Probiotics in veterinary practice

Susan G. Wynn Department of Small Animal Clinical Sciences, University of Tennessee, Knoxville, TN 37996.

Search for other papers by Susan G. Wynn in
Current site
Google Scholar
PubMed
Close
 DVM

Probiotics are defined as “live microorganisms which when administered in adequate amounts confer a health benefit on the host.”1 Ideally, probiotics administered to clinically affected patients should originate in the species being treated and should be nonpathogenic, resistant to digestion by gastric acid and intestinal enzymes, able to adhere to the intestinal epithelium, and capable of influencing host immune responses.2

The human gastrointestinal tract contains > 100 trillion organisms comprising approximately 500 species, many of which have not been identified.3 These bacteria are parasites, commensals, or mutualists. Within hours after birth, the gastrointestinal tract is populated with numerous bacterial species, but bifidobacteria predominate in humans.4 The change to a more complex diet after weaning allows the microbial population to diversify.5 Critical differences exist between resident bacteria of humans and other animals.

Each organism strain appears to be associated with specific effects on other organisms and on the host, and specific cytokine profiles and biological effects result from these interactions. Gastrointestinal bacteria have coevolved with their host and have become highly specialized over time. Composition of fecal microbiota in individual humans is unique but stable over time.4 Each host has a unique genetic platform (which expresses disease uniquely) and a unique mixture of indigenous flora that can be considered a fingerprint for that host.

Probiotics have luminal and mucosal effects. Mucosal effects include interactions with immune cells, enterocytes, and goblet cells via cell receptors and cytokine responses. Luminal effects include chemical changes in ingesta and mucus as a result of probiotic activity.

Specific Effects of Probiotics on Hosts

Animals can live without gastrointestinal microbes, but in germ-free animals, certain dietary deficiencies result in more substantial clinical signs than are evident in clinically normal animals.6 Lactobacilli synthesize B vitamins (niacin, pantothenic acid, pyridoxine, biotin, and folic acid) and certain lipolytic and proteolytic digestive enzymes,6 which improves digestibility of food components. Lactobacilli and other enterobacteria also synthesize folate coenzymes that are similar to dietary folate.6 High concentrations of Bacteroides spp may lower serum cobalamin concentrations.7 Clostridium spp, Bacteroides spp, Bifidobacterium spp, and Eubacterium spp deconjugate bile acids efficiently, and high concentrations of these organisms potentially contribute to steatorrhea.8

Ten percent of the daily energy requirements in humans is supplied by microbial activity through anaerobic fermentation.5 Microbial fermentation contributes little to the metabolic energy of cats9 and contributes only approximately 2% to 7% of maintenance energy in dogs.10,11

Survival within the gastrointestinal tract varies among species and even strains of organisms.12 A self-regulating population of gastrointestinal bacteria is maintained through competition, amensalism (ie, a symbiotic relationship between 2 organisms whereby 1 organism is unaffected but the other is negatively affected), parasitism, and predation.4 Specific mechanisms of interaction with other microbes include production of antimicrobial factors, competition for adhesion sites, and production of antitoxins (such as bacteriocin) and decreases in luminal pH.12

In calves, pigs, and poultry, probiotics have increasingly been used to help prevent infection by enteropathogens, such as Salmonella spp and enterotoxigenic Escherichia coli.13–21 Lactic acid–producing bacteria may help control enteropathogenic organisms by producing organic acids within the lumen of the gastrointestinal tract or may compete for attachment sites on the intestinal mucosa.

The gastrointestinal tract is the largest immune organ of the body.22 Germ-free animals have sparse amounts of inactive immune tissues.23 Probiotic organisms interact with the host immune system in a number of ways,12,24 and activation of immune receptors drives nonspecific responses as well as immune responses. Immune cells in the gastrointestinal tract recognize probiotic species types through Toll-like receptors, which leads to specific signal transduction. Cytokine responses characteristic of a specific probiotic species lead to proliferation of responses characteristic of those for T-helper 1 or T-helper 2 cells and modify immunologic tolerance and responsivity. Enhanced humoral immunity, IgA production, and responses to vaccines are examples of these interactions. Probiotics also may play a role in the pathogenesis and management of immune-mediated diseases, such as allergies.

Probiotics may affect the epithelial barrier as well as influence the production of mucus. They can increase brush-border membrane activity, promote epithelial restitution, prevent epithelial apoptosis, protect tight junctions during inflammation (reducing permeability), suppress electrolyte secretion during enteropathogen infection, increase expression of mucin glycoproteins, provide enzymes that may enhance host digestion of dietary nutrients, and shorten gastrointestinal transit time.12,24

Prebiotics

Prebiotics are short- or long-chain oligosaccharides that are not digestible by mammalian digestive enzymes but are fermented in the colon by microorganisms. One example of a prebiotic incorporated into some pet foods is inulin, which is found in the roots of certain plants. Prebiotics reduce pH in the colon because of production of SCFAs as a by-product of the fermentation process; the fermentation process also yields hydrogen and carbon dioxide gases. Prebiotics appear to increase bifidobacteria counts.25 When not fermented, prebiotics will lead to water reabsorption in the colon. One SCFA, butyrate, is the preferred energy source for colonic cells, but the SCFAs probably also have other activities in the colon. Effects of SCFAs include increasing sodium absorption, salvaging energy, increasing mucosal blood flow, regulating cellular proliferation, influencing cell differentiation and carcinogenesis, modulating immune function, and decreasing blood cholesterol concentrations.12

Provision of prebiotics is generally believed to increase numbers of beneficial bacteria.26 However, the ecology of the gastrointestinal tract, which depends on a stringently regulated nutritional and chemical environment, is probably also controlled by other rate-limiting nutrients. These nutrients include iron, small organic molecules, amino acids, lipoic acid, and fatty acids.5

Dietary elements (such as oligosaccharides) strongly influence the growth and replication of bacterial populations in the gastrointestinal tract. Diets high in protein and fat support the growth of Bacteroides spp, peptidococci, and clostridia, whereas a carbohydrate-rich diet supports the growth of bifidobacteria, lactobacilli, eubacteria, and yeasts.5 Several investigators have found that dogs eating dry, grain-based diets have better fecal bacterial profiles (fewer clostridia and more lactic acid–producing organisms), lower fecal pH with higher SCFA concentrations (presumably reflecting higher colonic SCFA concentrations), lower bacterial enzyme activity, and lower concentrations of the putrefactive compounds ammonia, sulfide, and indole.27–30 Canned and possibly low-carbohydrate and grainless raw diets may not support optimal growth of beneficial gastrointestinal bacteria. Dietary supplementation with prebiotics has been evaluated in cats and dogs; however, a thorough review of those studies is beyond the scope of this report.

Role in Disease

Many disease states have now been associated with altered gastrointestinal microbiota, both in predisease and comorbid conditions. In humans, there is good support for the use of probiotics in the treatment of pouchitis and ulcerative colitis,2 inflammatory bowel disease,24 antimicrobial-associated and nosocomial diarrhea,31 and infectious diarrhea.32 There is preliminary evidence to suggest that certain probiotics may help prevent the development of allergies in susceptible children,33–36 improve immune function,37,38 and prevent recurrent urinary tract infections.39 Studies have been conducted to determine whether some probiotics prevent bladder cancer,40 calcium oxalate uroliths,41 pancreatitis,42,43 and pharyngotonsillitis.44

A Study in Healthy Cats

Cats and dogs both have high numbers of bacteria in the proximal portion of the gastrointestinal tract, which are higher than the numbers in the gastrointestinal tract in humans. Cat feces contain high numbers of anaerobes, which are considered abnormal in dogs and humans.45 Of interest in cats, bacterial metabolism of taurine and cobalamin can have relevance in chronic small intestinal disease.

The effects of Lactobacillus acidophilus DSM13241 in 15 healthy adult cats have been evaluated.46 In that study, cats were fed a probiotic-supplemented kibble or plain kibble during separate feeding periods (each cat served as its own control animal). The concentration of bacteria in the kibble equated to an intake of approximately 1.2 × 108 CFUs to 2.8 × 108 CFUs daily. The organisms were sprayed onto the extruded kibble, which was packaged to maintain stability; it was confirmed that there were viable bacteria in the kibble at the conclusion of the study. Mean ± SD fecal pH decreased significantly (P = 0.017) from 6.73 ± 0.34 at baseline to 6.48 ± 0.41 after ingestion of the probiotic-supplemented kibble, and total populations of fecal bifidobacteria decreased significantly (P = 0.036) from 0.16 ± 0.07% to 0.09 ± 0.04% during feeding of the probiotic-supplemented kibble. Clostridium spp decreased significantly (1.27 ± 2.06%; P = 0.003) when cats were eating the probiotic-supplemented kibble, compared with a value of 4.03 ± 1.98% after feeding of the supplemented kibble ended. Similarly, Enterococcus faecalis populations decreased significantly (0.15 ± 0.09% before feeding of the probiotic-supplemented kibble to 0.05 ± 0.06% during feeding of the supplemented kibble; P = 0.001) with use of the supplemented kibble. Clostridial and bifidobacteria numbers increased again after feeding of the probiotic-supplemented kibble ended. Serum immunoglobulin concentrations were unchanged, but granulocyte phagocytic activity (measured by use of fluorescence) increased significantly (from 448.11 ± 126.08 nm at baseline to 780.33 ± 131.61 nm after feeding of the probiotic-supplemented kibble; P = 0.001) and lymphocyte numbers decreased significantly (4.89 ± 1.81 × 109 cells/L at baseline to 4.05 ± 1.69 × 109 cells/L after feeding of the probiotic-supplemented kibble; P = 0.043). Eosinophil numbers also increased significantly (P = 0.002). Erythrocyte fragility decreased significantly (from 17.14 ± 11.32% at baseline to 11.83 ± 9.66% after feeding of the probiotic-supplemented kibble; P = 0.028). Plasma endotoxin concentrations were also reduced during feeding of the supplemented kibble.

Studies in Healthy Dogs

In 1 study,47 investigators isolated a strain of Lactobacillus fermentum (AD1) from a dog and found that after experimentally providing this strain to dogs, serum protein concentration was significantly (P < 0.001) increased by a mean of 1.27 g/dL and serum lipid concentration was significantly (P < 0.01) increased by a mean of 0.15 g/dL. Blood glucose concentration was significantly (P < 0.01) decreased by a mean of 0.7 mmol/L. There were no significant differences in serum cholesterol concentration, alanine aminotransferase activity, or urea concentration. Probiotic bacterial numbers in the feces were significantly (P < 0.001) increased by 3.3 log10 CFUs/g for lactobacilli and by 1.6 log10 CFUs/g for enterococci. In another study,48 investigators cultured 40 strains of enterococci (most of which were strains of Enterococcus faecium) from dog feces, tested them for potential probiotic activity, and determined that E faecalis EE4 and E faecium EF01 were candidates for further study.

Lactobacillus fermentum LAB8, Lactobacillus salivarius LAB9, Lactobacillus rhamnosus LAB11, Lactobacillus mucosae LAB12, and Weissella confusa LAB10 have been cultured from dog feces.49 These organisms were administered for 7 days to dogs with permanent jejunal fistulas. The administered strains disappeared within 7 days after discontinuation of the supplemented diet, but there was a sustained change in the population of indigenous lactic acid–producing bacteria in jejunal contents, with native L acidophilus strains predominating.49

The ability of lactic acid–producing bacteria to interfere with adhesion by enteropathogens was evaluated by use of the intestinal mucus from dogs with permanent jejunal cannulas fed a commercial canned food.50 Strains tested included L rhamnosus GG, Lactobacillus pentosus UK1A, L pentosus SK2A, Bifidobacterium lactis Bb12, E faecium M74, and E faecium SF273. All strains reduced adhesion by Clostridium perfringens (by 53.7% to 79.1%), with those of canine origin interfering the most with adherence. None of the strains altered adhesion by Salmonella enterica serovar Typhimurium or Staphylococcus intermedius, and 2 strains of E faecium actually increased binding by Campylobacter jejuni by 134.6% and 205.5%, respectively, in that study.50

The ability to colonize the intestines and remain viable in the feces are claimed to be prerequisites for determining whether an organism has probiotic properties in a species in which it is not native. In 1 study,51 investigators fed L rhamnosus GG to Beagles at 4 doses. Only at the highest dose (5 × 1011 CFUs/d) was 100% colonization and fecal recovery detected. This dose is considerably higher than that required in humans (6 × 109 CFUs to 1 × 1011 CFUs). No adverse effects were evident in any of the 4 groups of Beagles.51 One popular human producta contains only 2 × 1010 CFUs of L rhamnosus/capsule, which is a high amount when compared with the content in many other over-the-counter products.

Clinical Indications

Inflammatory bowel disease—In diarrheal diseases, the putative mechanisms of benefit from probiotic administration include production of antimicrobial substances (including hydrogen peroxide and acids), competition for nutrients, competitive inhibition of receptor binding, antitoxin activity, and immune stimulation. Dogs with enteropathy for a mean ± SD of 11 ± 3 months were identified at a secondary veterinary medical center and scored by use of the Canine Inflammatory Bowel Disease Activity Index. Endoscopic biopsy specimens were cultured with probiotics of canine origin (L acidophilus NCC2628, L acidophilus NCC2766, and Lactobacillus johnsonii NCC2767), a combination of these 3 probiotics, or a control substance (placebo).22 When used alone, the probiotic strains had no significant effect on cytokine concentrations. However, the combination of the 3 probiotics led to changes in proportions of regulatory and proinflammatory cytokines in ex vivo cultured biopsy specimens. In biopsy specimens obtained from sick dogs, interleukin-10 protein concentrations increased significantly (P < 0.05) when culture medium was stimulated with the probiotic combination (from 70 ± 22 ng/mL in control medium to 161 ± 58 ng/mL in probiotic-stimulated medium). For control dogs, probiotic stimulation of the culture medium resulted in a mean protein concentration of 25 ± 2 ng/mL, which was increased from a mean of 20 ± 11 ng/mL in the control medium.

Fecal and endoscopic biopsy samples were collected from 21 client-owned dogs with food-responsive diarrhea.52 Dogs were then treated with a probiotic cocktail of L acidophilus NCC2628, L acidophilus NCC2766, and L johnsonii NCC2767 or a control substance (placebo), and duodenal cytokines and gastrointestinal microbial populations were examined. All dogs improved clinically on an elimination diet because Canine Inflammatory Bowel Disease Activity Index scores decreased from 5 before placebo treatment to 1 after placebo treatment and from 7 before probiotic treatment to 0 after probiotic treatment.52 Numbers of enterobacteriaceae decreased significantly (P < 0.05) in placebo- and probiotic-fed dogs, but investigators were unable to associate specific cytokine changes with clinical responses or with probiotic treatment.

Diarrhea—One potential benefit from probiotic treatment of animals with diarrhea is to decrease infection by Clostridium difficile, Salmonella spp, and Campylobacter spp. Studies53–55 in food animal species suggest that probiotics can reduce shedding of enteropathogenic bacteria, possibly reducing signs and duration of diarrhea.

Dietary supplementation with E faecium SF68 can be beneficial in adult cats and kittens with chronic diarrhea.56 Thirty-one kittens in a colony developed diarrhea. Approximately half were treated with the probiotic, whereas the others were not. Only 9.5% of the kittens administered the probiotic required additional treatment, compared with 60% of the kittens not administered the probiotic that required additional treatment; these proportions differed significantly (P < 0.05). Diarrhea in the kittens fed the probiotic also resolved significantly (P < 0.05) faster, compared with resolution in the control kittens. Probiotic treatment led to an increase in fecal bifidobacteria, decrease in C perfringens, and increases in blood concentrations of IgA, compared with results for control kittens.

Lactobacillus acidophilus DSM13241 significantly reduces shedding of Campylobacter organisms in infected cats and also reduces reinfection, which reduces the potential for zoonotic transmission.b In that study, 50 cats with clinical signs of infection were administered cephalosporin for 10 days, then given food with or without probiotic (1 × 109 CFUs) for 4 weeks. The increase in Campylobacter organisms as a percentage of total fecal bacteria was significantly (P < 0.05) smaller in cats administered the probiotic (12.2% in probiotictreated cats vs 19.7% in untreated cats). At the end of the study, probiotic-treated cats had eliminated significantly (P < 0.05) more Campylobacter organisms (as a percentage of total bacterial population) than did control cats (3.94% vs 14.06%, respectively).

Effects of a product containing E faecium NCIB 10415c (also known as E faecium SF68) on numbers of fecal Salmonella spp, Campylobacter spp, and Clostridium spp were evaluated in 12 client-owned dogs.57 The daily dose was 9.2 × 109 CFUs, which was administered for 18 days, regardless of each dog's body weight. Although bacterial counts varied widely among dogs, there was a pattern for increases in Salmonella spp and Campylobacter spp when dogs were provided with the E faecium product (counts on some dogs were higher, whereas counts in other dogs were lower). However, numbers of clostridial organisms were significantly (P < 0.05) decreased.57 In baby pigs, this strain of E faecium can decrease the pathogenic effects of E coli with no effect on fecal E coli counts.21

General immune function—Results of studies58–61 conducted by use of different organisms in a variety of laboratory animals and humans suggest that many probiotic species can influence immune function. Administration of E faecium SF68 (5 × 108 CFUs daily) to puppies from time of weaning to 1 year of age had effects on immune function. Fourteen puppies were allocated into 2 groups and fed a commercial diet, with or without the probiotic, for 1 year.62 Total fecal IgA concentration typically was higher, but not significantly so (P = 0.056), in the dogs administered the probiotic in their diet, compared with results for dogs fed the diet alone. Beginning when the dogs were 18 weeks old, plasma IgA concentration was higher in the dogs fed the probiotic in their diet, whereas plasma IgG concentrations did not differ between the groups. Response to distemper vaccination (measured as canine distemper virus–specific IgG and IgA content) was significantly (P < 0.05) stronger in the treatment group. There was also a greater proportion of mature B cells in dogs fed the probiotic (mean ± SD, 16 ± 1.6% vs 11.5 ± 1.5% in the treated and control dogs, respectively), whereas T-cell populations were not different between the 2 groups. Amounts of food-specific IgE were not different between probiotic and control groups, which suggested that the effects on immunoglobulins and B cells were not attributable to immune dysregulation. The investigators determined that these effects were attributable to immunomodulation by E faecium SF68, as opposed to changes that were attributable to manipulation of the bacterial population.62

Chronic renal disease—Uremic toxins diffuse passively from the blood into the lumen of the gastrointestinal tract. Urease-producing probiotic species hydrolyze urea and maintain a concentration gradient that favors diffusion of urea from the blood to the gastrointestinal tract lumen. Studies in rats63,64 and pigsd that involved use of a patented producte (a combination of Enterococcus thermophilus, L acidophilus, and Bifidobacterium longum) revealed that administration of the product reduces uremia and number of fatalities. A case series of 7 azotemic cats at a private clinical practice was reported.65 After administration of a probiotic for 60 days, all cats had a decrease in BUN concentrations and 6 of 7 had a decrease in serum creatinine concentrations. Concurrent treatments varied among the cats, and the medical history of each cat was not reported. Only 1 cat apparently received probiotic administration alone; that cat was fed a commercial food and did not receive parenterally administered fluids. Although the serum creatinine concentration was reduced from 2.6 to 2.2 mg/dL, the cat lost weight (0.23 kg [0.5 lb]).65

Pancreatitis—Translocation of gastrointestinal bacteria during pancreatitis can lead to septicemia and substantially worsen a patient's prognosis. Results of studies43,66–70 conducted in humans and other animals by use of Lactobacillus plantarum 299, Saccharomyces boulardii, and combinations of probiotics and prebiotics suggest that probiotic administration may be of benefit in patients with acute necrotizing pancreatitis. Probiotic organisms appear to improve the intestinal barrier, which prevents bacterial translocation, and lactic acid–producing bacteria can suppress the inflammation that makes systemic inflammation response syndrome such a deadly condition in patients with acute pancreatitis.

Investigators have conducted studies71,72 in dogs with experimentally induced severe pancreatitis. Affected dogs have been provided nutrients parenterally as well as elemental enteral nutrition or dietary supplementation with probiotics. In 1 study,71 increases in serum activity of amylase, alanine aminotransferase, and aspartate aminotransferase and plasma concentrations of endotoxin, as well as pancreatic and ileal histopathologic changes, were significantly (P < 0.05) suppressed with probiotic administration. The degree of bacterial translocation was significantly (P < 0.05) decreased with probiotic administration, which suggested that this probiotic combination (described as 40 mg of Lactobacillus spp and 40 mg of Bifidobacterium spp) enhanced gastrointestinal barrier function.71 Investigators in another study72 obtained similar results.

Safety

Authors of a review73 published in 2004 found 23 probiotic species of Lactobacillus involved in 89 severely ill humans with lactobacilli bacteremia. Predisposing factors were immunosuppression, prior prolonged hospitalization, and prior surgical interventions. On the other hand, a randomized, double-blind, placebo-controlled trial74 in critically ill humans revealed that the patients were not more prone to adverse effects from probiotic administration, they had significant increases in systemic IgA and IgG concentrations, and their intestinal permeability was decreased. Lactobacillus rhamnosus GG has been associated with bacteremia after administration to a child with short gut syndrome.75 It has also been suggested that Lactobacillus spp produce organic acids that may lead to decalcification of dental matrix.76

A number of cases (92 cases as of 2005) of invasive infection in humans attributable to S boulardii (a subspecies of Saccharomyces cerevisiae) have been reported, usually when the S boulardii was administered to patients with diarrhea. Intravascular catheter placement and antimicrobial treatment are common features in these patients.77 Septicemia attributable to ingestion of a probiotic strain of Bacillus subtilis was reported78 in a 73-year-old person with leukemia.

To the author's knowledge, septicemia following dietary supplementation of companion animals with probiotic organisms has not been reported. Caution is advised if dietary supplementation is considered in severely immunosuppressed or critically ill animals or in animals in which marked compromise of the intestinal mucosa is suspected.

Quality Control of Probiotic Products

Commercial probiotic products have large variations in quality control. Problems may range from viability issues to inclusion of species not listed on the label.

In 1 study,79 health food store products labeled for use in humans in Canada commonly contained (in addition to the organism on the label) a strain of Lactobacillus spp not listed on the label. An analysis of over-the-counter brands of probiotic found that of 13 human products sampled, 4 did not contain the amount listed on the label and 4 did not contain the generally accepted effective dose of at least 109 organisms.79 None of the 13 human products had microbial contamination. Of 3 over-the-counter products formulated for use in domestic animals, 1 did not contain the amount claimed on the label, 2 did not contain the recommended 109 organisms/daily dose, and 1 was contaminated with mold.79

In another study,80 23 over-the-counter probiotic products formulated for use in animals and 21 products formulated for use in humans were evaluated to determine their adherence with label claims. Bacterial species were misspelled (in up to 25% of products), and bacterial species were frequently misidentified (outdated names of organisms or names of nonexistent organisms). Only 5 of the veterinary products provided information about the intended number of probiotic organisms, often without clarification as to the date on which that number should be expected. Because of the deficiencies identified in that study,80 practitioners and consumers should expect a probiotic product label to include the organisms (included down to the strain level), correct spelling and identification of all organisms in the product, and number of live organisms expected on the expiration date. In another study,81 analysis of the labels for 5 products on the European market yielded similar results.

Holistic commercial diets formulated for dogs and cats sometimes list probiotics among their ingredients. Thirteen commercial diets for dogs and 6 commercial diets for cats, all of which claimed to contain probiotics, were analyzed for the content of species listed on the labels.82 Twelve diets did not list a live organism (which is needed to be consistent with the claim to contain a probiotic); instead, they listed probiotic fermentation products. The FDA recommends labeling probiotics as feed ingredients with the term bacterial fermentation products; however, this term does not indicate whether organisms are viable. Only 7 of the diets contained at least 1 of the listed species, and none contained all of the probiotics listed on their labels. Lactobacillus acidophilus was listed in labels of 13 of the diets but was not cultured from any of them. Bifidobacterium spp, which are anaerobic organisms, were not cultured from any product that claimed to contain them. The diets contained < 1.8 × 105 CFUs/g, which suggested that approximately 5.5 kg (12.1 lb) of diet would need to be consumed daily to reach dose amounts believed to be necessary to provide clinical probiotic effects. The survival of Bacillus CIP 5832 was investigated.82 Investigators in that study found that extrusion significantly reduced the number of viable spores, although coating the food with a powder of the probiotic after extrusion better preserved the viability.

Investigators in 1 study83 added L acidophilus to dog food. Initial recovery was 71%, with recovery of 63% 8 weeks later. In that study, dogs of various breeds and ages were fed a control food without probiotics for 2 weeks, then given the supplemented food for 4 weeks, and finally given the control food again for an additional 2 weeks. The daily dose was 109 CFUs, which was incorporated into the food by adding freeze-dried organisms in oil after extrusion of the kibble. During the period when they ate the supplemented food, the dogs had increased numbers of fecal lactobacilli and decreased numbers of clostridia, changes that were reversed when the control diet was again administered. Feeding of the supplemented diet led to significant increases in RBCs (from 6.22 ± 0.61 × 1012 cells/L when fed the control food to 6.79 ± 2.39 × 1012 cells/L when fed the supplemented food [P = 0.002]), neutrophils (from 3.20 ± 1.05 × 109 cells/L when fed the control food to 3.58 ± 0.87 × 109 cells/L when fed the supplemented food [P = 0.033]), and monocytes (from 0.34 ± 0.13 × 109 cells/L when fed the control food to 0.52 ± 0.29 × 109 cells/L when fed the supplemented food [P = 0.012]). Hematocrit increased significantly (P < 0.001) from 0.45 ± 0.004 L/L when dogs ate the control food to 0.50 ± 0.003 L/L when dogs ate the supplemented food. Hemoglobin concentrations increased significantly (P = 0.003) from 14.97 ± 1.17 g/dL when dogs ate the control food to 15.97 ± 0.88 g/dL when dogs ate the supplemented food. Concentrations of IgG increased significantly (P = 0.010) from 18.2 ± 4.2 mg/mL when dogs ate the control food to 21.4 ± 5.0 mg/mL when dogs ate the supplemented food. Nitric oxide concentration decreased significantly (P < 0.001) from 13.98 ± 8.36mM when dogs ate the control food to 3.67 ± 2.39mM when dogs ate the supplemented food. Finally, RBC fragility decreased significantly (P < 0.001) from 56.6 ± 26.6% when dogs ate the control food to 39.1 ± 31.4% when dogs ate the supplemented food. The investigators processed the food for minimal moisture content (2%), stored it in aluminum bags, provided the food to the dogs in dry form without adding water, and minimized exposure to moisture while it was available to the dogs, thus maximizing the dose.

Debate exists about the value of nonviable probiotic bacteria. In 2 recent clinical studies,84,85 it has been suggested that nonviable organisms do not have probiotic effects. Nonviable bacteria, bacterial DNA components, and media from probiotic cultures have had beneficial effects in animals with induced colitis and in knockout mice predisposed to colitis.2 On the other hand, a study84 in which investigators used heat-inactivated L rhamnosus GG was terminated prematurely because of adverse effects on the gastrointestinal tract.

Conclusions

Probiotic products are subject to variations in quality control, and the safety profile is still under investigation. The regulatory situation is similarly unclear because the FDA considers probiotic products labeled with medical indications for animals to be unapproved drugs.

However, it is increasingly clear that manipulation of the ecology of the gastrointestinal tract has powerful systemic effects. Use of probiotics clearly enhances immune function in a number of species, including dogs and cats, and appears to have a role in the treatment of animals with certain gastrointestinal conditions. Other clinical effects (such as prevention of recurrent urinary tract infections, prevention and treatment of allergies, and treatment of pancreatitis, oxalate urolithiasis, and other conditions) have been investigated in humans, which suggests a range of potential benefits in veterinary patients.

Abbreviations

CFU

Colony-forming unit

SCFA

Short-chain fatty acid

References

  • 1.

    Nomoto K. Prevention of infections by probiotics. J Biosci Bioeng 2005;100:583592.

  • 2.

    Dotan I, Rachmilewitz D. Probiotics in inflammatory bowel disease: possible mechanisms of action. Curr Opin Gastroenterol 2005;21:426430.

    • Search Google Scholar
    • Export Citation
  • 3.

    Isolauri E, Salminen S. Probiotics, gut inflammation and barrier function. Gastroenterol Clin North Am 2005;34:437450.

  • 4.

    Tannock GW. New perceptions of the gut microbiota: implications for future research. Gastroenterol Clin North Am 2005;34:361382.

  • 5.

    Schaible UE, Kaufmann SH. A nutritive view on the host-pathogen interplay. Trends Microbiol 2005;13:373380.

  • 6.

    Shahani KM, Ayeb AD. Role of dietary lactobacilli in gastrointestinal microecology. Am J Clin Nutr 1980;33 (suppl 11):24482457.

  • 7.

    Welkos SL, Toskes PP, Baer H. Importance of anaerobic bacteria in the cobalamin malabsorption of the experimental rat blind loop syndrome. Gastroenterology 1981;80:313320.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 8.

    Takahashi M, Maeda Y, Tashiro H, et al. A new simple test for evaluation of intestinal bacteria. World J Surg 1990;14:628634.

  • 9.

    Brosey BP, Hill RC, Scott KC. Gastrointestinal volatile fatty acid concentrations and pH in cats. Am J Vet Res 2000;61:359361.

  • 10.

    Stevens CS, Hume ID. Contributions of microbes in vertebrate gastrointestinal tract to production and conservation of nutrients. Physiol Rev 1998;78:393427.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 11.

    Herschel DA, Argenzio RA, Southworth M, et al. Absorption of volatile fatty acid, Na, and H2O by the colon of the dog. Am J Vet Res 1981;42:11181124.

    • Search Google Scholar
    • Export Citation
  • 12.

    Marteau P, Seksik P, Lepage P, et al. Cellular and physiological effects of probiotics and prebiotics. Mini Rev Med Chem 2004;4:889896.

  • 13.

    Van Immerseel F, Russell JB, Flythe MD, et al. The use of organic acids to combat Salmonella in poultry: a mechanistic explanation of the efficacy. Avian Pathol 2006;35:182188.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 14.

    Nava GM, Castaneda MP, Juarez MA. Effective probiotic therapy (lett). Clin Nutr 2005;24:478.

  • 15.

    Timmerman HM, Veldman A, van den Elsen E, et al. Mortality and growth performance of broilers given drinking water supplemented with chicken-specific probiotics. Poult Sci 2006;85:13831388.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 16.

    Zhao T, Tkalcic S, Doyle MP, et al. Pathogenicity of enterohemorrhagic Escherichia coli in neonatal calves and evaluation of fecal shedding by treatment with probiotic Escherichia coli. J Food Prot 2003;66:924930.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 17.

    Ohya T, Marubashi T, Ito H. Significance of fecal volatile fatty acids in shedding of Escherichia coli O157 from calves: experimental infection and preliminary use of a probiotic product. J Vet Med Sci 2000;62:11511155.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 18.

    Zhao T, Doyle MP, Harmon BG, et al. Reduction of carriage of enterohemorrhagic Escherichia coli O157:H7 in cattle by inoculation with probiotic bacteria. J Clin Microbiol 1998;36:641647.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 19.

    Kyriakis SC, Tsiloyiannis VK, Vlemmas J, et al. The effect of probiotic LSP 122 on the control of post-weaning diarrhoea syndrome of piglets. Res Vet Sci 1999;67:223228.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 20.

    Schroeder B, Duncker S, Barth S, et al. Preventive effects of the probiotic Escherichia coli strain Nissle 1917 on acute secretory diarrhea in a pig model of intestinal infection. Dig Dis Sci 2006;51:724731.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 21.

    Underdahl NR. The effect of feeding Streptococcus faecium upon Escherichia coli induced diarrhea in gnotobiotic pigs. Prog Food Nutr Sci 1983;7:512.

    • Search Google Scholar
    • Export Citation
  • 22.

    Sauter SN, Allenspach K, Gaschen F, et al. Cytokine expression in an ex vivo culture system of duodenal samples from dogs with chronic enteropathies: modulation by probiotic bacteria. Domest Anim Endocrinol 2005;29:605622.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 23.

    MacDonald TT, Gordon JN. Bacterial regulation of intestinal immune responses. Gastroenterol Clin North Am 2005;34:401412.

  • 24.

    Rioux KP, Madsen KL, Fedorak RN. The role of enteric microflora in inflammatory bowel disease: human and animal studies with probiotics and prebiotics. Gastroenterol Clin North Am 2005;34:465482.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 25.

    Schell MA, Karmirantzou M, Snel B, et al. The genome sequence of Bifidobacterium longum reflects its adaptation to the human gastrointestinal tract. Proc Natl Acad Sci U S A 2002;99:1442214427.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 26.

    Gibson GR, Roberfroid MB. Dietary modulation of the colonic microbiota: introducing the concept of prebiotics. J Nutr 1995;125:14011412.

  • 27.

    Zentek J, Van der Steen I, Rohde J, et al. Dietary effects of the occurrence and enterotoxin production of Clostridium perfringens in the canine. J Anim Physiol Anim Nutr (Berl) 1998;80:250252.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 28.

    Zentek J, Marquart B, Pietrzak T, et al. Dietary effects on bifidobacteria and Clostridium perfringens in the canine intestinal tract. J Anim Physiol Anim Nutr (Berl) 2003;87:397407.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 29.

    Banta CA, Clemens ET, Krinsky MM, et al. Sites of organic acid production and patterns of digesta movement in the gastrointestinal tract of dogs. J Nutr 1979;109:15921600.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 30.

    Martineau B, Laflamme DP. Effect of diet on markers of intestinal health. Res Vet Sci 2002;72:223227.

  • 31.

    de Vrese M, Marteau PR. Probiotics and prebiotics: effects on diarrhea. J Nutr 2007;137:803S811S.

  • 32.

    Allen SJ, Okoko B, Martinez E, et al. Probiotics for treating infectious diarrhoea. Cochrane Database Syst Rev 2004;2:CD003048.

  • 33.

    Majamaa H, Isolauri E. Probiotics: a novel approach in patients with food allergy. J Allergy Clin Immunol 1997;99:179185.

  • 34.

    Isolauri E, Arvola T, Sutas Y, et al. Probiotics in the management of atopic eczema. Clin Exp Allergy 2000;30:16041610.

  • 35.

    Rosenfeldt V, Benfeldt E, Nielsen SD, et al. Effect of probiotic Lactobacillus strains in children with atopic dermatitis. J Allergy Clin Immunol 2003;111:389395.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 36.

    Kalliomaki M, Salminen S, Poussa T, et al. Probiotics and prevention of atopic disease: 4-year follow-up of a randomized placebo-controlled trial. Lancet 2003;361:18691871.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 37.

    Gill HS, Darragh AJ, Cross ML. Optimizing immunity and gut function in the elderly. J Nutr Health Aging 2001;5:8091.

  • 38.

    Isolauri E, Joensuu J, Suomalainen H, et al. Improved immunogenicity of oral D × RRv reassortant rotavirus vaccine by Lactobacillus casei GG. Vaccine 1995;13:310312.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 39.

    Reid G, Bruce AW. Probiotics to prevent urinary tract infections: the rationale and evidence. World J Urol 2006;24:2832.

  • 40.

    Ohashi Y, Nakai S, Tsukamoto T, et al. Habitual intake of lactic acid bacteria and risk reduction of bladder cancer. Urol Int 2002;68:273280.

  • 41.

    Hoppe B, Beck B, Gatter N, et al. Oxalobacter formigenes: a potential tool for the treatment of primary hyperoxaluria type 1. Kidney Int 2006;70:13051311.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 42.

    Bengmark S. Bio-ecological control of acute pancreatitis: the role of enteral nutrition, pro and synbiotics. Curr Opin Clin Nutr Metab Care 2005;8:557561.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 43.

    Olah A, Belagyi T, Issekutz A, et al. Randomized clinical trial of specific lactobacillus and fibre supplement to early enteral nutrition in patients with acute pancreatitis. Br J Surg 2002;89:11031107.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 44.

    Roos K, Holm S. The use of probiotics in head and neck infections. Curr Infect Dis Rep 2002;4:211216.

  • 45.

    Johnston K, Lamport A, Batt RM. An unexpected bacterial flora in the proximal small intestine of normal cats. Vet Rec 1993;132:362363.

  • 46.

    Marshall-Jones ZV, Baillon ML, Croft JM, et al. Effects of Lactobacillus acidophilus DSM13241 as a probiotic in healthy adult cats. Am J Vet Res 2006;67:10051012.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 47.

    Strompfova V, Marcinakova M, Simonova M, et al. Application of potential probiotic Lactobacillus fermentum AD1 strain in healthy dogs. Anaerobe 2006;12:7579.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 48.

    Strompfova V, Laukova A, Ouwehand AC. Lactobacilli and enterococci—potential probiotics for dogs. Folia Microbiol (Praha) 2004;49:203207.

  • 49.

    Manninen TJK, Rinkinen ML, Beasley SS, et al. Alteration of the canine small-intestinal lactic acid bacterium microbiota by feeding of potential probiotics. Appl Environ Microbiol 2006;72:65396543.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 50.

    Rinkinen M, Jalava K, Westermarck E, et al. Interaction between probiotic lactic acid bacteria and canine enteric pathogens: a risk factor for intestinal Enterococcus faecium colonization? Vet Microbiol 2003;92:111119.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 51.

    Weese JS, Anderson RE. Preliminary evaluation of Lactobacillus rhamnosus strain GG, a potential probiotic in dogs. Can Vet J 2002;43:771774.

    • Search Google Scholar
    • Export Citation
  • 52.

    Sauter SN, Benyacoub J, Allenspach K, et al. Effects of probiotic bacteria in dogs with food responsive diarrhoea treated with an elimination diet. J Anim Physiol Anim Nutr (Berl) 2006;90:269277.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 53.

    Nava GM, Bielke LR, Callaway TR, et al. Probiotic alternatives to reduce gastrointestinal infections: the poultry experience. Anim Health Res Rev 2005;6:105118.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 54.

    Lallès JP, Bosi P, Smidt H, et al. Nutritional management of gut health in pigs around weaning. Proc Nutr Soc 2007;66:260268.

  • 55.

    Sargeant JM, Amezcua MR, Waddell L, et al. Pre-harvest interventions to reduce the shedding of E. coli O157 in the faeces of weaned domestic ruminants: a systematic review. Zoonoses Public Health 2007;54:260277.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 56.

    Czarnecki-Maulden GL, Cavadini C, Lawler D. The role of probiotics in GI tract health. St Louis: Nestlé Purina, 2006.

  • 57.

    Vahjen W, Manner K. The effect of a probiotic Enterococcus faecium product in diets of healthy dogs on bacteriological counts of Salmonella spp., Campylobacter spp. and Clostridium spp. in faeces. Arch Tierernahr 2003;57:229233.

    • Search Google Scholar
    • Export Citation
  • 58.

    Bauer E, Williams BA, Smidt H, et al. Influence of the gastrointestinal microbiota on development of the immune system in young animals. Curr Issues Intest Microbiol 2006;7:3551.

    • Search Google Scholar
    • Export Citation
  • 59.

    Liong MT. Probiotics: a critical review of their potential role as antihypertensives, immune modulators, hypocholesterolemics, and perimenopausal treatments. Nutr Rev 2007;68:316328.

    • Search Google Scholar
    • Export Citation
  • 60.

    Madsen IK. Probiotics and the immune response. J Clin Gastroenterol 2006;40:232234.

  • 61.

    Corthésy B, Gaskins HR, Mercenier A. Cross-talk between probiotic bacteria and the host immune system. J Nutr 2007;137 (suppl 2):781S790S.

  • 62.

    Benyacoub J, Czarnecki-Maulden GL, Cavadini C, et al. Supplementation of food with Enterococcus faecium (SF68) stimulates immune functions in young dogs. J Nutr 2003;133:11581162.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 63.

    Ranganathan N, Patel B, Ranganathan P, et al. Probiotic amelioration of azotemia in 5/6th nephrectomized Sprague-Dawley rats. Sci World J 2005;5:652660.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 64.

    Ranganathan N, Patel BG, Ranganathan P, et al. In vitro and in vivo assessment of intraintestinal bacteriotherapy in chronic kidney disease. ASAIO J 2006;52:7079.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 65.

    Palmquist R. A preliminary clinical evaluation of Kibow Biotics®, a probiotic agent, on feline azotemia. J Am Holistic Vet Med Assoc 2006;24:2327.

    • Search Google Scholar
    • Export Citation
  • 66.

    Sahin T, Aydin S, Yuksel O, et al. Effects of the probiotic agent Saccharomyces boulardii on the DNA damage in acute necrotizing pancreatitis induced rats. Hum Exp Toxicol 2007;26:653661.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 67.

    Muftuoglu MA, Isikgor S, Tosun S, et al. Effects of probiotics on the severity of experimental acute pancreatitis. Eur J Clin Nutr 2006;60:464468.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 68.

    Kecskés G, Belágyi T, Oláh A. Early jejunal nutrition with combined pre- and probiotics in acute pancreatitis—prospective, randomized, double-blind investigations [in Hungarian]. Magy Seb 2003;56:38.

    • Search Google Scholar
    • Export Citation
  • 69.

    Mangiante G, Colucci G, Canepari P, et al. Lactobacillus plantarum reduces infection of pancreatic necrosis in experimental acute pancreatitis. Dig Surg 2001;18:4750.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 70.

    van Minnen LP, Timmerman HM, Lutgendorff F, et al. Modification of intestinal flora with multispecies probiotics reduces bacterial translocation and improves clinical course in a rat model of acute pancreatitis. Surgery 2007;141:470480.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 71.

    Xu GF, Lu Z, Gao J, et al. Effect of ecoimmunonutrition supports on maintenance of integrity of intestinal mucosal barrier in severe acute pancreatitis in dogs. Chin Med J (Engl) 2006;119:656661.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 72.

    Qin HL, Su ZD, Gao Q, et al. Early intrajejunal nutrition: bacterial translocation and gut barrier function of severe acute pancreatitis in dogs. Hepatobiliary Pancreat Dis Int 2002;1:150154.

    • Search Google Scholar
    • Export Citation
  • 73.

    Salminen MK, Rautelin H, Tynkkyne S, et al. Lactobacillus bacteremia, clinical significance, and patient outcome, with special focus on probiotic L. rhamnosus GG. Clin Infect Dis 2004;38:6269.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 74.

    Alberda C, Gramlich L, Meddings J, et al. Effects of probiotic therapy in critically ill patients: a randomized, double-blind, placebo-controlled trial. Am J Clin Nutr 2007;85:816823.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 75.

    De Groote MA, Frank DN, Dowell E, et al. Lactobacillus rhamnosus GG bacteremia associated with probiotic use in a child with short gut syndrome. Pediatr Infect Dis J 2005;24:278280.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 76.

    Montalto M, Vastola M, Marigo L, et al. Probiotic treatment increases salivary counts of lactobacilli: a double-blind, randomized, controlled study. Digestion 2004;69:5356.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 77.

    Enache-Angoulvant A, Hennequin C. Invasive Saccharomyces infection: a comprehensive review. Clin Infect Dis 2005;41:15591568.

  • 78.

    Oggioni MR, Pozzi G, Valensin PE, et al. Recurrent septicemia in an immunocompromised patient due to probiotic strains of Bacillus subtilis. J Clin Microbiol 1998;36:325326.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 79.

    Product Review. Probiotic supplements (including Lactobacillus acidophilus, Bifidobacterium, and others). Available at: www.ConsumerLab.com. Accessed Feb 12, 2007.

    • Search Google Scholar
    • Export Citation
  • 80.

    Weese JS. Microbiologic evaluation of commercial probiotics. J Am Vet Med Assoc 2002;220:794797.

  • 81.

    Lata J, Juránková J, Doubek J, et al. Labelling and content evaluation of commercial veterinary probiotics. Acta Vet (Brno) 2006;75:139144.

  • 82.

    Weese JS, Arroyo L. Bacteriological evaluation of dog and cat diets that claim to contain probiotics. Can Vet J 2003;44:212216.

  • 83.

    Biourge V, Vallet C, Levesque A, et al. The use of probiotics in the diet of dogs. J Nutr 2007;128 (suppl 12):2730S2732S.

  • 84.

    Briand V, Buffet P, Genty S, et al. Absence of efficacy of nonviable Lactobacillus acidophilus for the prevention of traveler's diarrhea: a randomized, double-blind, controlled study. Clin Infect Dis 2006;43:11701175.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 85.

    Sanders ME, Hamilton J, Reid G, et al. A nonviable preparation of Lactobacillus acidophilus is not a probiotic (lett). Clin Infect Dis 2007;44:886.

a.

Culturelle, Amerifit Brands Inc, Cromwell, Conn.

b.

Baillon ML, Butterwick RF. The efficacy of a probiotic strain, Lactobacillus acidophilus DSM13241, in the recovery of cats from clinical Campylobacter infection (abstr), in Proceedings. 21st Annu Forum Am Coll Vet Intern Med Conf 2003. Available at: www.vin.com/Members/Proceedings/Proceedings.plx?CID=acvim2003&PID=pr04140&O=VIN. Accessed Dec 7, 2008.

c.

Enteroferm, Fendigo sa/nv, Brussels, Belgium.

d.

Ranganathan N, Patel B, Ranganathan P. Probiotic reduces azotemia in Gottingen Minipig (poster presentation). 3rd World Cong Nephrol, Singapore, June, 2005.

e.

Azodyl, Vetoquinol SA, Lure, France.

  • 1.

    Nomoto K. Prevention of infections by probiotics. J Biosci Bioeng 2005;100:583592.

  • 2.

    Dotan I, Rachmilewitz D. Probiotics in inflammatory bowel disease: possible mechanisms of action. Curr Opin Gastroenterol 2005;21:426430.

    • Search Google Scholar
    • Export Citation
  • 3.

    Isolauri E, Salminen S. Probiotics, gut inflammation and barrier function. Gastroenterol Clin North Am 2005;34:437450.

  • 4.

    Tannock GW. New perceptions of the gut microbiota: implications for future research. Gastroenterol Clin North Am 2005;34:361382.

  • 5.

    Schaible UE, Kaufmann SH. A nutritive view on the host-pathogen interplay. Trends Microbiol 2005;13:373380.

  • 6.

    Shahani KM, Ayeb AD. Role of dietary lactobacilli in gastrointestinal microecology. Am J Clin Nutr 1980;33 (suppl 11):24482457.

  • 7.

    Welkos SL, Toskes PP, Baer H. Importance of anaerobic bacteria in the cobalamin malabsorption of the experimental rat blind loop syndrome. Gastroenterology 1981;80:313320.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 8.

    Takahashi M, Maeda Y, Tashiro H, et al. A new simple test for evaluation of intestinal bacteria. World J Surg 1990;14:628634.

  • 9.

    Brosey BP, Hill RC, Scott KC. Gastrointestinal volatile fatty acid concentrations and pH in cats. Am J Vet Res 2000;61:359361.

  • 10.

    Stevens CS, Hume ID. Contributions of microbes in vertebrate gastrointestinal tract to production and conservation of nutrients. Physiol Rev 1998;78:393427.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 11.

    Herschel DA, Argenzio RA, Southworth M, et al. Absorption of volatile fatty acid, Na, and H2O by the colon of the dog. Am J Vet Res 1981;42:11181124.

    • Search Google Scholar
    • Export Citation
  • 12.

    Marteau P, Seksik P, Lepage P, et al. Cellular and physiological effects of probiotics and prebiotics. Mini Rev Med Chem 2004;4:889896.

  • 13.

    Van Immerseel F, Russell JB, Flythe MD, et al. The use of organic acids to combat Salmonella in poultry: a mechanistic explanation of the efficacy. Avian Pathol 2006;35:182188.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 14.

    Nava GM, Castaneda MP, Juarez MA. Effective probiotic therapy (lett). Clin Nutr 2005;24:478.

  • 15.

    Timmerman HM, Veldman A, van den Elsen E, et al. Mortality and growth performance of broilers given drinking water supplemented with chicken-specific probiotics. Poult Sci 2006;85:13831388.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 16.

    Zhao T, Tkalcic S, Doyle MP, et al. Pathogenicity of enterohemorrhagic Escherichia coli in neonatal calves and evaluation of fecal shedding by treatment with probiotic Escherichia coli. J Food Prot 2003;66:924930.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 17.

    Ohya T, Marubashi T, Ito H. Significance of fecal volatile fatty acids in shedding of Escherichia coli O157 from calves: experimental infection and preliminary use of a probiotic product. J Vet Med Sci 2000;62:11511155.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 18.

    Zhao T, Doyle MP, Harmon BG, et al. Reduction of carriage of enterohemorrhagic Escherichia coli O157:H7 in cattle by inoculation with probiotic bacteria. J Clin Microbiol 1998;36:641647.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 19.

    Kyriakis SC, Tsiloyiannis VK, Vlemmas J, et al. The effect of probiotic LSP 122 on the control of post-weaning diarrhoea syndrome of piglets. Res Vet Sci 1999;67:223228.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 20.

    Schroeder B, Duncker S, Barth S, et al. Preventive effects of the probiotic Escherichia coli strain Nissle 1917 on acute secretory diarrhea in a pig model of intestinal infection. Dig Dis Sci 2006;51:724731.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 21.

    Underdahl NR. The effect of feeding Streptococcus faecium upon Escherichia coli induced diarrhea in gnotobiotic pigs. Prog Food Nutr Sci 1983;7:512.

    • Search Google Scholar
    • Export Citation
  • 22.

    Sauter SN, Allenspach K, Gaschen F, et al. Cytokine expression in an ex vivo culture system of duodenal samples from dogs with chronic enteropathies: modulation by probiotic bacteria. Domest Anim Endocrinol 2005;29:605622.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 23.

    MacDonald TT, Gordon JN. Bacterial regulation of intestinal immune responses. Gastroenterol Clin North Am 2005;34:401412.

  • 24.

    Rioux KP, Madsen KL, Fedorak RN. The role of enteric microflora in inflammatory bowel disease: human and animal studies with probiotics and prebiotics. Gastroenterol Clin North Am 2005;34:465482.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 25.

    Schell MA, Karmirantzou M, Snel B, et al. The genome sequence of Bifidobacterium longum reflects its adaptation to the human gastrointestinal tract. Proc Natl Acad Sci U S A 2002;99:1442214427.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 26.

    Gibson GR, Roberfroid MB. Dietary modulation of the colonic microbiota: introducing the concept of prebiotics. J Nutr 1995;125:14011412.

  • 27.

    Zentek J, Van der Steen I, Rohde J, et al. Dietary effects of the occurrence and enterotoxin production of Clostridium perfringens in the canine. J Anim Physiol Anim Nutr (Berl) 1998;80:250252.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 28.

    Zentek J, Marquart B, Pietrzak T, et al. Dietary effects on bifidobacteria and Clostridium perfringens in the canine intestinal tract. J Anim Physiol Anim Nutr (Berl) 2003;87:397407.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 29.

    Banta CA, Clemens ET, Krinsky MM, et al. Sites of organic acid production and patterns of digesta movement in the gastrointestinal tract of dogs. J Nutr 1979;109:15921600.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 30.

    Martineau B, Laflamme DP. Effect of diet on markers of intestinal health. Res Vet Sci 2002;72:223227.

  • 31.

    de Vrese M, Marteau PR. Probiotics and prebiotics: effects on diarrhea. J Nutr 2007;137:803S811S.

  • 32.

    Allen SJ, Okoko B, Martinez E, et al. Probiotics for treating infectious diarrhoea. Cochrane Database Syst Rev 2004;2:CD003048.

  • 33.

    Majamaa H, Isolauri E. Probiotics: a novel approach in patients with food allergy. J Allergy Clin Immunol 1997;99:179185.

  • 34.

    Isolauri E, Arvola T, Sutas Y, et al. Probiotics in the management of atopic eczema. Clin Exp Allergy 2000;30:16041610.

  • 35.

    Rosenfeldt V, Benfeldt E, Nielsen SD, et al. Effect of probiotic Lactobacillus strains in children with atopic dermatitis. J Allergy Clin Immunol 2003;111:389395.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 36.

    Kalliomaki M, Salminen S, Poussa T, et al. Probiotics and prevention of atopic disease: 4-year follow-up of a randomized placebo-controlled trial. Lancet 2003;361:18691871.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 37.

    Gill HS, Darragh AJ, Cross ML. Optimizing immunity and gut function in the elderly. J Nutr Health Aging 2001;5:8091.

  • 38.

    Isolauri E, Joensuu J, Suomalainen H, et al. Improved immunogenicity of oral D × RRv reassortant rotavirus vaccine by Lactobacillus casei GG. Vaccine 1995;13:310312.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 39.

    Reid G, Bruce AW. Probiotics to prevent urinary tract infections: the rationale and evidence. World J Urol 2006;24:2832.

  • 40.

    Ohashi Y, Nakai S, Tsukamoto T, et al. Habitual intake of lactic acid bacteria and risk reduction of bladder cancer. Urol Int 2002;68:273280.

  • 41.

    Hoppe B, Beck B, Gatter N, et al. Oxalobacter formigenes: a potential tool for the treatment of primary hyperoxaluria type 1. Kidney Int 2006;70:13051311.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 42.

    Bengmark S. Bio-ecological control of acute pancreatitis: the role of enteral nutrition, pro and synbiotics. Curr Opin Clin Nutr Metab Care 2005;8:557561.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 43.

    Olah A, Belagyi T, Issekutz A, et al. Randomized clinical trial of specific lactobacillus and fibre supplement to early enteral nutrition in patients with acute pancreatitis. Br J Surg 2002;89:11031107.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 44.

    Roos K, Holm S. The use of probiotics in head and neck infections. Curr Infect Dis Rep 2002;4:211216.

  • 45.

    Johnston K, Lamport A, Batt RM. An unexpected bacterial flora in the proximal small intestine of normal cats. Vet Rec 1993;132:362363.

  • 46.

    Marshall-Jones ZV, Baillon ML, Croft JM, et al. Effects of Lactobacillus acidophilus DSM13241 as a probiotic in healthy adult cats. Am J Vet Res 2006;67:10051012.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 47.

    Strompfova V, Marcinakova M, Simonova M, et al. Application of potential probiotic Lactobacillus fermentum AD1 strain in healthy dogs. Anaerobe 2006;12:7579.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 48.

    Strompfova V, Laukova A, Ouwehand AC. Lactobacilli and enterococci—potential probiotics for dogs. Folia Microbiol (Praha) 2004;49:203207.

  • 49.

    Manninen TJK, Rinkinen ML, Beasley SS, et al. Alteration of the canine small-intestinal lactic acid bacterium microbiota by feeding of potential probiotics. Appl Environ Microbiol 2006;72:65396543.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 50.

    Rinkinen M, Jalava K, Westermarck E, et al. Interaction between probiotic lactic acid bacteria and canine enteric pathogens: a risk factor for intestinal Enterococcus faecium colonization? Vet Microbiol 2003;92:111119.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 51.

    Weese JS, Anderson RE. Preliminary evaluation of Lactobacillus rhamnosus strain GG, a potential probiotic in dogs. Can Vet J 2002;43:771774.

    • Search Google Scholar
    • Export Citation
  • 52.

    Sauter SN, Benyacoub J, Allenspach K, et al. Effects of probiotic bacteria in dogs with food responsive diarrhoea treated with an elimination diet. J Anim Physiol Anim Nutr (Berl) 2006;90:269277.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 53.

    Nava GM, Bielke LR, Callaway TR, et al. Probiotic alternatives to reduce gastrointestinal infections: the poultry experience. Anim Health Res Rev 2005;6:105118.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 54.

    Lallès JP, Bosi P, Smidt H, et al. Nutritional management of gut health in pigs around weaning. Proc Nutr Soc 2007;66:260268.

  • 55.

    Sargeant JM, Amezcua MR, Waddell L, et al. Pre-harvest interventions to reduce the shedding of E. coli O157 in the faeces of weaned domestic ruminants: a systematic review. Zoonoses Public Health 2007;54:260277.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 56.

    Czarnecki-Maulden GL, Cavadini C, Lawler D. The role of probiotics in GI tract health. St Louis: Nestlé Purina, 2006.

  • 57.

    Vahjen W, Manner K. The effect of a probiotic Enterococcus faecium product in diets of healthy dogs on bacteriological counts of Salmonella spp., Campylobacter spp. and Clostridium spp. in faeces. Arch Tierernahr 2003;57:229233.

    • Search Google Scholar
    • Export Citation
  • 58.

    Bauer E, Williams BA, Smidt H, et al. Influence of the gastrointestinal microbiota on development of the immune system in young animals. Curr Issues Intest Microbiol 2006;7:3551.

    • Search Google Scholar
    • Export Citation
  • 59.

    Liong MT. Probiotics: a critical review of their potential role as antihypertensives, immune modulators, hypocholesterolemics, and perimenopausal treatments. Nutr Rev 2007;68:316328.

    • Search Google Scholar
    • Export Citation
  • 60.

    Madsen IK. Probiotics and the immune response. J Clin Gastroenterol 2006;40:232234.

  • 61.

    Corthésy B, Gaskins HR, Mercenier A. Cross-talk between probiotic bacteria and the host immune system. J Nutr 2007;137 (suppl 2):781S790S.

  • 62.

    Benyacoub J, Czarnecki-Maulden GL, Cavadini C, et al. Supplementation of food with Enterococcus faecium (SF68) stimulates immune functions in young dogs. J Nutr 2003;133:11581162.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 63.

    Ranganathan N, Patel B, Ranganathan P, et al. Probiotic amelioration of azotemia in 5/6th nephrectomized Sprague-Dawley rats. Sci World J 2005;5:652660.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 64.

    Ranganathan N, Patel BG, Ranganathan P, et al. In vitro and in vivo assessment of intraintestinal bacteriotherapy in chronic kidney disease. ASAIO J 2006;52:7079.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 65.

    Palmquist R. A preliminary clinical evaluation of Kibow Biotics®, a probiotic agent, on feline azotemia. J Am Holistic Vet Med Assoc 2006;24:2327.

    • Search Google Scholar
    • Export Citation
  • 66.

    Sahin T, Aydin S, Yuksel O, et al. Effects of the probiotic agent Saccharomyces boulardii on the DNA damage in acute necrotizing pancreatitis induced rats. Hum Exp Toxicol 2007;26:653661.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 67.

    Muftuoglu MA, Isikgor S, Tosun S, et al. Effects of probiotics on the severity of experimental acute pancreatitis. Eur J Clin Nutr 2006;60:464468.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 68.

    Kecskés G, Belágyi T, Oláh A. Early jejunal nutrition with combined pre- and probiotics in acute pancreatitis—prospective, randomized, double-blind investigations [in Hungarian]. Magy Seb 2003;56:38.

    • Search Google Scholar
    • Export Citation
  • 69.

    Mangiante G, Colucci G, Canepari P, et al. Lactobacillus plantarum reduces infection of pancreatic necrosis in experimental acute pancreatitis. Dig Surg 2001;18:4750.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 70.

    van Minnen LP, Timmerman HM, Lutgendorff F, et al. Modification of intestinal flora with multispecies probiotics reduces bacterial translocation and improves clinical course in a rat model of acute pancreatitis. Surgery 2007;141:470480.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 71.

    Xu GF, Lu Z, Gao J, et al. Effect of ecoimmunonutrition supports on maintenance of integrity of intestinal mucosal barrier in severe acute pancreatitis in dogs. Chin Med J (Engl) 2006;119:656661.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 72.

    Qin HL, Su ZD, Gao Q, et al. Early intrajejunal nutrition: bacterial translocation and gut barrier function of severe acute pancreatitis in dogs. Hepatobiliary Pancreat Dis Int 2002;1:150154.

    • Search Google Scholar
    • Export Citation
  • 73.

    Salminen MK, Rautelin H, Tynkkyne S, et al. Lactobacillus bacteremia, clinical significance, and patient outcome, with special focus on probiotic L. rhamnosus GG. Clin Infect Dis 2004;38:6269.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 74.

    Alberda C, Gramlich L, Meddings J, et al. Effects of probiotic therapy in critically ill patients: a randomized, double-blind, placebo-controlled trial. Am J Clin Nutr 2007;85:816823.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 75.

    De Groote MA, Frank DN, Dowell E, et al. Lactobacillus rhamnosus GG bacteremia associated with probiotic use in a child with short gut syndrome. Pediatr Infect Dis J 2005;24:278280.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 76.

    Montalto M, Vastola M, Marigo L, et al. Probiotic treatment increases salivary counts of lactobacilli: a double-blind, randomized, controlled study. Digestion 2004;69:5356.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 77.

    Enache-Angoulvant A, Hennequin C. Invasive Saccharomyces infection: a comprehensive review. Clin Infect Dis 2005;41:15591568.

  • 78.

    Oggioni MR, Pozzi G, Valensin PE, et al. Recurrent septicemia in an immunocompromised patient due to probiotic strains of Bacillus subtilis. J Clin Microbiol 1998;36:325326.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 79.

    Product Review. Probiotic supplements (including Lactobacillus acidophilus, Bifidobacterium, and others). Available at: www.ConsumerLab.com. Accessed Feb 12, 2007.

    • Search Google Scholar
    • Export Citation
  • 80.

    Weese JS. Microbiologic evaluation of commercial probiotics. J Am Vet Med Assoc 2002;220:794797.

  • 81.

    Lata J, Juránková J, Doubek J, et al. Labelling and content evaluation of commercial veterinary probiotics. Acta Vet (Brno) 2006;75:139144.

  • 82.

    Weese JS, Arroyo L. Bacteriological evaluation of dog and cat diets that claim to contain probiotics. Can Vet J 2003;44:212216.

  • 83.

    Biourge V, Vallet C, Levesque A, et al. The use of probiotics in the diet of dogs. J Nutr 2007;128 (suppl 12):2730S2732S.

  • 84.

    Briand V, Buffet P, Genty S, et al. Absence of efficacy of nonviable Lactobacillus acidophilus for the prevention of traveler's diarrhea: a randomized, double-blind, controlled study. Clin Infect Dis 2006;43:11701175.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 85.

    Sanders ME, Hamilton J, Reid G, et al. A nonviable preparation of Lactobacillus acidophilus is not a probiotic (lett). Clin Infect Dis 2007;44:886.

Advertisement