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Featured, Nutrition, Nutrition Notes

Probiotics, Prebiotics, Synbiotics, and Intestinal Health of Dogs and Cats

Probiotics for dogs and cats have become more prevalent. But probiotics, prebiotics, and synbiotics have shown beneficial effects on some GI disorders in various clinical trials.

Jan SuchodolskiDrMedVet, PhD, AGAF, DACVM

Dr. Suchodolski is a professor in small animal medicine, Associate Director for Research, and Head of Microbiome Sciences at the Gastrointestinal Laboratory at Texas A&M University. He received his DrVetMed from the University of Vienna, Austria, and his PhD in veterinary microbiology from Texas A&M University. He is board-certified in immunology by the American College of Veterinary Microbiologists. His research is focused on developing biomarkers for gastrointestinal disease and therapeutic approaches for the modulation of the intestinal microbiota.

Probiotics, Prebiotics, Synbiotics, and Intestinal Health of Dogs and Cats
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Probiotics are defined by the World Health Organization (WHO) as live microorganisms, which when administered in adequate amounts confer a health benefit on the host.¹ Prebiotics are nondigestible food ingredients that are added to diets or used as supplements to modulate the growth or metabolic function of resident intestinal bacteria. Synbiotics are commercially available products that contain both probiotics and prebiotics. This article discusses probiotics for dogs and cats, along with prebiotics and synbiotics and their roles in promoting the intestinal health of dogs and cats.

THE INTESTINAL MICROBIOTA

The gastrointestinal (GI) tract of animals harbors various microorganisms along with their collective genomes.2,3 The estimated total microbial load in the intestine is approximately 100 trillion microbial cells, representing approximately 100 times more microbial genes than the host genome.

Microorganisms within the intestines interact with the host in a mutualistic relationship, providing many metabolic functions.4 Therefore, a balanced intestinal microbiota provides various benefits for host health. Just a few examples are the production of vitamins and other nutrients, immune system modulation, neurodevelopment, gut epithelial health, and protection from enteropathogens.

Shifts in the populations of intestinal bacteria (defined as intestinal dysbiosis) disturb intestinal metabolic and immunologic homeostasis, negatively affecting the host.5 Therefore, treatment strategies aimed at beneficially modulating microbial populations may be of therapeutic benefit.6 Clinical studies reported in the literature have demonstrated that administration of specific probiotic strains can be useful in the prevention and/or treatment of specific intestinal disorders (TABLE 1).

PROBIOTICS, PREBIOTICS, AND SYNBIOTICS FOR DOGS AND CATS

Probiotics

The WHO definition of probiotics stresses that health benefits need to be demonstrated before a strain of bacteria can be designated as a probiotic. In the U.S., the Food and Drug Administration does not regulate probiotics; therefore, no governing agency oversees the label claims of probiotic products. The most commonly used probiotic strains in commercial products are lactic acid–producing bacteria (e.g., Lactobacillus, Enterococcus, Streptococcus, and Bifidobacterium species), which have traditionally been associated with health benefits. However, clinical studies have also demonstrated health benefits from other microorganisms, including specific strains of Escherichia coli13 and yeasts (e.g., Saccharomyces boulardii),7,14 which are also commercially available as probiotics.

Mechanisms of Action

The health effects of probiotics are strain-specific; every probiotic strain may have unique functional and immunologic characteristics and, therefore, potentially a different mechanism of action. To select a probiotic product for clinical use, it is crucial to know its mechanisms, which probiotic strains it contains, and whether there is scientific evidence that these particular strains have shown beneficial effects for the targeted disorder (e.g., acute diarrhea, chronic enteropathy).7-10,15

A common indication for probiotic use is modulation of the intestinal microbiota. However, recent studies have shown that because the amount of probiotic bacteria given is very small compared to the number of resident intestinal bacteria, probiotics do not induce major changes in intestinal microbiota.16

The specific mechanisms of action of probiotic strains remain poorly defined, especially in clinical settings. Because most studies have evaluated mechanisms of action in vitro, a direct comparison cannot be made to clinical settings; however, studies can suggest potential clinical benefit. For example, some probiotic strains are immunomodulatory and stimulate the release of anti-inflammatory cytokines or enhance production of immunoglobulin A.17 Other strains may improve intestinal mucosal barrier function and reduce “leaky gut.”10 Some strains may also reduce growth of enteropathogens because of their secretion of antimicrobial peptides.18

Considerations for Use

The most promising applications for probiotics are treatment of acute uncomplicated diarrhea, prevention of stress diarrhea, prevention of antibiotic-associated GI signs, and adjunct therapy for chronic enteropathies (TABLE 1). Probiotics need 1 to 3 days to colonize the intestines.19 When the goal is prevention of stress-related diarrhea (during periods of weaning, boarding, or traveling or for working dogs), prophylactic administration of a probiotic a few days to weeks ahead of the event may increase success. Similarly, if the goal is prevention of antibiotic-associated GI signs, administering probiotics a few days ahead of a procedure will increase success.

Probiotics, like any other bacteria, can be either susceptible or resistant to concurrently administered antibiotics. For the prevention of antibiotic-associated GI signs, antibiotics and probiotics should be prescribed concurrently. It is worthwhile to contact the manufacturer to obtain information about the susceptibility patterns of their products. If this information is not available, probiotics and antibiotics should be administered at least 4 hours apart to avoid inactivation of the probiotic. A useful property of yeast probiotics is their natural resistance to antibiotics; therefore, administration of yeast does not promote antimicrobial resistance and can be administered at the same time as antibiotics.

For proper immune stimulation, long-term administration over weeks to months is probably preferable.17 Long-term administration over several months is also recommended for dogs and cats with chronic enteropathy in order to elicit optimal benefits for intestinal barrier function and immune regulation.10,11,20 Because probiotics will be eliminated after administration ends, their health benefits will also end at that time.19

Prebiotics

Prebiotics are nondigestible food ingredients that beneficially affect the host by selectively stimulating the growth and/or activity of one or a limited number of bacterial species already resident in the colon.21 They are primarily dietary fiber sources, such as fructooligosaccharides, pectins, inulins, resistant starches, β-glucans, and various others.22

As with probiotics, the desired outcome after giving prebiotics is improvement of host health.21 However, the specific aim of giving prebiotics is to promote growth and function of the beneficial bacteria already present in the gut. Intake of prebiotics can significantly modulate the colonic microbiota by increasing the number of specific bacteria and thus changing the composition of the microbiota.23 Prebiotics are metabolized by the resident microbiota of the colon, which, depending on fermentability, will result in the production of the short-chain fatty acids butyrate, propionate, and acetate.23 These metabolites will diffuse through gut enterocytes and provide either local effects (e.g., enhance the intestinal epithelial barrier, decrease pro-inflammatory cytokines, regulate intestinal motility) or systemic effects (e.g., provide energy for the host).24,25 Apart from direct prebiotic effects, dietary fibers can have additional functions in the GI tract. Psyllium, for example, has water-binding and bile acid–binding properties that improve fecal consistency, increase the intestinal mucus layer, and have beneficial effects on cell proliferation in the intestinal tract.26

Synbiotics

Some resident bacteria that thrive on prebiotics might not have the same health benefits as exogenous probiotics. Administering probiotics and prebiotics together may enhance the potential for eliciting health benefits, and some commercially available products contain both probiotics and prebiotics. These combinations are called synbiotics.

SAFETY AND QUALITY

Safety

Probiotics and prebiotics are generally safe for dogs and cats. The most common side effects of prebiotics are flatulence and abdominal discomfort due to increased intestinal gas production. After receiving probiotics or prebiotics, some animals may experience constipation or loose stools, which may resolve after dose adjustment. Similarly, some animals may initially experience flatulence and/or looser stools for the first few days, especially when given high-dose multistrain probiotics. In such cases, reducing the dose for the first few days is often sufficient to ameliorate these clinical signs, after which the dose can be increased back to full.

Serious side effects are very rarely reported. A limited number of case reports have shown that probiotics can potentially translocate and cause septicemia in hospitalized human patients,27 but less is known about their effects in veterinary patients. The author recommends that probiotics be used with caution in immunocompromised patients. However, clinical studies have shown that probiotics can be used in dogs with parvovirosis28 and acute hemorrhagic diarrhea.9

Quality

A major concern when using commercially available probiotics is the product quality and its stability during shipping and storage. To confer a health benefit, probiotics need to be administered in certain amounts; because these amounts were ideally demonstrated in clinical studies in the target species, high-quality formulations are crucial. Unfortunately, several studies have shown that many probiotic products marketed for veterinary use lack proper quality standards.29,30 Most commercial product labels do not provide sufficient information about the probiotic strain and amount, and many also state incorrect scientific names and/or incorrectly spelled names of the bacteria, indicating potential poor quality control and making it difficult to choose the appropriate product for clinical use. In addition, several products contained fewer probiotic organisms than were listed on the label.29,30 Therefore, the author recommends using probiotic formulations produced by reputable manufacturers and that have demonstrated a benefit in clinical studies (TABLE 1).

TAKE-HOME POINTS

  • Probiotics are live microorganisms, prebiotics are nondigestible food ingredients that support resident intestinal bacteria, and synbiotics are a combination of both.
  • When selecting a probiotic product for clinical use, know its mechanisms, which strains it contains, and whether it has been evaluated for the targeted disorder.
  • No governing agency oversees the label claims on probiotics. Products are most likely to be of good quality if they were produced by a reputable manufacturer and underwent clinical study.
  • The most promising applications for probiotics are treatment of acute uncomplicated diarrhea, prevention of stress diarrhea, prevention of antibiotic-associated GI signs, and adjunct therapy for chronic enteropathies.
  • Probiotics are generally safe but should be used with caution in immunocompromised patients.
References

1. Food and Agriculture Organization of the United Nations/World Health Organization. Guidelines for the Evaluation of Probiotics in Food. who.int/foodsafety/fs_management/en/probiotic_guidelines.pdf. Accessed May 2020.

2. Shreiner AB, Kao JY, Young VB. The gut microbiome in health and in disease. Curr Opin Gastroenterol 2015;31(1):69-75.

3. Turnbaugh PJ, Ley RE, Hamady M, et al. The human microbiome project. Nature 2007;449:804-810.

4. Pilla R, Suchodolski JS. The role of the canine gut microbiome and metabolome in health and gastrointestinal disease. Front Vet Sci 2020;6:498.

5. Suchodolski JS. Diagnosis and interpretation of intestinal dysbiosis in dogs and cats. Vet J 2016;215:30-7.

6. Suchodolski JS, Jergens AE. Recent advances and understanding of using probiotic-based interventions to restore homeostasis of the microbiome for the prevention/therapy of bacterial diseases.
Microbiol Spectr 2016;4(2).

7. D’Angelo S, Fracassi F, Bresciani F, et al. Effect of Saccharomyces boulardii in dog with chronic enteropathies: double-blinded, placebo-controlled study. Vet Rec 2018;182(9):258.

8. 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 Intern Med 2011;25(4):856-860.

9. Ziese AL, Suchodolski JS, Hartmann K, et al. Effect of probiotic treatment on the clinical course, intestinal microbiome, and toxigenic Clostridium perfringens in dogs with acute hemorrhagic diarrhea.
PLoS One 2018;13(9):e0204691.

10. White R, Atherly T, Guard B, et al. Randomized, controlled trial evaluating the effect of multi-strain probiotic on the mucosal microbiota in canine idiopathic inflammatory bowel disease. Gut Microbes 2017;8(5):451-466.

11. Hart ML, Suchodolski JS, Steiner JM, Webb CB. Open-label trial of a multi-strain synbiotic in cats with chronic diarrhea. J Fel Med Surg 2012;14(4):240-245.

12. Stokes JE, Price JM, Whittemore JC. Randomized, controlled, crossover trial of prevention of clindamycin-induced gastrointestinal signs using a synbiotic in healthy research cats. J Vet Intern Med 2017;31(5):1406-1413.

13. Zyrek AA, Cichon C, Helms S, et al. Molecular mechanisms underlying the probiotic effects of Escherichia coli Nissle 1917 involve ZO-2 and PKCzeta redistribution resulting in tight junction and epithelial barrier repair. Cell Microbiol 2007;9(3):804-816.

14. Aktas MS, Ozkanlar Y. Efficacy of Saccharomyces boulardii as a probiotic in dogs with lincomycin induced diarrhoea. Bull Vet Inst Pulawy 2007;51(3):365-369.

15. Nixon SL, Rose L, Muller AT. Efficacy of an orally administered anti-diarrheal probiotic paste (Pro-Kolin Advanced) in dogs with acute diarrhea: a randomized, placebo-controlled, double-blinded clinical study. J Vet Intern Med 2019;33(3):1286-1294.

16. Pilla R, Guard BC, Steiner JM, et al. Administration of a synbiotic containing Enterococcus faecium does not significantly alter fecal microbiota richness or diversity in dogs with and without food-responsive chronic enteropathy. Front Vet Sci 2019;6:277.

17. 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(4):1158-1162.

18. Schmitz S, Suchodolski J. Understanding the canine intestinal microbiota and its modification by pro-, pre- and synbiotics – what is the evidence? Vet Med Sci 2016;2(2):71-94.

19. Garcia-Mazcorro JF, Lanerie DJ, Dowd SE, et al. Effect of a multi-species synbiotic formulation on fecal bacterial microbiota of healthy cats and dogs as evaluated by pyrosequencing. FEMS Microbiol Ecol 2011;78(3):542-554.

20. Rossi G, Pengo G, Caldin M, et al. Comparison of microbiological, histological, and immunomodulatory parameters in response to treatment with either combination therapy with prednisone and metronidazole or probiotic VSL#3 strains in dogs with idiopathic inflammatory bowel disease. PLoS One 2014;9(4):e94699.

21. Gibson GR, Roberfroid MB. Dietary modulation of the human colonic microbiota: introducing the concepts of prebiotics. J Nutr 1995;125(6):1401-1412.

22. Gibson GR, Scott KP, Rastall RA, et al. Dietary prebiotics: current status and new definition. Food Sci Technol Bull Funct Foods 2010;7(1):1-19.

23. Hussein HS, Flickinger EA, Fahey GC, Jr. Petfood applications of inulin and oligofructose. J Nutr 1999;129(7 Suppl):1454S-1456S.

24. Barry KA, Middelbos IS, Vester Boler BM, et al. Effects of dietary fiber on the feline gastrointestinal metagenome. J Proteome Res 2012;11(12):5924-5933.

25. Swanson KS, Grieshop CM, Flickinger EA, et al. Supplemental fructooligosaccharides and mannanoligosaccharides influence immune function, ileal and total tract nutrient digestibilities, microbial populations and concentrations of protein catabolites in the large bowel of dogs. J Nutr 2002;132(5):980-989.

26. Barry KA, Wojcicki BJ, Middelbos IS, et al. Dietary cellulose, fructooligosaccharides, and pectin modify fecal protein catabolites and microbial populations in adult cats. J Anim Sci
2010;88(9):2978-2987.

27. Land MH, Rouster-Stevens K, Woods CR, et al. Lactobacillus sepsis associated with probiotic therapy. Pediatrics 2005;115(1):178-181.

28. Arslan HH, Saripinar Aksu D, Terzi G, Nisbet C. Therapeutic effects of probiotic bacteria in parvoviral enteritis in dogs. Revue Méd Vét 2012;163(2):55-59.

29. Weese JS, Martin H. Assessment of commercial probiotic bacterial contents and label accuracy. Can Vet J 2011;52(1):43-46.

30. Weese JS. Microbiologic evaluation of commercial probiotics. JAVMA 2002;220(6):794-797.

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