What amount of protein comprises the feces of a domestic cat?

What amount of protein comprises the feces of a domestic cat?

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I've heard it said that the fecal excrement of cats, Felis catus, contains adequate amounts of protein so as to attract the interest of other animals e.g. dogs (Canis familiaris).

However, I am unable to locate any studies which reported the composition of a cat's feces as compared to those of any other animal with regards to a controlled quantity of proteins in the diet. I do see a lot of people on the internet making claims one way or the other, but never a citation to be seen.

Would anyone be interested in citing some references here so as to provide a more reputable resolution to this oft-repeated “fact”?
Unlikely as that would be, I'll post an answer here next time I check the university library.

Cat Breeds

Cats, which are part of the Felidae family, are some of the smallest carnivores that are protected by humans. Their retractable claws are incredibly useful, allowing them to maintain their balance, catch their prey, and protect themselves from threats. One of the telltale signs of a domestic cat is found in their skull, showing off sharp canine teeth that they inherited from their wild ancestors. With heightened hearing and smell, even cute cats can be resourceful hunters. They are one of the first animals to be domesticated.

The 13 Top Cat Characteristics Listed

Cats have unique characteristics of their physique, behavior, and even their senses. Though most people will know a domestic cat when they see one, here are some of the key ways that you can determine if an animal is definitively a cat.

  1. Warm-blooded mammals: Cat are in the mammal family, which means that they have many of the typical traits that are associated with this class. They have fur, they have a live birth, and they feed their young milk from their bodies as babies.
  2. Retractable claws: The cats of a cat are a rather unique feature of their paw. While they animal is relaxed, the claws remain concealed underneath the fur and skin. Rather than residing on the top of the toe, they are found around the toe pads to prevent them from wearing down as they walk. Typically, five claws are found on each of the front paws, but only four claws are found on the back paws.
  3. Lone hunters but social animals: When looking for their prey, the cat tends to seek out their prey on their own (though there is little need for hunting when owners will feed them). However, these animals prefer to surround themselves with other cats, humans, and even other animals, showing great affection. Plus, the mothers will typically be ferociously protective of their young.
  4. Verbal expression out of kittenhood: The vocal range of many mammals are minimal in adulthood, but the same is not true of cats. Their meow is biologically designed to mimic the sounds that a newborn baby makes, calling on the emotional reaction of their owners. Interestingly, this desire to attract the love of their owners can cause them to be rather jealous of any new kittens in the household.
  5. Live birth: The female cat will give birth to live young, which are called kittens. The kittens are often born in an amniotic sac, which is eaten by the mother. Kittens need to be nourished by their mothers until they are about 8 weeks old.
  6. Fast reflexes: Perhaps one of the most notable features of the cat is their ability to land on their feet. Even when falling from a height of nearly 10 feet, these animals will instinctively twist their body to land on their paws. The cat righting reflex is the same movement for any time that they fall, and they can correct their positioning in as little as 3 feet off the ground.
  7. Impressive night vision: The tapetum lucidum in the eye of the cat allows it to view anything in the dark, only requiring 15%-20% of the light that humans need to see the same. When the cat is taking in the most light, their pupils may expand to their entire exposed surface. As kittens, their eyes don’t even open until they are about a week old, though their vision may take longer to reach better focus.
  8. Minimum color vision: Though cats aren’t entirely colorblind, most cat are only able to see blue and yellow with clarity. The ability to see red and green is extremely limited.
  9. Heightened senses of hearing and smell: Cats can hear a tremendous range of sounds from 500 Hz to 32 kHz (Comparatively, the average person hears from 20 Hz to 15 kHz). The advanced sense of smell comes from the development of their olfactory bulb and mucosa. With a heightened pheromone sensitivity, this sense can impact their social and sexual behavior alike, despite their short snout.
  10. Sharp teeth: The ancestors of domestic cats significantly impacted their skull, offering a specialized jaw that includes two long canine teeth. These teeth are much smaller in domestic animals, as they don’t have to cat and kill their prey anymore. As sharp as the teeth are, their molars are hardly used for chewing food.
  11. Carnivorous: A cat’s diet is largely made of meat, requiring at least two grams of protein each day. This amount can vary with the weight and age of the cat. Although cats are carnivorous, many household plants and vegetables can be toxic if ingested.
  12. Digitigrade walking: Cat’s walk on all four legs, using their toes to keep their body balanced. The legs of each side of the body move together, which helps them to remain quiet as they hunt prey and avoid being detected.
  13. Hooked papillae on the tongue: The backwards-facing hooks of the tongue play an important role in a cat’s life, as it is used for self-grooming. Made of keratin (an important protein in hair), the fur will collect in the stomach and cause the cat to spit up their collected hair.

Fleas (Siphonaptera)

Cat Flea (Ctenocephalides felis)

The cat flea ( Fig. 10.9 ) occurs worldwide and is the most important flea pest of humans and many domestic animals. It is primarily a nuisance because it feeds not only on domestic and feral cats but also on humans, domestic dogs, and several livestock species. It also parasitizes wild mammals such as opossums and raccoons. This ectoparasite is the most common flea on dogs and cats in most parts of the world. Some strains of the cat flea appear to have adapted to ungulates such as horses or goats. Cases of severe anemia associated with huge numbers of cat flea bites have been recorded for these and other domestic animals.

Figure 10.9 . Cat flea, Ctenocephalides felis stacked image of cleared male.

Original image by Lorenza Beati and Lance A. Durden.

Female cat fleas typically produce larger numbers of fertile eggs if they take their blood meals from cats rather than other host species. Under optimal conditions, a female cat flea can lay about 25 eggs per day for a month, contributing to very high densities of fleas in a relatively short time. Adult cat fleas have well-developed genal and pronotal ctenidia ( Fig. 10.9 ) and can be distinguished from the dog flea (Ctenocephalides canis) by the longer head and longer first spine in the genal comb in Ctenocephalides felis.

Cat Facts: 7 Stops Along Your Cat’s Digestive System

The digestive system of the cat is a lot like ours. After all, we’re both mammals, and our organ structures are very similar. But there are some crucial differences because the cat evolved to be an obligate carnivore, while we humans can eat pretty much anything we want. Take a trip with me through your cat’s digestive system and find out what makes your cat tick.

1. The mouth

Typically a cat swallows her food in chunks rather than chewing: cat teeth don’t have flat chewing surfaces like ours, and cat jaws only move up and down, while ours can move from side to side to aid in the chewing of vegetables and other such material. The tongue positions the food for shredding and tearing and mixes it with saliva to start the breakdown of carbohydrates.

2. The esophagus

After the tongue pushes the food toward the throat, the muscles in this 12- to 15-inch-long tube move it down to the stomach.

3. The stomach

From the esophagus, the food passes through a sphincter (a ring of muscles) into the stomach itself. Here, acid begins the serious breakdown of food, particularly proteins. A cat’s stomach acid is strong enough to dissolve bones. The contractions of the stomach mix and grind food with secretions, turning it into a liquid before it passes to the next stage of digestion.

4. The duodenum and its pals: the liver and pancreas

From the stomach, the food slurry passes through another sphincter into the duodenum, the first part of the small intestine. Here, two things happen: the gall bladder releases bile and the pancreas releases several enzymes.

Bile, a chemical produced by the liver and stored in the gall bladder, breaks up large fat molecules into smaller ones that can be absorbed in the next stage of the digestive process. The enzymes secreted by the pancreas (which unfortunately does not appear in the illustration above) neutralize the acids in the food slurry before the mixture passes into the intestine, and aid in digestion of sugar, fat and protein. The best known of these is insulin, which regulates the levels of glucose in your cat’s body.

5. The small intestine

The small intestine is the longest part of the cat’s digestive system. All nutrients are absorbed there: the small intestine is lined with tiny bodies called villi, which absorb proteins, enzymes, electrolytes and water.

6. The large intestine

In the large intestine, also known as the colon, the last available water and electrolytes are absorbed from the food. Solid feces form and beneficial bacteria produce enzymes that break down material that is more difficult to digest.

7. The rectum and anus

Here, the formed feces collect until they’re ready to be ejected into the litter box. The transit time from mouth to anus is about 20 hours.

So, why does your cat go to the bathroom shortly after he eats? When food reaches the stomach and the digestive process begins, an "eject your cargo" signal is sent to the colon. This is called the gastrocolic reflex, and it’s why cats (and people) feel the urge to poop after they eat.

Do you have any other questions about the feline digestive system? Are there digestive disorders or conditions that you’d like me to explore? Ask away in the comments.

About JaneA Kelley: Punk-rock cat mom, science nerd, animal shelter volunteer, and all-around geek with a passion for bad puns, intelligent conversation, and role-play adventure games. She gratefully and gracefully accepts her status as chief cat slave for her family of feline bloggers, who have been writing their cat advice column, Paws and Effect, since 2003. JaneA dreams of making a great living out of her love for cats.


When considering a food for their CKD cats, many people focus on its phosphorus and protein levels, but it is also important to consider the calorie content, especially if you want your cat to maintain or gain weight and muscle.

A healthy cat needs approximately 30-35 calories per day per pound of body weight, or possibly more if the cat is particularly active. Your cat's nutritional needs (2006) National Research Council states that a lean adult cat weighing 5 lbs needs around 170 calories a day, and a lean adult cat weighing 10 pounds needs around 280 calories a day. The World Small Animal Veterinary Association Nutritional Assessment Guidelines make similar recommendations for the average healthy adult cat at a healthy weight.

This level of intake is unlikely to be sufficient for older cats. In Feeding older cats - an update in new nutritional therapies (2011) Sparkes A Topics in Companion Animal Medicine 26(1) pp37-42, Dr Sparkes states that older cats need more calories than younger cats, preferably in the form of protein. He adds that older cats also seem to do better when fed a diet containing prebiotics, antioxidants and essential fatty acids. Many sources, including the National Research Council, also believe that chronically sick cats need more calories, possibly as many as twice the number of calories as healthy cats.

Feline CKD therapeutic goals: do not throw away your shot (2018) Wooten SJ DVM360 Magazine reports "The most important thing to ponder about nutrition in feline CKD is whether the cat is eating enough, Dr. St. Denis says. This is more important than what the cat is eating. Maintaining adequate caloric intake and muscle mass is critical to avoid protein malnutrition. But, as you already know, ensuring adequate intake in a cat can be very challenging. Working with the client and providing education in this area is an important therapeutic strategy. If the cat isn't eating enough or is underweight, then Dr. St. Denis recommends feeding 1.2 to 1.4 times the resting energy requirement (RER). Most geriatric cats need at least 1.1 times RER."

So obviously, feeding a teaspoonful of food a day is not going to be enough to maintain your CKD cat's weight, let alone increase it if your cat is too thin. Another thing to consider is the water content of the food. Whilst most canned foods contain around 80% water, some are as high as 85% water. Although increased fluid content can be helpful for CKD cats, who are at risk of dehydration, the downside is that such foods may make the cat feel relatively full while providing insufficient calories for the cat's needs. This is often the case with simple foods that consist largely of meat or fish. Lower fat foods may also contain fewer calories.

As far as CKD is concerned, the goal is, as AJ Fascetti & S Delaney from the University of California at Davis say in Nutritional management of chronic renal disease , "Your pet needs to consume sufficient calories to supply essential nutrients, as well as to prevent the breakdown of their body's protein stores that will cause malnutrition and exacerbate the clinical signs of uremia."

ISFM consensus guidelines on the diagnosis and management of feline chronic kidney disease (2016) Sparkes AH, Caney S, Chalhoub S, Elliott J, Finch N, Gajanayake I, Langston C, Lefebvre H, White J & Quimby J Journal of Feline Medicine & Surgery 18 pp219-239 state "maintaining calorie intake is the highest priority in CKD."

Therapeutic kidney diets are more calorie dense than standard maintenance diets. You can check the calorie content of some US foods here (canned) and here (dry) .

Diagnostic and therapeutic approach to the anorectic cat (2001) Marks S Presentation to the World Small Animal Veterinary Association World Congress 2001 discusses feline dietary and calorie needs.

The ins and outs of managing feline chronic kidney disease Codi M Today's Veterinary Technician has a formula (Box 1) for calculating the daily energy requirement for neutered CKD cats.

4. Rearing and Testing Methodologies

The maintenance of C. felis colonies on cats or dogs is laborious and expensive. The use of large numbers of animals to rear and test potential flea products is also a concern of animal rights activists. Thus, artificial membrane testing and alternative rearing procedures are of special interest and the expanded use of these techniques could drastically reduce the need and costs for large numbers of laboratory animals. Various mammalian bloods, including bovine, ovine, porcine, and human, have been tested with artificial membrane feeding systems with varying degrees of success [192]. The use of EDTA as an anticoagulant resulted in increased numbers of flea eggs, but the percentage of eggs developing to adults was low. The highest egg production occurred when 25 ♂♂ and 100 ♀♀ were held together [192]. Considerably more research needs to be conducted with various laboratory strains and field-collected isolates of C. felis to better understand the limits and potential problems associated with membrane-fed flea populations. This research could provide tremendous cost savings and the need for laboratory animals.

C. felis maintained on rats consumed more blood, produced more eggs and had higher sex ratios of offspring than did those that were fed on mice. It is unclear if the lower numbers of fleas obtained were due to increased grooming by the mice [193]. A mass rearing method of C. felis was developed on mice in which C. felis females laid an average of 10.3 eggs/day which is considerably lower than female fleas maintained on cats. Adult C. felis survived for 㹀 days on the mice [194]. Another advantage is that sedated mice can be dosed with systemic insecticides and tested. Mice were dosed with active ingredients such as nitenpyram, cythioate, and fipronil and adult C. felis allowed to feed on them. Nitenpyram (1 mg/kg), cythioate (10 mg/kg), and fipronil (30 mg/kg) provided 㺔%, 64%, and 83% mortality, respectively. The mice might serve as a test model, possibly reducing the numbers of larger animals such as cats and dogs for systemic testing [195].

The WHO bioassay of exposing adult fleas to treated filter paper strips treated with insecticides has been the standard procedure used to detect insecticide resistance in fleas [196]. Franc and Cadiergues [197] reported the LD50’s of deltamethrin, permethrin, bioallethrin, and esbiothrin were 0.38, 230, 121, and 161 mg/m 2 , respectively. In a modified WHO test, the contact activity of insecticides applied to glass and nylon fabric substrates was compared with filter paper strips in adult flea exposures [198]. The nature of the substrate greatly affected the toxicity of insecticides such as carbaryl, malathion, permethrin and pyrethrum. Prior exposure of adult fleas to CO2 increased their susceptibility to insecticides, but circadian rhythms had no effect on toxicity [199].

The intrinsic activity of 13 different insecticides was tested against adult fleas by means of topical applications [200]. The test provided precise doses required to kill fleas, but requires considerable numbers of adult fleas and the laboratory maintenance of field-collected strains. A bioassay was developed to screen the potential activity of compounds against individual fleas in 96-well tissue culture plates. The bioassay distinguished between contact toxicity and insect growth regulator (IGR) effects [201]. Similarly, Chen et al. reported a contact and oral bioassay to test individual larva also using 96-well microliter plates [202]. In this bioassay, the laboratory strain was 2𠄴 times more susceptible to fipronil than the field isolate of C. felis tested, but there was no difference in susceptibility with imidacloprid or spinosad.

A larval bioassay was developed to determine the susceptibility of C. felis to imidacloprid utilizing flea eggs. The collection and shipment of flea eggs allowed the research team to collect field isolates from numerous clinics throughout 7 countries. Flea eggs were suspended over larval rearing medium and allowed to hatch thereby reducing the cannibalism of flea eggs [203]. To expedite the testing of large numbers of field-collected isolates a diagnostic dose of imidacloprid was determined to be 3 ppm [204]. This dose was robust enough to eliminate most isolates, but low enough to identify potential isolates for additional resistance testing. Topical applications of imidacloprid and fipronil to adults and exposure of larvae to treated media provided similar results for field-collected isolates and laboratory strains verifying the utility of the larval bioassay [205].

An improved bioassay technique was developed with treated filter paper strips to determine repellency of compounds to adult fleas. Deposits of 2% trans-cinnamaldehyde and 0.5% thymol repelled 97.6 and 90.6% of fleas for at least 8 h which was comparable to 15% DEET [206].


General principles

Absorption refers to the transfer of compounds from the gut lumen across the gut wall to the body tissues, including the lymph or blood of vertebrates and hemolymph of arthropods. At the cellular level, organic compounds can be absorbed from the gut lumen by paracellular and transcellular routes. Paracellular transport refers to movement between cells of the gut epithelium, while the transcellular route involves transport across the apical cell membrane of gut epithelial cells, transit across the cell (for some molecules with metabolic transformations in the cell), and then export at the basolateral membrane. We distinguish the term �sorption” (transport from gut lumen to body tissues by either the paracellular or transcellular route) from “uptake,” which refers to the transport from the gut lumen across the apical membrane of the gut epithelial cell (one step in transcellular transport).

This section considers absorption of organic compounds, particularly products of digestion: monosaccharides, the digestive breakdown products of complex carbohydrates peptide and amino acid products of protein digestion and lipids, SCFAs (generated by hydrolysis of triglycerides), and SCFAs (products of fermentative breakdown of complex carbohydrates by gut microbes). With the exception of SCFAs, these products are absorbed principally distal to the gastric region of the alimentary tract, for example, small intestine of vertebrates and midgut of insects. The absorptive cells are columnar epithelial cells called enterocytes. Exceptionally, SCFAs produced by the microbiota in the hindgut (e.g., mammalian colon and cecum) are absorbed across the hindgut wall by cells that are variously known as enterocytes, colonic enterocytes, or colonocytes.

In this section, two aspects of nutrient absorption are addressed: the modes of transport of the major classes of organic solutes and variation in nutrient absorption among animal taxa, in relation to nutritional habits and phylogeny and its mechanistic basis. Diet-related determinants of absorption in individual animals are addressed in Section “Matches of GI system biochemistry (enzymes, transporters) to changes in diet composition.”

Transcellular transport of organic solutes

Carrier-mediated transport

Most organic compounds absorbed across animal guts are polar, and their transport is predominantly or exclusively carrier-mediated, that is, mediated by membrane-bound transporters and displaying the twin characteristics of saturation kinetics and competitive inhibition. Two forms of carrier-mediated transport are recognized: facilitated diffusion, which is energy-independent and mediates transport down the electrochemical potential gradient and active transport, which is concentrative and dependent, directly or indirectly, on cellular energy. Simple diffusion, that is, down the concentration gradient and involving neither a carrier nor cellular energy, is an additional mode of absorption that is especially important for small, nonpolar molecules.

Absorption of carbohydrates

Monosaccharides cross the apical and basolateral membranes of gut epithelial cells by carrier-mediated mechanisms. The key glucose transporters in mammals and birds (184) are a Na+/glucose cotransporter SGLT1 (a member of the Na+/solute symporter family) and the facilitative transporter GLUT2, which transports glucose, fructose, mannose, and galactose with low affinity and N-acetyl-glucosamine with high affinity (444). Fructose is transported principally via the facilitative transporter GLUT5 (126). These transporters are expressed predominantly in the small intestine.

The expression of SGLT1 in the intestine is restricted to the apical membrane of enterocytes. Its capacity to take up glucose from very low concentrations in the intestinal lumen is driven by the downhill gradient of Na + ions maintained by the Na + /K + -ATPase on the basolateral membrane ( Fig. 9 ) (206). Once in the cell, the glucose is widely accepted to be transported down its concentration gradient across the basolateral membrane into the circulation by GLUT2. Under conditions of high luminal glucose content, however, GLUT2 in rodents is inserted into the apical membrane, where it mediates the high flux of glucose into the enterocyte (254). Some data suggest that sugar-induced translocation of GLUT2 may not occur universally in mammals (18, 330), and further research is required to establish the distribution of this effect with respect to phylogeny and diet.

Transport of glucose and fructose across the mammalian enterocyte by SGLT1, GLUT2, and GLUT5. The insertion of GLUT2 into the apical membrane is mediated by the detection of luminal glucose by the TIR2/3 receptors and Ca 2+ signaling, as described in text.

The mechanism by which GLUT2 is inserted into the apical enterocyte membrane is understood in outline (253). Under high glucose conditions, the inward flux of Na + ions via SGLT1 results in depolarization of the membrane and Ca 2+ influx, which, in turn, causes a large-scale reorganization of the cytoskeleton, facilitating access of proteins to the apical membrane. In parallel, high concentrations of luminal glucose and fructose activate the TIR2/3 receptor on the apical membrane, resulting in trafficking of phospholipase (PLC)㬢 and protein kinase C (PKC)βII to the apical membrane. Diacylglycerol generated by PLC㬢, together with the high Ca 2+ , activates PKCβII, permitting the insertion of GLUT2 into the apical membrane and the resultant high capacity uptake of glucose and fructose. This process occurs very rapidly.

In the mouse, the responsiveness of GLUT2 insertion to luminal sugars varies among sugars, being triggered much less efficiently by glucose and complex sugars than by fructose, sucrose, and a mixture of glucose and fructose (193) mice fed on a high-fructose diet have been reported to bear GLUT2 permanently on the apical membrane of enterocytes (434). Artificial sweeteners, such as sucralose, dramatically increase GLUT2 insertion and the resultant uptake of glucose, such that the sugar is absorbed efficiently from lower concentrations in the presence of the artificial sweetener than in its absence (302). The implications of these rodent studies for human nutrition are not yet fully resolved.

Phylogenetic analysis assigns the mammalian GLUT2 to a clade that includes three further mammalian GLUTs (GLUT1, 3, and 4) and invertebrate, but no nonmetazoan, GLUTs, suggesting that this group of transporters may have evolved in the basal metazoans or immediate ancestors of animals (472). There is also evidence that SGLT1 and GLUT transporters contribute to intestinal glucose absorption in nonmammalian vertebrates, including fish (72, 269). The molecular basis of sugar uptake across the gut wall has not, however, been investigated widely in the invertebrates. Among insects, glucose transport across the midgut of the hymenopteran parasite Aphidius ervi is mediated by a SGLT1-like transporter on the apical membrane, together with a GLUT2-like transporter on both the apical and basolateral membranes of the enterocytes and a second passive transporter similar to GLUT-5 is implicated in fructose uptake (58). There is also persuasive molecular and physiological evidence for the involvement of SGLT and GLUT transporters in glucose absorption from the midgut of the pyrrochorid bug Dysdercus peruvianus, with K + , not Na + , as the likely counterion of SGLT (28). This condition is not, however, universal among insects. For example, genome annotation of the pea aphid Acyrthosiphon pisum revealed no Na + /solute symporter with plausible specificity for sugars, but 29 candidate sugar transporters in the MFS family, equivalent to GLUT (368). These included an abundantly expressed gene ApSt3, a hexose uniporter with specificity for glucose and fructose in the distal midgut. Aphids may not, however, be typical of insects because their diet of plant phloem sap is sugar rich, and a concentration gradient from gut lumen to epithelial cell and hemocoel is maintained by the excess sugar in the gut lumen (127).

Pathways for amino acid and peptide absorption

The products of protein digestion taken up by enterocytes of the mammalian intestine are free amino acids, dipeptides, and tripeptides. Free amino acids are taken up from the small intestine of mammals by multiple carriers with overlapping specificities, with the result that most individual amino acids are transported by more than one transporter. By contrast, peptides are taken up by a single transporter with very low selectivity, as considered at the end of this section.

The amino acid transporters are classified by their activity (specificity and kinetics) into multiple systems, and by sequence homology into solute carrier (SLC) families. The SLC nomenclature was devised by the Human Genome Organization for transporters in the human genome (with all members of each family having 㸠%�% amino acid sequence homology), and is widely used for other animals. The principal transporters mediating amino acid transport in the human intestine are summarized in Table 3 .

Table 3

Amino Acid Transport Systems in the Mammalian Intestine [Data From Table 1 of Reference (41)]

System a Solute carrier
(SLC) group
Amino acids
transported c
Transport propertiesLocation
Neutral amino acids (AA 0 )
B 0 B 0 AT1SLC6A19All AA 0 AA 0 /Na + symportApical
ASCASCT2SLC1A5A, S, C, T, QAA 0 antiporter (no net AA 0 uptake of
L4F2hc/LAT2 2 SLC3A2/SLC7A8All AA 0 except PNa + independent transportBasolateral
Cationic amino acids (AA + )
b 0,+ rBAT/b 0,+ AT b SLC3A1/SLC7A9R, K, O, cystineAA + or cystine (uptake)/AA 0 (efflux) antiportApical
y + L4F2hc/y + LAT1 b SLC3A2/SLC7A7K, RAA + (efflux)/AA 0 antiportBasolateral
4F2hc/y + LAT2 b SLC3A2/SLC7A6K, R, C
Anionic amino acids (AA − )
X − AGEAAT3SLC1A1E, DAA − /3Na + symportApical
Proline and glycine
IMINOIMINOSLC6A20P, HO-PP/Na + symportApical
PATPAT1SLC36A1P, G, AP or G/H + symport d

Studies on human, rodent and rabbit suggest that the amino acid transporters in the mammalian small intestine can be assigned to four groups, mediating the transport of neutral, cationic, anionic, and imino acids, respectively (41). Uptake across the apical membrane is mediated by: Na + -coupled transporters, for example, the B 0 transporter with broad specificity for neutral amino acids and found in all parts of the small intestine proton-motive force, as in the uptake of proline and glycine by the transporter PAT and amino acid exchange, for example, uptake of cationic amino acids and cystine linked to efflux of neutral amino acids by b 0,+ system. Transport across the basolateral membrane is also mediated by amino acid exchange, for example, y + L for efflux of cationic amino acids, or by facilitative diffusion, for example, transporters of the L and T system for efflux of neutral and aromatic amino acids, respectively.

The rich classical literature on the kinetics of amino acid transport across the intestinal epithelium of various nonmammalian vertebrates and invertebrates is summarized by (246) and (341), and there is increasing interest in analysis from a molecular perspective [e.g., for birds, see reference (184)]. The midgut amino acid transporters that have been studied in insects belong principally to the Na + -coupled symporter family SLC6. As in mammals, multiple transporters are expressed, with overlapping specificities for amino acids. Some are very specific, for example, NAT6 and NAT8 in the distal midgut of mosquito Anopheles gambiae transport just aromatic amino acids (318, 319). Other SLC6 transporters have a very broad range. Notably, the neutral amino acid transporter in Drosophila (DmNAT6) can mediate the transport of most amino acids apart from lysine, arginine, aspartate, and glutamate and, remarkably, it can also take up D-isomers of several amino acids (321). This capability can be linked to the abundance of D-amino acids in the cell walls of bacteria, which are an important component of the natural diet of Drosophila species. DmNAT6 is an active transporter, capable of mediating uptake against the concentration gradient.

Exceptionally, amino acid transport in the midgut of larval Lepidoptera is coupled to K + ions, and not Na + ions (158, 340). This trait is believed to be linked to the high K + /low Na + conditions in the gut of these insects, which eat plants with high ratios of K + /Na + . Multiple transporters are involved with a range of specificities, including two neutral amino acid transporters in Manduca sexta (KAAT1 and CAATCH1), both members of the SL6 family (71, 145) with distinctive amino acid selectivities (322). The cotransport of the K + ions and amino acid into enterocytes is coupled to the ATPase-dependent extrusion of K + ions from adjacent goblet cells. The coupled functions of electrogenic K + transport and K + /amino acid uptake are mediated by different cells, presumably because the high emf generated by the goblet cells could compromise the function of the SL6 and other transporters.

Amino acid transporters are also expressed in the apical membrane of the insect hindgut epithelium, where they mediate the uptake of amino acids in the primary urine produced in the Malpighian tubules. For example, glycine, serine, alanine, and threonine are actively resorbed into the cells of the rectal pads of the locust by a Na + cotransporter of the SLC6 family (430). Proline is also taken up, and is a major respiratory substrate of rectal cells (76).

Returning to mammals, a single proton-oligopeptide transporter, PEPT1 (member of SLC15A family) mediates the uptake of peptides across the apical membrane ( Fig. 10 ). It can transport thousands of di- and tripeptides with low affinity and high capacity, but neither free amino acids nor tetrapeptides (106). This property is intelligible from the structural features of the binding pocket of the protein, which can accommodate compounds with oppositely charged head groups (carboxyl and amino groups) separated by a carbon backbone of 0.55 to 0.63 nm (compatible with di-/tripeptides) and a capacity to accommodate a great variety of size and charge in the side groups (125). The acid load of the enterocyte imposed by H + influx associated with PEPT1-mediated peptide/H + symport is relieved by Na + /H + exchange at the apical membrane (170). (Early reports that peptide transport is Na + -linked are erroneous.) Neutral and most cationic peptides are cotransported with one proton, while anionic peptides require two protons (228). Peptides taken up into the enterocyte are hydrolyzed by a diversity of cytoplasmic peptidases ( Fig. 10 ), and the resultant amino acids are exported via transporters on the basolateral membrane ( Table 3 ).

Peptide absorption. Uptake of di- and tripeptides across the apical membrane of enterocytes is mediated by PEPT1/H + symport, with the H + transport coupled to the Na + /H + antiporter NHE3. The peptides are hydrolyzed by multiple cytosolic hydrolases, and the resultant amino acids are exported via the basolateral membrane by multiple transporters (see Table 3 ). The efflux of unhydrolyzed peptides across the basolateral membrane is mediated by peptide transporters that have not been identified at molecular level.

Low-affinity/high-capacity peptide transporters expressed in the alimentary tract have been characterized functionally in nonmammalian vertebrates, notably the chicken (184), zebrafish (454), and other fish (455), and in Caenorhabditis elegans (317) and Drosophila (382). The peptide transporter family to which the mammalian PEPT1 protein belongs is ancient, with the defining peptide transporter motif (PTR) motif evident in proteins of bacteria, fungi, plants, and animals (107). Analysis of basal animal groups is required to establish the evolutionary origin(s) of gut-borne peptide transporter(s) in metazoans.

Of central importance is the relative importance of peptide and amino acid uptake in the protein nutrition of the animal. Humans with mutational defects in amino acid uptake systems do not suffer from essential amino acid deficiencies, for example, abolition of cystine uptake caused by defect in b 0,+ system (condition known as cystinuria), and aromatic amino acid uptake by defect in B 0 system (Hartnup disease) and this suggests that PEPT1-mediated uptake of peptides can be substantial, sufficient to meet the dietary requirements for these essential amino acids (106). The significance of PEPT1 for the protein nutrition of other animals remains to be established.

Transcellular pathways for lipid absorption

In vertebrates, the absorption of lipid hydrolysis products and sterols is dependent on their incorporation into micelles formed in the lumen of the small intestine. Micelles are 4 to 8 nm diameter aggregations of the hydrophobic lipid products with bile acids, which act as amphipathic detergents and mediate the passage of the lipid products across the aqueous boundary layer to the apical membrane of intestinal enterocytes. A proportion of the micelle-associated molecules pass across the apical membrane by simple diffusion, according to the concentration and permeability coefficient of each compound, but carrier-mediated transport is also involved.

The dominant lipids in most diets are triacylglycerols (TAGs), accompanied by small amounts of various polar and nonpolar lipids, including phospholipids, sterols, and the fat-soluble vitamins A and E. The products of lipid digestion include free FAs, glycerol, monoglycerides, and lysophospholipids. Following uptake by diffusion and via transporters, these products are transported to the endoplasmic reticulum, where they are used to synthesize diacylglycerols (DAGs), TAGs, phospholipids, cholesterol esters, etc. They are then packaged with lipoproteins to form chylomicrons, which are passed through the Golgi apparatus for exocytosis. In mammals, the chylomicrons are delivered to the lymphatic vessels. The mechanism of chylomicron assembly is reviewed by reference (227).

Of particular note are the transporters mediating sterol flux across the apical membrane of enterocytes. In mammals, a steep diffusion gradient across the apical membrane is generated by acyl-CoA:cholesterol acyltransferase (ACAT2)-mediated esterification of cholesterol in the enterocyte ( Fig. 11 ), and it used to be assumed𠅎rroneously—that cholesterol is taken up exclusively by simple diffusion. There is now overwhelming physiological and molecular evidence for carrier-mediated uptake and also efflux across the apical membrane ( Fig. 11 ). The key transporter mediating cholesterol uptake is Niemann Pick C1-like 1 (NPC1L1) protein, identified initially as the transporter sensitive to ezetimibe, a highly specific and potent inhibitor of intestinal cholesterol absorption (6, 111, 234). However, overexpression of NPC1L1 in nonenterocyte cells has not yielded cholesterol transport activity, suggesting that additional proteins may be required to reconstitute a fully functional cholesterol transporter. NPC1L1 has 50% amino acid homology to the NPC1 protein, which functions in intracellular cholesterol trafficking and is defective in the Niemann Pick type C cholesterol storage disease (70). Importantly, cholesterol is also exported across the apical membrane, via the ATP-binding cassette (ABC) transporters ABCG5 and ABCG8 (24). ABC transporters generally have 12 transmembrane domains, but each of ABCG5 and ABCG8 has just six transmembrane domains transport activity is mediated by the heterodimer, comprising a 12-transmembrane protein complex (194). Cholesterol molecules that are not esterified in the endoplasmic reticulum are eliminated from the enterocyte to the intestinal lumen and voided via the feces.

Absorption of cholesterol in mammalian intestine. Cholesterol presented in micelles to the apical membranes of enterocytes is taken up by Niemann-Pick C1-like-1 (NPC1L1) transporter, and esterified by acyl-CoA:cholesterol acyltransferase (ACAT2), an enzyme in the endoplasmic reticulum membrane. These esterified products are incorporated into apolipoprotein (apo)B48-containing chylomicrons in a microsomal triglyceride transport protein-dependent manner. After further processing, the chylomicrons are released from the basolateral membrane by exocytosis. Nonesterified sterol is eliminated into the gut lumen via ATP-binding cassette (ABC) transporters ABCG5 and ABCG8.

Nevertheless, ABCG5/G8 does not function exclusively in relation to cholesterol. Mammals feeding on fungal or plant material need to process the dominant sterols in these foods: ergosterol and phytosterols, respectively. These sterols have the tetracyclic ring structure and side chain at C17, as in cholesterol, but the side chain in phytosterols is alkylated at C-24 (e.g., with ethyl substituent in sitosterol), and some phytosterols (e.g., stigmasterol) also have double bonds in the side chain. They are taken up by NCP1L1 into enterocytes, but they are not esterified by ACAT2 and are eliminated via ABCG5/G8. Wang (2007) has described ABCG5/G8 as “the gatekeeper to avoid high plant sterols in plasma." This role is illustrated vividly by patients with mutations in ABCG5/G8, resulting in elevated absorption and plasma levels of sitosterol, a condition known as sitosterolemia. In healthy individuals, dietary phytosterols reduce serum cholesterol levels, probably through their more efficient incorporation than cholesterol into micelles, resulting in reduced cholesterol uptake (223) this is why sitosterol is sold as a functional food. A dietary supply of cholesterol is not required by mammals, which can synthesize sterols de novo.

Among invertebrates, most research on lipid absorption has concerned insects. The products of insect lipid digestion are absorbed principally across the midgut epithelium, although absorption in the foregut, e.g. the crop of the cockroach Periplaneta americana, can also occur (63, 447). Lipid absorption in insects differs from vertebrates in several important respects. (i) Although, as in vertebrates, the products of lipid hydrolysis are packaged into micelles, the amphipathic molecules of insect micelles are fatty acid-amino acid, lysophospholipid, and glycolipid complexes (442), and not bile acids (which insects lack). (ii) The lipids synthesized in all insect enterocytes studied to date are dominated by DAGs, not TAGs and sterols appear to be absorbed without esterification in the enterocyte (442). (iii) The functional equivalent to chylomicrons in insects is the high-density lipoprotein, lipophorin, which mediates the transport of DAGs exported from enterocytes (9). Unlike chylomicrons, lipophorin is not synthesized in enterocytes it is localized in the hemolymph (blood), where it acts as a shuttle delivering lipids to the fat body and other organs. Lipophorin has been implicated in the transport of hydrocarbons, carotenoids, sterols, and phosopholipids, as well as DAGs. (iv) The role of transporters in the absorption of lipidic compounds in insects is poorly studied, although a NPC-like transporter, NPC1b, has been demonstrated to mediate sterol uptake from the midgut of Drosophila (456), and a fatty acid transporter on the apical membrane has been invoked (63).

The products of lipid digestion in the gut of the spider Polybetes phythagoricus are taken up by cells of the midgut diverticulum, where they are processed to TAGs and phospholipids and exported via two distinct carriers: a high-density lipoprotein (equivalent to the insect lipophorin) and a very high density lipoprotein that also contains hemocyanin (275).

Pathways for absorption of short chain fatty acids

This class of lipid-related molecules is distinctive from other lipids in two important respects. First, they have lower hydrophobicity than long-chain fatty acids. Consequently, SCFAs permeate membranes more slowly by simple diffusion, and cellular transport mechanisms are especially important for SCFA absorption. Second, they are waste products of fermentative respiration of resident bacteria in nongastric, anoxic regions of the alimentary tract (not products of animal digestion), with the implication that they are produced and absorbed across the hindgut (and pregastric fermentation chambers of some animals, see Section �sic designs of digestive tracts”), not midgut, small intestine etc. For example, in humans, acetate, propionate, and butyrate are produced in the ratio 3:1:1 and contribute up to 10% of respiratory fuel butyrate is particularly important, as the primary carbon source for colonocytes (156). Topics not considered here are the role of SCFAs in the regulation of fluid and electrolyte movement of the vertebrate gut, reviewed by reference (32), and importance of butyrate in the regulation of colonic cell proliferation and differentiation [see review of reference (198)].

SCFAs are transported across the colon wall of mammals by a combination of simple diffusion and carrier-mediated processes. The SCFA transporter(s) have yet to be identified definitively. Studies with colonic epithelial tissue and luminal perfusion experiments point to SCFA/HCO3 − exchangers, with evidence for saturation kinetics and competitive inhibition by acetate, butyrate, and propionate, but not lactate (203, 204, 312, 378). However, the transport proteins responsible for SCFA/HCO3 − exchange have yet to be identified, raising the possibility that SCFA is coupled to HCO3 − via multiple transporters, for example, SCFA/H + cotransport and Cl − /HCO3 − exchange (99). SCFAs are transported by the H + /monocarboxylate transporter MCT1 in several colonic cancer cell lines, including Caco-2 cells, (282) and by a Na + -dependent SCFA transporter, SLCA8, cloned from the human intestine (324), but the relevance of these transporters to SCFA transport in the colon and cecum of healthy mammals in vivo is uncertain.

The fate of SCFAs in the gut epithelium has been studied particularly in the rumen. A proportion of the SCFAs taken up is metabolized to lactate and ketonic acids (including acetoacetate and 3-hydroxybutyrate) these products are transported from the basolateral membrane of epithelial cells, probably via MCT1, to the blood. The intraepithelial metabolism of SCFAs contributes to the high-energy demands of these cells. Additional advantages are the maintenance of the concentration gradient between the lumen of the rumen and epithelial cell contents, so promoting sustained SCFA uptake, and the greater solubility of the products (lactate etc.) than SCFAs, and therefore, facilitating transport in the blood to other organs.

Paracellular transport of organic molecules

Paracellular transport across the gut is constrained by tight junctions at the apical end of the lateral membrane of all cells in the epithelium. Tight junctions have selective permeability, discriminating among solutes by charge and size. Two pathways across the tight junction have been identified in various epithelial cell types, including gut epithelia: a high-capacity pore pathway, permeable to small uncharged molecules and ions (π.8 nm diam.) and a leak pathway mediating low capacity flux of larger, uncharged molecules. Caco-2 cells display a third pathway that allows the passage of molecules up to 0.13 nm diameter, suggesting an additional route in the mammalian gut intestine (448). Although the contribution of the various tight junction proteins to the restriction of movement between epithelial cells is not fully understood, there is growing evidence that: (i) the claudins (a family of membrane proteins spanning the tight junction) play a crucial role in the pore pathway, with individual family members forming cation- or anion-selective pores (ii) two further tight junction proteins, occludin and zona occludens-1, are important in the leak pathway and (iii) various intracellular and extracellular signals mediate cross-talk between the two pathways, resulting in dynamic regulation of flux of different classes of compounds by the paracellular route. For an excellent review on the molecular determinants of the function and plasticity of tight junctions, the reader is referred to (398).

For humans and biomedical rodent models, the paracellular pathway makes a negligible contribution to absorption of many solutes. Despite the growing evidence for dynamic selective permeability of tight junctions, the predominance of transcellular transport has been attributed to the superior selectivity of transcellular transport via carrier-mediated transporters on the apical membrane of enterocytes, thereby protecting the animal from many toxins or otherwise deleterious compounds breaching the gut wall.

Nevertheless, there is substantial evidence for extensive paracellular transport of solutes in flying birds and fruit bats. Particular insight into the mode of sugar transport comes from parallel analysis of absorption of L-glucose (the stereoisomer that does not interact with the glucose transporters and is transported exclusively by paracellular route), and D-glucose or 3-O-methyl-d-glucose (3OMD-glucose), a nonmetabolizable analogue of D-glucose that can be transported into cells. Karasov and colleagues measured total absorption (mediated and passive) of D-glucose or 3OMD-glucose and passive absorption of L-glucose in intact animals by a standard pharmacokinetic methodology, for example, references (78, 244, 278, 280). In experiments conducted on avian species, the fractional absorption of D-glucose and 3OMD-glucose did not differ significantly and L-glucose was found to account for the majority (range 50 to > 90%) of glucose absorption (79, 238, 316) ( Fig. 12 ). In analogous studies in rats (443), dogs (277), and humans (154) L-glucose, and hence passive absorption, is quantitatively much less important, confirming the likely phylogenetic difference between birds and mammals in the importance of paracellular transport.

Paracellular absorption of glucose in the American robin (Turdus migratorius) investigated by pharmacokinetic methodology, using D-glucose, L-glucose (the glucose stereoisomer that is not be transported across the intestinal membrane), and 3-O-methyl- d -glucose (3OMD-glucose, a nonmetabolizable but actively transported analogue of D-glucose). (A) The dose-corrected plasma concentration of [ 3 H]L-glucose as a function of time since American robins were injected (unfilled symbols) or gavaged (filled symbols) with the probe solution containing L-glucose. The areas under the curves (AUCs) are used to calculate fractional absorption, f, which averaged 87 ± 3%. (B) Time course of absorption of [ 3 H]L-glucose, and [ 14 C]D-glucose and 3OMD-glucose. Over early time points, the amounts of L-glucose absorbed was 50% to 70% of the amounts of D-glucose absorbed, which was interpreted to mean that the majority of glucose was absorbed by the paracellular pathway. Adapted from Figures 1 and ​ and2 2 from reference (316), with permission.

Intestinal paracellular absorption in nonflying mammals and birds appears to be qualitatively similar in regards to molecular size selectivity, as characterized using a series of nonelectrolyte water-soluble probes that differ in molecular dimension (80, 199) and in charge selectivity as characterized using relatively inert charged peptides (81, 205). Quantitatively, paracellular absorption is at least twice greater in small birds (< 400g) than in nonflying mammals ( Fig. 13A ), with the difference declining with increasing body size (278).

(A) Fractional absorption of water soluble carbohydrates by intact birds (triangles, solid line) and nonflying eutherian mammals (circles, dashed line). Arabinose, rhamnose, cellobiose, and lactulose are inert, nonactively transported compounds whereas 3-O-methyl- d -glucose is not metabolized but is transported actively as well as passively absorbed. Fractional absorption of the passively absorbed probes declined with increasing molecule size and differed significantly between the two taxa, although the difference diminished with increasing molecule size. In contrast, absorption of 3-Omethyl- d -glucose did not differ significantly between the taxa. The interpretation is that species in both groups absorb most glucose, but that birds relied more on the passive, paracellular route. Figure 4A adapted, with permission, from reference (243). (B) Small intestine nominal (smoothbore tube) surface area in omnivorous birds and mammals (same symbols and lines as in A). There was no significant difference in slope between birds and nonflying mammals (n = 46 species and 41 species in birds and mammals, respectively). When the lines were fit to the common slope of 0.73, the calculated proportionality coefficients (intercept at unity) were significantly lower for birds than for mammals. Hence, small intestine nominal surface area in birds is 36% lower than that in nonflying mammals. Figure 4B adapted from reference (75).

The difference in paracellular absorption between birds and nonflying mammals is not simply explained by mediated absorption in birds of the carbohydrate probes that are presumed to be absorbed passively. In studies using radiolabeled L-glucose and L-arabinose, their uptake by intestine in vitro was not significantly inhibited by high concentrations (50� mmol/L) of unlabeled L-glucose, L-arabinose, L-rhamnose, or D-glucose (280), which makes it unlikely that their absorption is carrier mediated. Nor is the difference in paracellular absorption between birds and nonflying mammals explained by longer retention of digesta in the gut of the former relative to the latter. Avian species typically have shorter mean retention time of digesta than do similar sized nonflying mammalian species (315). Because birds typically achieve higher paracellular absorption with less intestinal length and surface area than do similar sized nonflying mammals, there apparently are differences in intestinal permeability per unit intestinal tissue. This was confirmed in a comparison of pigeons and laboratory rats. Under similar recirculating duodenal perfusion conditions, anesthetized rats, and pigeons absorbed D-glucose at a comparable rate but pigeons had significantly greater (Ϣ× higher) absorption of inert carbohydrate probes (280). The difference in paracellular solute absorption between mammals and birds cannot be linked to differences in solvent drag because it is so difficult (155) to distinguish between water absorbed by the paracellular route versus aquaporins, which occur in intestine of both mammals and birds (229).

Enhanced paracellular absorption may have evolved as a compensation for smaller intestinal size in birds compared with nonflying mammals ( Fig. 13B ). In a phylogenetically informed allometric analysis, flying birds had shorter intestines and about 36% less nominal small intestine surface area (area of a smooth bore tube) as compared with nonflying mammals (279). Small intestine volume, a direct function of tube length and area, and consequently the potential mass of digesta carried, was relatively smaller in birds, by 32%. The difference in intestinal surface area between birds and nonflying mammals did not depend on diet in the analysis. (Diet did have a significant effect on gut size, but the effect was on cecal and large intestine size.) Another advantage of paracellular absorption is that it is an energetically cheap way to match absorption rate to substrate concentration in the diet and lumen.

If there has indeed been natural selection for smaller intestinal size in fliers, and increased paracellular absorption as a compensation, then one might expect to find the same patterns found in flying birds versus nonflying mammals in a comparison within mammals between fliers (i.e., bats) and nonfliers. Preliminary evidence suggests that this is the case (75), but more extensive sampling is necessary.

Dietary and phylogenetic correlates of transporter activity

Generally, in vertebrates, the more carnivorous the species, the lower its rate of intestinal mediated glucose absorption (246). This pattern, first described in a survey of more than 40 species drawn from the major vertebrate classes (245), is apparent also in comparative studies within fish (51) and birds (247). Based on phlorizin-binding studies in a limited number of species, it appeared that species differences in tissue-specific glucose uptake may largely reflect species differences in the number of copies of the main apical membrane glucose transporter SGLT1, although it is possible that differences in turnover time of the transporter can also contribute (150).

There was no marked pattern of higher intestinal transport activity for amino acids among the more carnivorous vertebrate species (245, 246). Likewise for digestive enzymes, it seems typical to find significant positive relationships between carbohydrases and dietary carbohydrate but not between proteases/peptidases and dietary protein, at least for fish (179), and in birds (261). This is perhaps expected because all animals, regardless of diet, need protein and so there should not be strong selection for very low protein processing capability in animals. In addition, it has been argued (214) that it would be advantageous for herbivores with relatively rapid gut throughput to have compensatorily higher biochemical capacity to process proteins and recover them rather than excrete them.

Antibacterial drugs


Fluoroquinolones are rapidly absorbed after oral administration in monogastric animals absorption is complete (80–100%) for enrofloxacin, less so for ciprofloxacin (50–70%) and norfloxacin (40%). Administration with food may delay the time to peak plasma concentration but does not alter the concentration achieved. Administration with compounds that contain metal ions will adversely affect plasma fluoroquinolone concentrations.

Low protein binding, low ionization and high lipid solubility result in large volumes of distribution and good penetration into CSF, bronchial secretions, bone, cartilage and prostate. Concentrations achieved in respiratory and genitourinary tract secretions are higher than plasma concentrations and prostatic concentrations may be 2–3 times higher than in plasma.

The major metabolite of enrofloxacin is ciprofloxacin but the amount of ciprofloxacin produced varies between and within species. Elimination may be renal, hepatic or both, depending on the drug. Enrofloxacin undergoes predominantly renal elimination, for difloxacin it is fecal and marbofloxacin is excreted in both urine and feces.

The elimination half-life varies with the drug but is usually sufficiently long (8–12 h) to permit once-daily dosing. A postantibiotic effect (continued suppression of bacterial growth following removal of the drug) of a few minutes to several hours occurs with fluoroquinolones against most Gram-negative and some Gram-positive bacteria. The duration of the postantibiotic effect depends on the pathogen, the concentration of the drug above MIC and the duration of exposure.

Urinary drug concentrations are substantially in excess of MIC values for virtually all susceptible pathogens, exceeding plasma concentrations by several hundred times and remaining high for 24 h after administration.

Toxoplasmosis: General FAQs

Toxoplasmosis is an infection caused by a single-celled parasite called Toxoplasma gondii. While the parasite is found throughout the world, more than 40 million people in the United States may be infected with the Toxoplasma parasite. The Toxoplasma parasite can persist for long periods of time in the bodies of humans (and other animals), possibly even for a lifetime. Of those who are infected however, very few have symptoms because a healthy person&rsquos immune system usually keeps the parasite from causing illness. However, pregnant women and individuals who have compromised immune systems should be cautious for them, a Toxoplasma infection could cause serious health problems.

How do people get toxoplasmosis?

A Toxoplasma infection occurs by one of the following:

  • Eating undercooked, contaminated meat (especially pork, lamb, and venison) or shellfish (for example, oysters, clams or mussels).
  • Accidental ingestion of undercooked, contaminated meat or shellfish after handling them and not washing hands thoroughly (Toxoplasma cannot be absorbed through intact skin).
  • Eating food that was contaminated by knives, utensils, cutting boards and other foods that have had contact with raw, contaminated meat or shellfish.
  • Drinking water contaminated with Toxoplasma gondii.
  • Accidentally swallowing the parasite through contact with cat feces that contain Toxoplasma. This might happen by
    • Cleaning a cat&rsquos litter box when the cat has shed Toxoplasma in its feces
    • Touching or ingesting anything that has come into contact with cat feces that contain Toxoplasma or
    • Accidentally ingesting contaminated soil (e.g., not washing hands after gardening or eating unwashed fruits or vegetables from a garden).
    • Mother-to-child (congenital) transmission.
    • Receiving an infected organ transplant or infected blood via transfusion, though this is rare.

    What are the signs and symptoms of toxoplasmosis?

    Symptoms of the infection vary.

    • Most people who become infected with Toxoplasma gondii are not aware of it because they have no symptoms at all.
    • Some people who have toxoplasmosis may feel as if they have the &ldquoflu&rdquo with swollen lymph glands or muscle aches and pains that may last for a month or more.
    • Severe toxoplasmosis, causing damage to the brain, eyes, or other organs, can develop from an acute Toxoplasma infection or one that had occurred earlier in life and is now reactivated. Severe toxoplasmosis is more likely in individuals who have weak immune systems, though occasionally, even persons with healthy immune systems may experience eye damage from toxoplasmosis.
    • Signs and symptoms of ocular toxoplasmosis can include reduced vision, blurred vision, pain (often with bright light), redness of the eye, and sometimes tearing. Ophthalmologists sometimes prescribe medicine to treat active disease. Whether or not medication is recommended depends on the size of the eye lesion, the location, and the characteristics of the lesion (acute active, versus chronic not progressing). An ophthalmologist will provide the best care for ocular toxoplasmosis.
    • Most infants who are infected while still in the womb have no symptoms at birth, but they may develop symptoms later in life. A small percentage of infected newborns have serious eye or brain damage at birth.

    Who is at risk for developing severe toxoplasmosis?

    People who are most likely to develop severe toxoplasmosis include:

    • Infants born to mothers who are newly infected with Toxoplasma gondii during or just before pregnancy.
    • Persons with severely weakened immune systems, such as individuals with AIDS, those taking certain types of chemotherapy, and those who have recently received an organ transplant.

    What should I do if I think I am at risk for severe toxoplasmosis?

    If you are planning to become pregnant, your health care provider may test you for Toxoplasma gondii. If the test is positive it means you have already been infected sometime in your life. There usually is little need to worry about passing the infection to your baby. If the test is negative, take necessary precautions to avoid infection (See below).

    If you are already pregnant, you and your health care provider should discuss your risk for toxoplasmosis. Your health care provider may order a blood sample for testing.

    If you have a weakened immune system, ask your doctor about having your blood tested for Toxoplasma. If your test is positive, your doctor can tell you if and when you need to take medicine to prevent the infection from reactivating. If your test is negative, it means you need to take precautions to avoid infection. (See below).

    What should I do if I think I may have toxoplasmosis?

    If you suspect that you may have toxoplasmosis, talk to your health care provider. Your provider may order one or more varieties of blood tests specific for toxoplasmosis. The results from the different tests can help your provider determine if you have a Toxoplasma gondii infection and whether it is a recent (acute) infection.

    What is the treatment for toxoplasmosis?

    Once a diagnosis of toxoplasmosis is confirmed, you and your health care provider can discuss whether treatment is necessary. In an otherwise healthy person who is not pregnant, treatment usually is not needed. If symptoms occur, they typically go away within a few weeks to months. For pregnant women or persons who have weakened immune systems, medications are available to treat toxoplasmosis.

    How can I prevent toxoplasmosis?

    There are several steps you can take to reduce your chances of becoming infected with Toxoplasma gondii.

    • Cook food to safe temperatures. A food thermometer should be used to measure the internal temperature of cooked meat. Color is not a reliable indicator that meat has been cooked to a temperature high enough to kill harmful pathogens like Toxoplasma. Do not sample meat until it is cooked. USDA recommends the following for meat preparation:
      • For WholeCuts of Meat (excluding poultry)
        Cook to at least 145° F (63° C) as measured with a food thermometer placed in the thickest part of the meat, then allow the meat to rest* for three minutes before carving or consuming. *According to USDA, &ldquoA &lsquorest time&rsquo is the amount of time the product remains at the final temperature, after it has been removed from a grill, oven, or other heat source. During the three minutes after meat is removed from the heat source, its temperature remains constant or continues to rise, which destroys pathogens.&rdquo
      • For Ground Meat (excluding poultry)
        Cook to at least 160° F (71° C) ground meats do not require a rest time.
      • For All Poultry (whole cuts and ground)
        Cook to at least 165° F (74° C) . The internal temperature should be checked in the innermost part of the thigh, innermost part of the wing, and the thickest part of the breast. Poultry do not require a rest time.
      • Freeze meat* for several days at sub-zero (0° F) temperatures before cooking to greatly reduce chance of infection. *Freezing does not reliably kill other parasites that may be found in meat (like certain species of Trichinella) or harmful bacteria. Cooking meat to USDA recommended internal temperatures is the safest method to destroy all parasites and other pathogens.
      • Peel or wash fruits and vegetables thoroughly before eating.
      • Do not eat raw or undercooked oysters, mussels, or clams (these may be contaminated with Toxoplasma that has washed into seawater).
      • Do not drink unpasteurized goat&rsquos milk.
      • Wash cutting boards, dishes, counters, utensils, and hands with soapy water after contact with raw meat, poultry, seafood, or unwashed fruits or vegetables.
      • Wear gloves when gardening and during any contact with soil or sand because it might be contaminated with cat feces that contain Toxoplasma. Wash hands with soap and water after gardening or contact with soil or sand.
      • Ensure that the cat litter box is changed daily. The Toxoplasma parasite does not become infectious until 1 to 5 days after it is shed in a cat&rsquos feces.
      • Wash hands with soap and water after cleaning out a cat&rsquos litter box.
      • Teach children the importance of washing hands to prevent infection.

      If you have a weakened immune system, please see guidelines for Immunocompromised Persons. For further information on safe food handling to help reduce foodborne illness visit the Fight BAC! ® website External external icon .

      If I am at risk, can I keep my cat?

      Yes, you may keep your cat if you are a person at risk for a severe infection (e.g., you have a weakened immune system or are pregnant) however, there are several safety precautions you should take to avoid being exposed to Toxoplasma gondii, including the following:

      • Ensure the cat litter box is changed daily. The Toxoplasma parasite does not become infectious until 1 to 5 days after it is shed in a cat&rsquos feces.
      • If you are pregnant or immunocompromised:
        • Avoid changing cat litter if possible. If no one else can perform the task, wear disposable gloves and wash your hands with soap and water afterwards.
        • Keep cats indoors. This is because cats become infected with Toxoplasma through hunting and eating rodents, birds, or other small animals that are infected with the parasite.
        • Do not adopt or handle stray cats, especially kittens. Do not get a new cat while you are pregnant or immunocompromised.
        • Feed cats only canned or dried commercial food or well-cooked table food, not raw or undercooked meats.
        • Keep your outdoor sandboxes covered.

        Your veterinarian can answer any other questions you may have regarding your cat and risk for toxoplasmosis.

        Once infected with Toxoplasma is my cat always able to spread the infection to me?

        No, cats only spread Toxoplasma in their feces for 1-3 weeks following infection with the parasite. Like humans, cats rarely have symptoms when infected, so most people do not know if their cat has been infected. Your veterinarian can answer any other questions you may have regarding your cat and risk for toxoplasmosis.


        Nepetalactol is a potent stimulant for silver vine response

        Previous attempts to isolate bioactive compounds from dried leaves of silver vine used steam distillation, alkaline heat treatment, and acid treatment (1315), all of which have the potential to decompose bioactive components. To avoid this problem, an organic solvent extract from silver vine leaves was resolved into six fractions using silica gel normal-phase column chromatography (Fig. 1A, step 1). The bioactivity of each of these fractions, corresponding to 1.2 g of leaves, was tested using four cats that responded positively to the unfractionated leaf extract (Fig. 1B). Only fraction 3 eluted by n-hexane/ethyl acetate (80:20, v:v) and fraction 4 eluted by n-hexane/ethyl acetate (70:30) induced face rubbing and rolling over in four and three subject cats, respectively. Although fraction 3 stimulated a more prolonged response than fraction 4 in all subjects (Fig. 1C), gas chromatography/mass spectrometry (GC/MS) analysis revealed that compounds with known bioactivity (isoiridomyrmecin, dihydronepetalactone, and isodihydronepetalactone) were at markedly lower levels in fraction 3 compared to fraction 4 (Fig. 1D). This suggests an important contribution of one or more unidentified compounds in fraction 3, which induce the behavioral response. To identify these unknown compounds, bioactive components in fraction 3 were further purified by normal-phase and reversed-phase high-performance liquid chromatography (HPLC) and finally enriched into a bimodal peak by HPLC (Fig. 1A, steps 2 to 5, and movie S1).

        (A) Five purification steps using column chromatography isolated bioactive compounds from silver vine leaves (bioactive fractions in red). A.U., arbitrary units. (B) An image of behavioral assay using cats to find bioactive fractions in purification steps (see movie S1). (C) Duration of face rubbing and rolling over toward fractions 3 and 4 in four cats. (D) Chemical structures and GC/MS mass chromatograms of isodihydronepetalactone, isoiridomyrmecin, and dihydronepetalactone in fraction 3 (green lines) and fraction 4 (gray lines) from step 1. Vertical line, retention time. (E) GC/MS total ion chromatogram of the final bioactive fraction (3-3-2-3) (iridodial, 1 and 2 cis-trans nepetalactol, 3 asterisks, unknown peaks). (F) Chemical structures of iridodial, cis-trans nepetalactol, and cis-trans nepetalactone. Photo credit: (B) Reiko Uenoyama, Iwate University.

        GC/MS of the final bioactive fraction (fraction 3-3-2-3) detected five major peaks (Fig. 1E) one, at 43.7 min, had a unique mass spectrum that matched (87%) a standard spectrum of nepetalactol (fig. S1A) in the Wiley MS library. Nepetalactol (Fig. 1F) is a common important biosynthetic precursor of iridoid monoterpenes (19) and shares a very similar structure with cis-trans nepetalactone (Fig. 1F) except for lactol and lactone moieties. A recent study also identified nepetalactol from silver vine leaves but did not examine its bioactivity in cats (20). We therefore synthesized cis-trans nepetalactol for further investigation. The mass spectrum of the 43.7-min peak had 98% similarity with authentic nepetalactol. Further, fraction 3-3-2-3 spiked with authentic nepetalactol yielded a single coeluting GC/MS peak with the same retention index (RI = 2078) as authentic nepetalactol alone (RI = 2080 fig. S1B). These results provide clear evidence that the peak at 43.7 min was cis-trans nepetalactol. We conjectured that the other two peaks (at 39.5 and 39.7 min) were stereoisomers of iridodial (Fig. 1F) the mass spectra (fig. S1C) were in good agreement with published spectra (21, 22). As iridodial has a readily epimerizing dialdehyde structure and is easily oxidized under atmospheric conditions (23), we thought that iridodial is an unsuitable stimulant for a reliable behavioral assay. Thus, further behavioral assays evaluated the bioactivity of chemically synthesized nepetalactol.

        Bioactivity of nepetalactol in felid and nonfelid species

        In this study, we used 25 laboratory cats that consisted of 18 positive and 7 negative responders to silver vine leaf extract (table S1). In behavioral assays using 15 of the 18 positive responder cats, all subjects exhibited face rubbing and rolling over in response to 50 μg of nepetalactol-impregnated filter paper (nepetalactol-paper) most of them then lost interest in the paper within 10 min after presentation (Fig. 2, A and B, and movie S2), very similar to the behavioral response toward unextracted plant materials (6). No cats exhibited a flehmen-like response, which is a functional behavior that transfers compounds such as pheromones from the oral cavity to the sensory vomeronasal organs (24). The duration of the behavioral response to nepetalactol-paper was more prolonged than that to control solvent filter paper (control-paper) presented simultaneously on the floor (Wilcoxon matched-pair test, one-tailed P = 0.0003 Fig. 2C). To test the generality of the bioactivity of nepetalactol, we also tested this similarly in 30 free-ranging feral cats using nepetalactol-paper versus control-paper. Seventeen of the 30 cats (57%) rubbed their faces against at least one paper. Almost all face rubbing and rolling among these 17 feral cats was directed toward the nepetalactol-paper such that the overall response toward nepetalactol-paper was substantially more prolonged than toward control-paper (P = 0.0001 Fig. 2, D and E, and movie S2), similar to laboratory cats. The other 13 cats did not respond to either papers, suggesting that they either were inherent negative responders (5) or just were not responsive in an unfamiliar test situation.

        (A) Images of behavioral assay of laboratory cats using nepetalactol-paper (pink arrow) and control-paper (gray arrow), fixed to the cage floor. Nepetalactol induced face rubbing and rolling over. (B) Activity patterns of face rubbing and rolling over toward nepetalactol-paper (pink) or control-paper (black) in 15 laboratory cats. Green arrows indicate end time points of observations. (C) Duration of face rubbing and rolling over toward nepetalactol-paper (pink) and control-paper (gray) in 15 laboratory cats. (D) Images of free-ranging feral cats exhibiting face rubbing and rolling over toward nepetalactol-paper. (E) Duration of face rubbing and rolling over toward nepetalactol-paper (pink) and control-paper (gray) in the 17 of 30 feral cats that showed a response to test papers. (F) Duration of face rubbing and rolling over toward nepetalactone (green), nepetalactol (pink), and four reported active compounds (pale pink) in 12 laboratory cats. (G) An Amur leopard (left) and a jaguar (right) exhibiting the typical response toward nepetalactol-paper. (H) Duration of face rubbing and rolling over toward nepetalactol-paper (pink) and control-paper (gray) in five nondomesticated felids. (C, E, F, and H) Boxes show median and interquartile range, whiskers are minimum and maximum, and points are individual values (black, domestic cats green, Amur leopard red, jaguars blue, Eurasian lynx). P values from one-tailed Wilcoxon matched-pair tests (C, E, and H) and Bonferroni-Dunn post-hoc test (F). See movie S2 for (A) and (D) and movie S3 for (G). Photo credit: (A, D, and G) Reiko Uenoyama, Iwate University.

        Next, we compared the behavioral responses of 12 of the 18 positive responder cats to each of the known bioactive iridoids. Nepetalactol (silver vine) and nepetalactone (catnip) induced more prolonged face rubbing and rolling than other iridoids (Fig. 2F χ 2 = 24.0, df = 5, P = 0.0002). At least one cat did not exhibit the characteristic response toward each iridoid except for nepetalactol. Further, the nepetalactol content of silver vine leaves (20.71 μg/g of wet weight) was much higher than isoiridomyrmecin (1.42 μg/g), iridomyrmecin (below the GC/MS detection limit), dihydronepetalactone (<0.18 μg/g), or isodihydronepetalactone content (<0.18 μg/g). Considering also that fraction 3 had stronger bioactivity than fraction 4, as shown in Fig. 1C, and nepetalactol had bioactivity in all of the 18 positive responder cats tested (Fig. 2, C and F), nepetalactol is the most potent and major bioactive iridoid in silver vine leaves. We concluded that nepetalactol is the most suitable stimulant for a reliable and reproducible behavioral assay.

        Nondomesticated captive felids tested at zoos in Japan (an Amur leopard, P. pardus orientalis two jaguars, P. onca two Eurasian lynx, L. lynx) also exhibited more prolonged face rubbing and rolling on nepetalactol-paper than on control-paper (exact P = 0.031 Fig. 2, G and H, and movie S3), a bias that did not differ significantly from the laboratory cats (Mann-Whitney U test of bias z = 1.27, P = 0.23).

        We also tested the response of domestic dogs (Canis lupus familiaris, n = 8) and laboratory mice (C57BL/6 or BALB/cAJcl strain males, n = 10) to nepetalactol. All animals tested were uninterested in nepetalactol, and none exhibited a silver vine response (movie S3). The lack of response to nepetalactol in dogs and mice differed substantially from the positive response found among 72% of the 25 laboratory cats tested in this study (Fisher’s exact tests, domestic dogs: P < 0.0005 mice: P < 0.0005).

        Activation of the μ-opioid system during silver vine response in cats

        Subjective observations of the behavioral response of cats to catnip suggest that they may experience a positive reaction that has often been interpreted as extreme pleasure (17, 25). Thus, we hypothesized that olfactory reception of nepetalactol stimulates the μ-opioid system, which controls rewarding and euphoric effects in humans (26). First, we examined temporal changes in plasma levels of β-endorphin (a peptide hormone and an endogenous opiate) in five cats 5 min before and after exposure to 200 μg of nepetalactol (corresponding to the contents in approximately 10 leaves) on day 1 (inducing the behavioral response) and then to a blank stimulus control 4 days later (Fig. 3A). Plasma β-endorphin concentration was markedly elevated after exposure to nepetalactol but not after exposure to a control stimulus [repeated-measures analysis of variance (ANOVA), interaction between stimulus and time point: F1,4 = 9.97, P = 0.034 Fig. 3B].

        (A) Design to assess temporal changes in plasma β-endorphin levels after presentation of nepetalactol-paper (day 1) and control-paper (day 5). (B) Plasma β-endorphin concentration before (Pre) and after (Post) nepetalactol stimulus (pink) and control stimulus (gray) (mean ± SEM, n = 5). P values from repeated-measures ANOVAs (data log-transformed to meet parametric assumptions) after finding a significant interaction between stimulus and time point (P = 0.034). (C) Design to assess behavioral response to nepetalactol following saline (day 1) and then naloxone (μ-opioid antagonist) or saline administration (day 2). IM, intramuscular injection. (D and E) Duration of face rubbing and rolling over toward nepetalactol on day 1 (saline administration) and day 2 (D, naloxone administration E, saline administration) (Wilcoxon matched-pair test, two-tailed n = 6). See movie S4 for (D). Box and whisker plots show median, interquartile range, minimum, maximum, and individual values. (B, D, and E) Points connected by lines indicate same individuals.

        To test whether the μ-opioid system is directly involved in regulation of the behavioral response to nepetalactol, we examined the behavioral response to nepetalactol in six cats that had been administered saline (day 1) or naloxone (day 2), an antagonist of μ-opioid receptors (Fig. 3C). While all cats exhibited a typical response to nepetalactol-paper after saline administration, the duration of their characteristic rubbing and rolling response was reduced significantly after naloxone administration on the following day (Wilcoxon matched-pair test, two-tailed exact P = 0.031 Fig. 3D and movie S4). By contrast, six cats administered saline on both days as a control showed no reduction in response to nepetalactol (P = 1.00 Fig. 3E), differing significantly from the reduced response caused by naloxone (Mann-Whitney test of change between day 1 and day 2 P = 0.04). Naloxone did not affect the duration of other activities compared to vehicle alone (walking: P = 0.31 grooming: P = 0.31 fig. S2, A and B), confirming that the naloxone dose administered did not disturb locomotor activities or motor functions during the observations. Inhibition of the μ-opioid system specifically suppressed the rubbing and rolling response in the cats. These results demonstrate that the μ-opioid system is involved in the induction of the feline behavioral response.

        Mosquito-repellent activity of nepetalactol

        The consistent expression of such a characteristic response to nepetalactol suggests that the response has an important adaptive function for cats. On the basis of reports that nepetalactone from catnip has mosquito-repellent activity when applied to humans (2729), we hypothesized that the characteristic rubbing and rolling against plants allows cats to transfer nepetalactol or nepetalactone onto the fur for chemical defense against mosquitoes and possibly also against other biting arthropods. In this study, we tested whether nepetalactol is repellent to Aedes albopictus, a mosquito common in Japan and China (30). A. albopictus avoided both silver vine leaves (five leaves, containing approximately 100 μg of nepetalactol) and nepetalactol alone (50 μg, 200 μg, and 2 mg) compared to a solvent control, when each was placed separately into test cages that had shelters into which A. albopictus could move (Fig. 4A ANOVA, effect of stimulus F4,15 = 79.93, P < 0.0001 planned contrasts confirmed that avoidance of each test stimulus was significantly greater than the control, P < 0.003 Fig. 4B). This indicates that nepetalactol acts as a repellent against A. albopictus, consistent with the previously reported repellent activity of nepetalactone (29).

        (A) A test cage to assess mosquito repellency. Fourteen to 22 mosquitoes were placed into an acrylic cage that had a plastic bag as a shelter into which the mosquitoes could move. A dish containing the test stimulus (arrow) was placed on the floor of the cage. (B) Mosquito (A. albopictus) repellency (mean ± SEM %) of nepetalactol (2 mg, 200 μg, and 50 μg), five fresh silver vine leaves, or solvent control (n = 4). P values from ANOVA planned contrasts to the control stimulus. Photo credit: (A) Reiko Uenoyama, Iwate University.

        The function of rubbing behavior in nepetalactol-stimulated cats

        Next, we examined whether the characteristic rubbing and rolling response functions to transfer nepetalactol to the cat’s face, head, and body. To establish the importance of contact with the source (to rub nepetalactol onto the fur), seven laboratory cats were tested with 200 μg of nepetalactol versus control on papers placed on the test cage walls or ceiling. In this arrangement, cats could rub the papers with their faces, but rolling would not allow rubbing contact with the stimulus. As expected, all subjects rubbed their faces and heads on nepetalactol-paper placed on the cage walls more frequently than on control-paper (Wilcoxon matched-pair test, exact P = 0.008 Fig. 5A and movie S5). When papers were more difficult to contact on the cage ceiling, five of seven subject cats stood on their hind legs, held on to the ceiling mesh with their fore paws, and rubbed their faces and heads on nepetalactol-paper more frequently than on control-paper (exact P = 0.031 Fig. 5B and movie S5). However, no subject cat rolled on the ground when test papers were on the cage walls or ceiling, in stark contrast to typical rolling observed in all subjects when filter papers were placed on the floor (χ 2 = 29.0, df = 1, P < 0.0001). Strong motivation to contact nepetalactol was further evidenced in high-ceiling cages, when two of seven subjects climbed the 116-cm walls to reach nepetalactol-paper on the ceiling and then proceeded to rub their faces and heads on nepetalactol-paper as before (Fig. 5C and movie S6). Thus, rubbing is specifically targeted at the nepetalactol source.

        (A to C) Cats face-rubbed in bioassays with nepetalactol-papers (pink) and control-papers (gray) on the cage wall (A), low ceiling (B), or high ceiling (C). See movie S5 for (A) and (B) and movie S6 for (C). (A and B) Frequency of face rubs toward nepetalactol-paper (pink) and control-paper (gray) (n = 7). (D and E) To assess whether nepetalactol was transferred to cat’s face and head fur by the characteristic response, subject cats (n = 5) were tested with wipes from cats that had rubbed nepetalactol-paper with (donor N+) or without (donor N−) physical contact versus wipes from unstimulated cats (donor U). Box and whisker plots show median, interquartile range, minimum, maximum, and individual values. (F to H) Numbers of A. albopictus landing on treated versus untreated cats (n = 6 pairs, anesthetized for 10-min test), when one cat was treated with nepetalactol (F), had rubbed on silver vine leaves (Leaves +, G), and had not rubbed on the leaves (Leaves −, H). P values from nonparametric Wilcoxon matched-pair tests (one-tailed, A and B), linear mixed effects model (E), or repeated-measures ANOVA (F to H). Photo credit (A to D): Reiko Uenoyama, Iwate University.

        Rubbing against the source (200 μg of nepetalactol) should transfer the material to the fur, but the quantity of nepetalactol in ethanol-soaked cotton used for wiping the face and head fur was below the limit of detection (2.2 μg) by our experimental procedure using GC/MS as a detector, indicating that no more than 1% of the material was recovered on the cotton wipe. To provide a more sensitive test, subject cats were tested with face and head wipes from donors that had rubbed nepetalactol-papers with or without direct physical contact versus wipes from unstimulated donors (Fig. 5D). We predicted that subjects would detect nepetalactol on papers used to wipe donors that had contact-rubbed nepetalactol-paper, but they would not respond to wipes from unstimulated donors or from donors that rubbed in response to nepetalactol when they could not physically contact the source. In agreement with our prediction, subjects rubbed and rolled only in response to wipes from donors that had physically contact-rubbed nepetalactol-papers (Fig. 5E interaction between donor nepetalactol stimulation and direct contact, F1,4 = 9.97, P = 0.034 behavioral response to donor with nepetalactol physical contact, F1,4 = 12.35, P = 0.025 behavioral response to donor without nepetalactol physical contact, F1,4 = 0.32, P = 0.60). Thus, face rubbing transfers nepetalactol onto the cat’s fur.

        Silver vine response provides cats with mosquito repellency

        To examine whether nepetalactol on the fur protects cats from mosquito bites, the heads of six pairs of anesthetized cats were placed into opposite sides of a test cage. One cat’s head had been treated with nepetalactol (500 μg) and the other with the appropriate solvent control. The number of A. albopictus landing on the nepetalactol-treated head was half the number landing on the control head on average (repeated-measures ANOVA, F1,5 = 8.56, P = 0.033 Fig. 5F), showing significant repellence. Lastly, to investigate a more natural situation, we assessed whether cats responding to silver vine leaves transfer sufficient active compound(s) to repel A. albopictus, compared to unstimulated cat controls in the same two-head test. Cats that had rubbed against silver vine leaves were significantly avoided by A. albopictus compared to control cats that had not been stimulated by the leaves (repeated-measures ANOVA, F1,5 = 11.78, P = 0.019 Fig. 5G). By contrast, there was no significant difference in the number of A. albopictus landing on the head of control cats versus cats that had not rubbed when presented with silver vine leaves (F1,5 = 0.029, P = 0.87 Fig. 5H difference in bias between tests, F1,10 = 9.21, P = 0.013). These results show that nepetalactol, transferred to face and head fur by rubbing against silver vine leaves, functions as a repellent against A. albopictus in cats. This is convincing evidence that the characteristic rubbing and rolling response functions to transfer plant chemicals that provide mosquito repellency to cats.

        Supplementary Material

        Acton, A. E., Munson, L., and Waddell, W. T. (2000). Survey of necropsy results In captive red wolves (Canis Rufus), 1992-1996. J. Zoo Wildl. Med. 31, 2𠄸. doi: 10.1638/1042-7260(2000)031[0002:sonric]2.0.co2

        Alessandri, G., Milani, C., Mancabelli, L., Mangifesta, M., Lugli, G. A., Viappiani, A., et al. (2019a). Metagenomic dissection of the canine gut microbiota: insights into taxonomic, metabolic and nutritional features. Environ. Microbiol. 21, 1331�. doi: 10.1111/1462-2920.14540

        Alessandri, G., Milani, C., Mancabelli, L., Mangifesta, M., Lugli, G. A., Viappiani, A., et al. (2019b). The impact of human-facilitated selection on the gut microbiota of domesticated mammals. FEMS Microbiol. Ecol. 95:fiz121. doi: 10.1093/femsec/fiz121

        Allen-Vercoe, E., Strauss, J., and Chadee, K. (2011). Fusobacterium nucleatum: An emerging gut pathogen? Gut Microbes 2, 294�. doi: 10.4161/gmic.2.5.18603

        Amato, K. R., Metcalf, J. L., Song, S. J., Hale, V. L., Clayton, J., Ackermann, G., et al. (2016). Using the gut microbiota as a novel tool for examining colobine primate GI health. Glob. Ecol. Conserv. 7, 225�. doi: 10.1016/j.gecco.2016.06.004

        Anderson, M. J. (2017). “Permutational Multivariate Analysis of Variance (PERMANOVA),” in Wiley StatsRef: Statistics Reference Online, ed. W. StatsRef (Hoboken, NY: John Wiley & Sons), 1�. doi: 10.1002/9781118445112.stat07841

        Association of Zoos and Aquariums Canid Taxonomic Advisory Group. (2012). Large Canid (Canidae) Care Manual. Silver Spring, MD: Association of Zoos and Aquariums.

        Axelsson, E., Ratnakumar, A., Arendt, M.-L., Maqbool, K., Webster, M. T., Perloski, M., et al. (2013). The genomic signature of dog domestication reveals adaptation to a starch-rich diet. Nature 495, 360�. doi: 10.1038/nature11837

        Aziz, Q., Doré, J., Emmanuel, A., Guarner, F., and Quigley, E. M. M. (2013). Gut microbiota and gastrointestinal health: current concepts and future directions. Neurogastroenterol. Motil. 25, 4�. doi: 10.1111/nmo.12046

        Bamberger, C., Rossmeier, A., Lechner, K., Wu, L., Waldmann, E., Fischer, S., et al. (2018). A walnut-enriched diet affects gut microbiome in healthy caucasian subjects: a randomized, controlled trial. Nutrients 10:244. doi: 10.3390/nu10020244

        Bermingham, E. N., Maclean, P., Thomas, D. G., Cave, N. J., and Young, W. (2017). Key bacterial families (Clostridiaceae, Erysipelotrichaceae and Bacteroidaceae) are related to the digestion of protein and energy in dogs. PeerJ 5:e3019. doi: 10.7717/peerj.3019

        Bolyen, E., Rideout, J. R., Dillon, M. R., Bokulich, N. A., Abnet, C., Al-Ghalith, G. A., et al. (2018). QIIME 2: reproducible, interactive, scalable, and extensible microbiome data science. PeerJ Inc 6:e27295v2. doi: 10.7287/peerj.preprints.27295v2

        Butowski, C. F., Thomas, D. G., Young, W., Cave, N. J., McKenzie, C. M., Rosendale, D. I., et al. (2019). Addition of plant dietary fibre to a raw red meat high protein, high fat diet, alters the faecal bacteriome and organic acid profiles of the domestic cat (Felis catus). PLoS One 14:e0216072. doi: 10.1371/journal.pone.0216072

        Callahan, B. J., McMurdie, P. J., Rosen, M. J., Han, A. W., Johnson, A. J. A., and Holmes, S. P. (2016). DADA2: high-resolution sample inference from Illumina amplicon data. Nat. Methods 13, 581�. doi: 10.1038/nmeth.3869

        Chambers, E. S., Preston, T., Frost, G., and Morrison, D. J. (2018). Role of gut microbiota-generated short-chain fatty acids in metabolic and cardiovascular health. Curr. Nutr. Rep. 7, 198�. doi: 10.1007/s13668-018-0248-8

        Cook, D. P., Gysemans, C., and Mathieu, C. (2018). Lactococcus lactis as a versatile vehicle for tolerogenic immunotherapy. Front. Immunol. 8:1961. doi: 10.3389/fimmu.2017.01961

        Core Team, R. (2018). R: A language and environment for statistical computing. Vienna: R Foundation for Statistical Computing.

        Corthay, A. (2009). How do regulatory T cells work? Scand. J. Immunol. 70, 326�. doi: 10.1111/j.1365-3083.2009.02308.x

        Craven, L. J., Silverman, M., and Burton, J. P. (2017). Transfer of altered behaviour and irritable bowel syndrome with diarrhea (IBS-D) through fecal microbiota transplant in mouse model indicates need for stricter donor screening criteria. Ann. Transl. Med. 5:490. doi: 10.21037/atm.2017.10.03

        Dandrieux, J. R. S. (2016). Inflammatory bowel disease versus chronic enteropathy in dogs: are they one and the same? J. Small. Anim. Pract. 57, 589�. doi: 10.1111/jsap.12588

        Davis, N. M., Proctor, D., Holmes, S. P., Relman, D. A., and Callahan, B. J. (2017). Simple statistical identification and removal of contaminant sequences in marker-gene and metagenomics data. Microbiome 6:226.

        De Caceres, M., and Legendre, P. (2009). Associations between species and groups of sites: indices and statistical inference. Ecology 90, 3566�. doi: 10.1890/08-1823.1

        De Cres, M., Legendre, P., Wiser, S. K., and Brotons, L. (2012). Using species combinations in indicator value analyses. Methods Ecol. Evol. 3, 973�. doi: 10.1111/j.2041-210X.2012.00246.x

        De Maesschalck, C., Van Immerseel, F., Eeckhaut, V., De Baere, S., Cnockaert, M., Croubels, S., et al. (2014). Faecalicoccus acidiformans gen. nov., sp. nov., isolated from the chicken caecum, and reclassification of Streptococcus pleomorphus (Barnes et al. 1977), Eubacterium biforme (Eggerth 1935) and Eubacterium cylindroides (Cato et al. 1974) as Faecalicoccus pleomorphus comb. nov., Holdemanella biformis gen. nov., comb. nov. and Faecalitalea cylindroides gen. nov., comb. nov., respectively, within the family Erysipelotrichaceae. Int. J. Syst. Evol. Microbiol. 64, 3877�. doi: 10.1099/ijs.0.064626-0

        Dellinger, J. A., Ortman, B. L., Steury, T. D., Bohling, J., and Waits, L. P. (2011). Food Habits of Red Wolves during Pup-Rearing Season. Southeast. Nat. 10, 731�. doi: 10.1656/058.010.0412

        den Besten, G., Bleeker, A., Gerding, A., van Eunen, K., Havinga, R., van Dijk, T. H., et al. (2015). Short-Chain fatty acids protect against high-fat diet-induced obesity via a PPARγ-Dependent Switch From Lipogenesis to Fat Oxidation. Diabetes 64, 2398�. doi: 10.2337/db14-1213

        den Besten, G., van Eunen, K., Groen, A. K., Venema, K., Reijngoud, D.-J., and Bakker, B. M. (2013). The role of short-chain fatty acids in the interplay between diet, gut microbiota, and host energy metabolism. J. Lipid Res. 54, 2325�. doi: 10.1194/jlr.R036012

        Deng, P., and Swanson, K. S. (2015). Gut microbiota of humans, dogs and cats: current knowledge and future opportunities and challenges. Br. J. Nutr. 113, S6–S17. doi: 10.1017/S0007114514002943

        Dhanasiri, A. K. S., Brunvold, L., Brinchmann, M. F., Korsnes, K., Bergh, Ø, and Kiron, V. (2011). Changes in the intestinal microbiota of wild atlantic cod (Gadus morhua) L. upon captive rearing. Microb. Ecol. 61, 20�. doi: 10.1007/s00248-010-9673-y

        Dubé, M. P., Park, S. Y., Ross, H., Love, T. M. T., Morris, S. R., and Lee, H. Y. (2018). Daily HIV pre-exposure prophylaxis (PrEP) with tenofovir disoproxil fumarate-emtricitabine reduced Streptococcus and increased Erysipelotrichaceae in rectal microbiota. Sci. Rep. 8:15212. doi: 10.1038/s41598-018-33524-6

        Falony, G., Vandeputte, D., Caenepeel, C., Vieira-Silva, S., Daryoush, T., Vermeire, S., et al. (2019). The human microbiome in health and disease: hype or hope. Acta. Clin. Belg. 74, 53�. doi: 10.1080/17843286.2019.1583782

        Finlayson-Trick, E. C. L., Getz, L. J., Slaine, P. D., Thornbury, M., Lamoureux, E., Cook, J., et al. (2017). Taxonomic differences of gut microbiomes drive cellulolytic enzymatic potential within hind-gut fermenting mammals. PLoS One 12:e0189404. doi: 10.1371/journal.pone.0189404

        Fortes, C. M. L. S., Carciofi, A. C., Sakomura, N. K., Kawauchi, I. M., and Vasconcellos, R. S. (2010). Digestibility and metabolizable energy of some carbohydrate sources for dogs. Anim. Feed Sci. Tech. 156, 121�. doi: 10.1016/j.anifeedsci.2010.01.009

        Fox, J., and Weisberg, S. (2011). An Companion to Applied Regression, Second Edition. Thousand Oaks, CA: Sage.

        Gerritsen, J. (2015). The genus Romboutsia: Genomic And Functional Characterization of Novel Bacteria Dedicated to Life in The Intestinal Tract. Wageningen: Wageningen University.

        Gerritsen, J., Hornung, B., Ritari, J., Paulin, L., Rijkers, G. T., Schaap, P. J., et al. (2019). A comparative and functional genomics analysis of the genus Romboutsia provides insight into adaptation to an intestinal lifestyle. bioRxiv [Preprint] doi: 10.1101/845511

        Gómez-Gallego, C., Junnila, J., Männikkö, S., Hämeenoja, P., Valtonen, E., Salminen, S., et al. (2016). A canine-specific probiotic product in treating acute or intermittent diarrhea in dogs: a double-blind placebo-controlled efficacy study. Vet. Microbiol. 197, 122�. doi: 10.1016/j.vetmic.2016.11.015

        Gon๺lves, P., Araújo, J. R., and Di Santo, P. J. (2018). A cross-talk between microbiota-derived short-chain fatty acids and the host mucosal immune system regulates intestinal homeostasis and inflammatory bowel disease. Inflamm. Bowel Dis. 24, 558�. doi: 10.1093/ibd/izx029

        Handl, S., Dowd, S. E., Garcia-Mazcorro, J. F., Steiner, J. M., and Suchodolski, J. S. (2011). Massive parallel 16S rRNA gene pyrosequencing reveals highly diverse fecal bacterial and fungal communities in healthy dogs and cats. FEMS Microbiol. Ecol. 76, 301�. doi: 10.1111/j.1574-6941.2011.01058.x

        Hang, I., Rinttila, T., Zentek, J., Kettunen, A., Alaja, S., Apajalahti, J., et al. (2012). Effect of high contents of dietary animal-derived protein or carbohydrates on canine faecal microbiota. BMC Vet. Res. 8:90. doi: 10.1186/1746-6148-8-90

        Hedrick, P. W., and Fredrickson, R. J. (2008). Captive breeding and the reintroduction of Mexican and red wolves. Mol. Ecol. 17, 344�. doi: 10.1111/j.1365-294X.2007.03400.x

        Henson, L. H., Songsasen, N., Waddell, W., Wolf, K. N., Emmons, L., Gonzalez, S., et al. (2017). Characterization of genetic variation and basis of inflammatory bowel disease in the Toll-like receptor 5 gene of the red wolf and the maned wolf. Endanger. Species Res. 32, 135�. doi: 10.3354/esr00790

        Hinton, J. W., Chamberlain, M. J., and Rabon, D. R. (2013). Red wolf (Canis rufus) recovery: a review with suggestions for future research. Animals 3, 722�. doi: 10.3390/ani3030722

        Jandhyala, S. M., Talukdar, R., Subramanyam, C., Vuyyuru, H., Sasikala, M., and Reddy, D. N. (2015). Role of the normal gut microbiota. World. J. Gastroenterol. 21, 8787�. doi: 10.3748/wjg.v21.i29.8787

        Jergens, A. E., Schreiner, C. A., Frank, D. E., Niyo, Y., Ahrens, F. E., Eckersall, P. D., et al. (2003). A scoring index for disease activity in canine inflammatory bowel disease. J. Vet. Intern. Med. 17, 291�. doi: 10.1111/j.1939-1676.2003.tb02450.x

        Karu, N., Deng, L., Slae, M., Guo, A. C., Sajed, T., Huynh, H., et al. (2018). A review on human fecal metabolomics: methods, applications and the human fecal metabolome database. Anal. Chim. Acta 1030, 1�. doi: 10.1016/j.aca.2018.05.031

        Kim, J., An, J.-U., Kim, W., Lee, S., and Cho, S. (2017). Differences in the gut microbiota of dogs (Canis lupus familiaris) fed a natural diet or a commercial feed revealed by the Illumina MiSeq platform. Gut Pathogens 9:68. doi: 10.1186/s13099-017-0218-5

        Marchesi, J. R., Adams, D. H., Fava, F., Hermes, G. D. A., Hirschfield, G. M., Hold, G., et al. (2016). The gut microbiota and host health: a new clinical frontier. Gut 65, 330�. doi: 10.1136/gutjnl-2015-309990

        McKenzie, V. J., Song, S. J., Delsuc, F., Prest, T. L., Oliverio, A. M., Korpita, T. M., et al. (2017). The effects of captivity on the mammalian gut microbiome. Integr. Comp. Biol. 57, 690�. doi: 10.1093/icb/icx090

        McVey, J. M., Cobb, D. T., Powell, R. A., Stoskopf, M. K., Bohling, J. H., Waits, L. P., et al. (2013). Diets of sympatric red wolves and coyotes in northeastern North Carolina. J. Mammal 94, 1141�. doi: 10.1644/13-MAMM-A-109.1

        Minamoto, Y., Otoni, C. C., Steelman, S. M., Büyükleblebici, O., Steiner, J. M., Jergens, A. E., et al. (2015). Alteration of the fecal microbiota and serum metabolite profiles in dogs with idiopathic inflammatory bowel disease. Gut Microbes 6, 33�. doi: 10.1080/19490976.2014.997612

        Miyake, S., Kim, S., Suda, W., Oshima, K., Nakamura, M., Matsuoka, T., et al. (2015). Dysbiosis in the gut microbiota of patients with multiple sclerosis, with a striking depletion of species belonging to clostridia XIVa and IV clusters. PLoS One 10:e0137429. doi: 10.1371/journal.pone.0137429

        Muletz-Wolz, C. R., Fleischer, R. C., and Lips, K. R. (2019a). Fungal disease and temperature alter skin microbiome structure in an experimental salamander system. Mol. Ecol. 28, 2917�. doi: 10.1111/mec.15122

        Muletz-Wolz, C. R., Kurata, N. P., Himschoot, E. A., Wenker, E. S., Quinn, E. A., Hinde, K., et al. (2019b). Diversity and temporal dynamics of primate milk microbiomes. Am. J. Primatol. 81:e22994. doi: 10.1002/ajp.22994

        Müller, M., Hermes, G. D. A., Canfora, E. E., Smidt, H., Masclee, A. A. M., Zoetendal, E. G., et al. (2020). Distal colonic transit is linked to gut microbiota diversity and microbial fermentation in humans with slow colonic transit. Am. J. of Physiol. Gastrointest. Liver Physiol. 318, G361–G369. doi: 10.1152/ajpgi.00283.2019

        Nelson, T. M., Rogers, T. L., Carlini, A. R., and Brown, M. V. (2013). Diet and phylogeny shape the gut microbiota of Antarctic seals: a comparison of wild and captive animals. Environ. Microbiol. 15, 1132�. doi: 10.1111/1462-2920.12022

        Nishida, A. H., and Ochman, H. (2018). Rates of gut microbiome divergence in mammals. Mol. Ecol. 27, 1884�. doi: 10.1111/mec.14473

        Ohira, H., Tsutsui, W., and Fujioka, Y. (2017). Are short chain fatty acids in gut microbiota defensive players for inflammation and atherosclerosis? J. Atheroscler. Thromb. 24, 660�. doi: 10.5551/jat.RV17006

        Oksanen, J., Guillaume Blanchet, F., Friendly, M., Kindt, R., Legendre, P., McGlinn, D., et al. (2019). Vegan: Community Ecology Package. R package version 2.5-5. Available online at: (accessed September 1,2019).

        Omori, M., Maeda, S., Igarashi, H., Ohno, K., Sakai, K., Yonezawa, T., et al. (2017). Fecal microbiome in dogs with inflammatory bowel disease and intestinal lymphoma. J. Vet. Med. Sci. 79, 1840�. doi: 10.1292/jvms.17-0045

        Parada Venegas, D., De la Fuente, M. K., Landskron, G., González, M. J., Quera, R., Dijkstra, G., et al. (2019). Short chain fatty acids (SCFAs)-mediated gut epithelial and immune regulation and its relevance for inflammatory bowel diseases. Front. Immunol 10:277. doi: 10.3389/fimmu.2019.00277

        Phillips, M. (2018). Canis rufus. The IUCN Red List of Threatened Species 2018: e.T3747A119741683. Available online at: (Accessed October, 2019)

        Phillips, M. K., Henry, V. G., and Kelly, B. T. (2003). Restoration of the red wolf in wolves: behavior, ecology and conservation. Chicago, IL: University of Chicago Press, 272�.

        Pilla, R., and Suchodolski, J. S. (2020). The role of the canine gut microbiome and metabolome in health and gastrointestinal disease. Front. Vet. Sci. 6:498. doi: 10.3389/fvets.2019.00498

        Poeker, S. A. T. M. (2019). Towards Understanding The Modulation Potential Of Dietary Fibers On Intestinal Microbiota Using Human And A Novel Murine Intestinal Fermentation Model. Zurich: ETH Zurich. Doctoral thesis.

        Price, M. N., Dehal, P. S., and Arkin, A. P. (2009). FastTree: computing large minimum evolution trees with profiles instead of a distance matrix. Mol. Biol. Evol. 26, 1641�. doi: 10.1093/molbev/msp077

        Ratajczak, W., Rył, A., Mizerski, A., Walczakiewicz, K., Sipak, O., and Laszczyńska, M. (2019). Immunomodulatory potential of gut microbiome-derived short-chain fatty acids (SCFAs). Acta Biochim. Pol. 66, 1�. doi: 10.18388/abp.2018_2648

        Ríos-Covián, D., Ruas-Madiedo, P., Margolles, A., Gueimonde, M., de los Reyes-Gavilán, C. G., and Salazar, N. (2016). Intestinal short chain fatty acids and their link with diet and human health. Front. Microbiol. 7:185. doi: 10.3389/fmicb.2016.00185

        Rist, V. T. S., Weiss, E., Eklund, M., and Mosenthin, R. (2013). Impact of dietary protein on microbiota composition and activity in the gastrointestinal tract of piglets in relation to gut health: a review. Animal 7, 1067�. doi: 10.1017/S1751731113000062

        Rohland, N., and Reich, D. (2012). Cost-effective, high-throughput DNA sequencing libraries for multiplexed target capture. Genome Res. 22, 939�. doi: 10.1101/gr.128124.111

        Russel, J., Thorsen, J., Brejnrod, A. D., Bisgaard, H., Sorensen, S., and Burmolle, M. (2018). DAtest: a framework for choosing differential abundance or expression method. bioRxiv[Preprint] doi: 10.1101/241802

        Seeley, K. E., Garner, M. M., Waddell, W. T., and Wolf, K. N. (2016). A survey of diseases in captive red wolves (Canis rufus), 1997�. J. Zoo Wildlife Med. 47, 83�. doi: 10.1638/2014-0198.1

        Songsasen, N., and Rodden, M. D. (2010). The role of the Species Survival Plan in maned wolf (Chrysocyon brachyurus) conservation. Int. Zoo Yb. 44, 136�. doi: 10.1111/j.1748-1090.2009.00093.x

        Su, T., Liu, R., Lee, A., Long, Y., Du, L., Lai, S., et al. (2018). Altered intestinal microbiota with increased abundance of Prevotella is associated with high risk of diarrhea-predominant irritable bowel syndrome. Gastroent. Res. Pract. 2018:6961783. doi: 10.1155/2018/6961783

        Suchodolski, J. S. (2011). Companion animal symposium: Microbes and gastrointestinal health of dogs and cats. J. Anim. Sci. 89, 1520�. doi: 10.2527/jas.2010-3377

        Suchodolski, J. S. (2016). Diagnosis and interpretation of intestinal dysbiosis in dogs and cats. Vet. J. 215, 30�. doi: 10.1016/j.tvjl.2016.04.011

        Suchodolski, J. S., Dowd, S. E., Wilke, V., Steiner, J. M., and Jergens, A. E. (2012a). 16S rRNA gene pyrosequencing reveals bacterial dysbiosis in the duodenum of dogs with idiopathic inflammatory bowel disease. PLoS One 7:e39333. doi: 10.1371/journal.pone.0039333

        Suchodolski, J. S., Markel, M. E., Garcia-Mazcorro, J. F., Unterer, S., Heilmann, R. M., Dowd, S. E., et al. (2012b). The fecal microbiome in dogs with acute diarrhea and idiopathic inflammatory bowel disease. PLoS One 7:e51907. doi: 10.1371/journal.pone.0051907

        Tedjo, D. I., Smolinska, A., Savelkoul, P. H., Masclee, A. A., van Schooten, F. J., Pierik, M. J., et al. (2016). The fecal microbiota as a biomarker for disease activity in Crohn’s disease. Sci. Rep. 6:35216. doi: 10.1038/srep35216

        Trinh, P., Zaneveld, J. R., Safranek, S., and Rabinowitz, P. M. (2018). One health relationships between human, animal, and environmental microbiomes: a mini-review. Front. Public Health 6:235. doi: 10.3389/fpubh.2018.00235

        US Fish and Wildlife Service (2016). History of the Red Wolf Recovery Program. Available online at: (accessed October 2019)

        van der Beek, C. M., Canfora, E. E., Lenaerts, K., Troost, F. J., Olde Damink, S. W. M., Holst, J. J., et al. (2016). Distal, not proximal, colonic acetate infusions promote fat oxidation and improve metabolic markers in overweight/obese men. Clin. Sci. (Lond). 130, 2073�. doi: 10.1042/CS20160263

        Vandeputte, D., Falony, G., Vieira-Silva, S., Tito, R. Y., Joossens, M., and Raes, J. (2016). Stool consistency is strongly associated with gut microbiota richness and composition, enterotypes and bacterial growth rates. Gut 65, 57�. doi: 10.1136/gutjnl-2015-309618

        Vital, M., Howe, A. C., and Tiedje, J. M. (2014). Revealing the bacterial butyrate synthesis pathways by analyzing (Meta)genomic Data. mBio 5:14. doi: 10.1128/mBio.00889-14

        Wang, Q., Garrity, G. M., Tiedje, J. M., and Cole, J. R. (2007). Naïve Bayesian classifier for rapid assignment of rRNA sequences into the new bacterial taxonomy. Appl. Environ. Microbiol. 73, 5261�. doi: 10.1128/AEM.00062-07

        Weiss, G. A., and Hennet, T. (2017). Mechanism and consequences of intestinal dysbiosis. Cell. Mol. Life Sci. 74, 2959�. doi: 10.1007/s00018-017-2509-x

        Weiss, S., Xu, Z. Z., Peddada, S., Amir, A., Bittinger, K., Gonzalez, A., et al. (2017). Normalization and microbial differential abundance strategies depend upon data characteristics. Microbiome 5:27. doi: 10.1186/s40168-017-0237-y

        Williams, C. L., Caraballo-Rodríguez, A. M., Allaband, C., Zarrinpar, A., Knight, R., and Gauglitz, J. M. (2019). Wildlife-microbiome interactions and disease: exploring opportunities for disease mitigation across ecological scales. Drug Discov. Today: Dis. Models 28, 105�. doi: 10.1016/j.ddmod.2019.08.012

        Wolf, K. (2019). “Vet update on SSP population,” in Proceedings of the Red Wolf Species Survival Plan meeting (Albany, GA).

        Wu, X., Zhang, H., Chen, J., Shang, S., Yan, J., Chen, Y., et al. (2017). Analysis and comparison of the wolf microbiome under different environmental factors using three different data of Next Generation Sequencing. Sci. Rep. 7:11332. doi: 10.1038/s41598-017-11770-4

        Xenoulis, P. G., Palculict, B., Allenspach, K., Steiner, J. M., House, V. M. A., and Suchodolski, J. S. (2008). Molecular-phylogenetic characterization of microbial communities imbalances in the small intestine of dogs with inflammatory bowel disease. FEMS Microbiol. Ecol. 66, 579�. doi: 10.1111/j.1574-6941.2008.00556.x

        Xu, J., Verbrugghe, A., Lourenço, M., Janssens, G. P. J., Liu, D. J. X., Van de Wiele, T., et al. (2016). Does canine inflammatory bowel disease influence gut microbial profile and host metabolism? BMC Vet. Res. 12:114. doi: 10.1186/s12917-016-0736-2

        Yang, T., Santisteban, M. M., Rodriguez, V., Li, E., Ahmari, N., Carvajal, J. M., et al. (2015). Gut dysbiosis is linked to hypertension novelty and significance. Hypertension 65, 1331�. doi: 10.1161/HYPERTENSIONAHA.115.05315

        Yao, R., Xu, L., Hu, T., Chen, H., Qi, D., Gu, X., et al. (2019). The “wildness” of the giant panda gut microbiome and its relevance to effective translocation. Glob. Ecol. Conserv 18:e00644. doi: 10.1016/j.gecco.2019.e00644

        Zhang, H., and Chen, L. (2010). Phylogenetic analysis of 16S rRNA gene sequences reveals distal gut bacterial diversity in wild wolves (Canis lupus). Mol. Biol. Rep. 37, 4013�. doi: 10.1007/s11033-010-0060-z

        Zhu, J., Gao, M., Song, X., Zhao, L., Li, Y., and Hao, Z. (2018b). Changes in bacterial diversity and composition in the faeces and colon of weaned piglets after feeding fermented soybean meal. J. Med. Microbiol. 67, 1181�. doi: 10.1099/jmm.0.000766

        Zhu, L., Wu, Q., Deng, C., Zhang, M., Zhang, C., Chen, H., et al. (2018). Adaptive evolution to a high purine and fat diet of carnivorans revealed by gut microbiomes and host genomes. Environ. Microbiol. 20, 1711�. doi: 10.1111/1462-2920.14096

        Keywords : red wolf, gut microbiome, diet, stool consistency, gastrointestinal health, Canis rufus

        Citation: Bragg M, Freeman EW, Lim HC, Songsasen N and Muletz-Wolz CR (2020) Gut Microbiomes Differ Among Dietary Types and Stool Consistency in the Captive Red Wolf (Canis rufus). Front. Microbiol. 11:590212. doi: 10.3389/fmicb.2020.590212

        Received: 31 July 2020 Accepted: 14 October 2020
        Published: 10 November 2020.

        Gulnaz T. Javan, Alabama State University, United States

        Hu T. Huang, IBM Watson Health, United States
        Jonathan J. Parrott, Arizona State University West Campus, United States

        Copyright © 2020 Bragg, Freeman, Lim, Songsasen and Muletz-Wolz. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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