It has been said that there are 10 times as many bacterial cells as human cells in the average human body.1 It has been said, but it’s probably not true.2 Still, there is undoubtedly a large and complex ecology of microorganisms living in and on every individual mammal, and this ecology has multifaceted and important health effects.3 Microorganisms produce important nutrients, influence immune function and digestion, and have other beneficial effects on health.3 Disruption of this ecosystem can have negative health effects, as anyone who has suffered from antibiotic-associated diarrhea can attest! Our growing understanding of the importance of commensal microorganisms has led to the hope that one day we may be able to deliberately alter the microbial flora of healthy animals as well as veterinary patients in an effort to achieve health effects that are targeted and beneficial. Microorganisms, such as bacteria or yeast, that are administered to prevent or treat disease are known as probiotics, and a very lucrative industry has since emerged to produce and sell these particular organisms. However, despite well-established basic science showing the importance of the microbial flora to health, it is not a simple matter to produce safe and effective probiotic therapies. Any effective probiotic must be able to survive ingestion and establish itself in the body, and then influence an enormous, complex, and poorly understood microbial ecology in a positive way. One skeptic has likened giving probiotics to planting a putting green in the Amazon rainforest. Inserting a small quantity of a non-native organism into such an ecosystem may very well have little impact. The devil is in the details, and much remains to be learned about probiotic organisms, formulation and dosing, species and individual differences, and other critical factors involved in clinical use of probiotic treatments. That said, the problem of poor quality control in unregulated supplements also pertains to probiotics. Studies have shown that the majority of veterinary probiotics sampled are mislabeled or do not contain the type and amount of microorganism they are supposed to contain.4-5 Even if particular organisms are useful for specific indications, it cannot be assumed that other probiotic products will be effective or in the same circumstances or that effects seen in clinical studies will then translate across species or indications. Veterinary probiotic research Probiotics have often been recommended for a variety of clinical problems in veterinary species, including spontaneous and antibiotic-associated diarrhea, inflammatory bowel disease, viral upper respiratory infection, and renal failure. A handful of studies have been done looking at these and other uses, mostly looking at indications for which there is some positive evidence in humans.6-7 Some proponents also have suggested probiotics may have improve or protect health individuals without identifiable disease, but there is no reliable human or veterinary research evidence to support this.6 Below are some common indications for which probiotics have been recommended and brief summaries of the available evidence. Acute diarrhea Several studies show beneficial effects on probiotics on prevention and treatment of acute diarrhea in dogs and cats.6-9 These studies are small, employ a variety of probiotics and study populations, and have some methodological limitations. There are also studies that have failed to find significant effects of probiotics for diarrhea in these species.6,10 Similarly, the limited research in horses is also mixed, with studies finding benefits, no effect, and even potential increases in diarrhea with use of probiotics.11-12 These studies also vary in the probiotic used, patient population, and methods. Overall, the existing evidence for the value of probiotics in preventing and treating acute diarrhea is encouraging, though still not robust. Chronic GI disease Other studies show effects of probiotics on the GI flora and the host in dogs with food-responsive enteropathy, idiopathic inflammatory bowel disease, and other chronic enteropathies.6 However, no definitive studies show improvement in long-term symptom control or other clinically important outcomes on dogs or cats with chronic GI disease. Atopic dermatitis Given that probiotics have various effects on the immune system, several studies have looked at the potential value of probiotic treatment in management of allergic dermatopathy.6,13-14 Once again, there are some encouraging results, however predictable, durable, clinically meaningful improvement in real-world use has not yet been shown. Upper respiratory infections A single pilot study has been reported evaluating probiotic use in cats with feline herpesvirus infection.15 The study was small, and results were mixed and did not show a convincing beneficial effect. As with atopic dermatitis, additional research is warranted, but there isn’t much basis for clinical use at this point. Chronic kidney disease Some preliminary studies in rats and pigs have suggested probiotics might reduce azotemia or otherwise benefit patients with chronic kidney disease.16 Uncontrolled observations in cats and dogs also have suggested some such effects, though the risk of bias in such studies is very high.16 At least one commercial probiotica has been marketed for this purpose and has been the subject of several studies.16-18 Though small and with typical limitations, these controlled studies have not found any convincing evidence of a meaningful impact of this probiotic on renal disease in dogs or cats. Safety of probiotics Whenever there is limited research evidence, it is impossible to be certain of not only the efficacy but also the safety of medical therapies. Both actual and theoretical risks from probiotics have been discussed in the human medical literature.19-20 Generally, probiotics are considered safe in immunocompetent humans, though not all the potential risks are well characterized.19-20 Some evidence of direct patient harm has been reported in veterinary species.11 There also are concerns about indirect risks, such as the transmission of antibiotic resistance genes from probiotic species to pathogenic organism. This led to the refusal of one regulatory agency, the European Food Safety Authority, to approve the use of a commercial veterinary probiotic when the constituent organism was found to be resistant to clindamycin.21 Despite such concerns and the uncertainty of limited evidence, probiotics have been widely available and frequently used, in research and clinical settings, without many reports of obvious harm to veterinary patients. PROBIOTIC TAKEAWAYS Strong pre-clinical evidence, from in vitro and lab animal studies, suggest probiotics could have significant beneficial effects. There is moderate to strong evidence in humans for some probiotics for some indications, such as antibiotic-associated diarrhea and irritable bowel syndrome. For most indications, however, the evidence is encouraging but still weak. In veterinary patients, the best case can be made for use of probiotics in acute diarrhea, though even for this indication the evidence is neither strong nor consistent. The evidence for most other indications is insufficient to draw any reliable conclusions. Despite a lack of research specifically assessing safety, probiotics generally are considered safe in individuals that are considered immunocompetent. Many veterinary probiotic products are inaccurately labeled, and there is poor quality control in the probiotic market. References Sender R, Fuchs S, Milo R. Are We Really Vastly Outnumbered? Revisiting the Ratio of Bacterial to Host Cells in Humans. Cell. 2016;164:337–40. Sender R, Fuchs S, Milo R. Revised Estimates for the Number of Human and Bacteria Cells in the Body. PLoS Biol. 2016;14(8):e1002533. Zhang Y-J, Li S, Gan R-Y, et al. Impacts of Gut Bacteria on Human Health and Diseases. Sugumaran M, ed. Int J Mol Sci. 2015;16(4):7493-7519. Weese JS. Microbiologic evaluation of commercial probiotics. JAVMA. 2002;220(6): 794-7. Weese JS, Martin H. Assessment of commercial probiotic bacterial contents and label accuracy. Canadian Vet J. 2011;52:43–6. Jugan MC, Rudinsky AJ, Parker VJ, Gilor C. Use of probiotics in small animal veterinary medicine. JAVMA. 2017;250(5):519-28. Wynn SG. Probiotics in veterinary practice. JAVMA. 2009;234(5):606-13. Herstad HK, Nesheim BB, L’Abée-Lund T, et al. Effects of a probiotic intervention in acute canine gastroenteritis–a controlled clinical trial. J Small Anim Pract. 2010;51(1):34-8. Kelley RL, Minikhiem D, Kiely B, et al. Clinical benefits of probiotic canine-derived Bifidobacterium animalis strain AHC7 in dogs with acute idiopathic diarrhea. Vet Therapeutics. 2009;10(3):121-30. Bybee SN, Scorza AV, Lappin MR. Effect of the Probiotic Enterococcus faecium SF68 on Presence of Diarrhea in Cats and Dogs Housed in an Animal Shelter. J Vet Int Med. 2011;25(4):856-60. Weese JS, Rousseau J, Evaluation of Lacotbacilluc pentosus WE7 for prevention of diarrhea in neonatal foals. JAVMA. 2005;226(12):2031-34. Schoster A, Weese JS, Guardabassi L. Probiotic Use in Horses – What is the Evidence for Their Clinical Efficacy? J Vet Intern Med. 2014;28:1640–52. Kim H, Rther IA, Kim H, et al. A Double-Blind, Placebo Controlled-Trial of a Probiotic Strain Lactobacillus sakei Probio-65 for the Prevention of Canine Atopic Dermatitis. J Microbiol Biotechnol. 2015; 25(11): 1966-69. Ohshima-Terada Y, Higuchi Y, Kumagai T, et al. Complementary effect of oral administration of Lactobacillus paracasei K71 on canine atopic dermatitis. Vet Dermatol. 2015;26(5):350-3. Lappin MR, Veir JK, Satyaraj E, et al. Pilot study to evaluate the effect of oral supplementation of Enterococcus faecium SF68 on cats with latent feline herpesvirus 1. J Fel Med Surg. 2009;11(8):650-4. Polzin DJ. Probiotic Therapy of Chronic Kidney Disease. ACVIM Forum 2011. Denver, CO. Kanakubo S, Ross H, Finke J. Influence of AzodylTM on Urea and Water Metabolism in Uremic Dogs. ACVIM Forum 2013 Seattle, WA. Rishniw M, Wynn S. Azodyl fails to reduce azotemia in cats with chronic kidney Disease (CKD) when sprinkled onto food. J Feline Med Surg. 2011;Jun;13(6):405-9. Didari T, Solki S, Mozaffari S, et al. A systematic review of the safety of probiotics. Expert Opin Drug Saf. 2014;13(2):227-39. Hempel S, Newberry S, Ruelaz A, et al. Safety of probiotics used to reduce risk and prevent or treat disease. Evid Rep Technol Assess (Full Rep). 2011;(200):1-645. EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP); Scientific Opinion on the safety and efficacy of Prostora Max (Bifidobacterium animalis) as a feed additive for dogs. EFSA Journal. 2012;10(12):2964 . Dr. McKenzie discovered evidence-based veterinary medicine after attending the University of Pennsylvania School of Veterinary Medicine and working as a small animal general practice veterinarian. He has served as president of the Evidence-Based Veterinary Medicine Association and reaches out to the public through his SkeptVet blog, the Science-Based Medicine blog, and more. He is certified in medical acupuncture for veterinarians. Columnists’ opinions do not necessarily reflect those of Veterinary Practice News.
