What do all those ‘biotics’ do? Turns out, a lot

We hear a lot about gut health and the gut microbiome these days. As veterinarians, we know there are many brands of probiotic and prebiotic supplements available claiming to bring “good” and “bad” gut bacteria into a healthier balance, help relieve gastrointestinal (GI) conditions, boost immunity, and even benefit heart and brain health.

As experts in the veterinary field explore the gut microbiome and how it affects the GI system—as well as its impact on other body systems—they have learned that microbiome health may play a key role in the overall health of pets.

Now, how do veterinarians know if a probiotic, prebiotic, synbiotic, or postbiotic—the newest “biotic” coming on the scene—is safe and effective? What exactly do all of these biotics do, anyway? Let’s look at the microbiome, and then at the roles each of the biotics can play in GI health.

A glimpse into the gut

The gut is home to trillions of microrganisms, and the GI microbiome is the dynamic environment in which these microorganisms—also known as microbiota—exist. It is not just the microbiota themselves that are part of the microbiome: it is also their genetic material and the way that genetic material interacts with the GI environment.

The GI microbiome comprises a complex ecosystem where the microbiota and host work together to establish and maintain a functional barrier protecting the host from infection by pathogens. The microbiome also plays an integral role in many physiological functions, including energy balance, metabolism, and immune health.

From a companion animal perspective, we now recognize there are changes to the GI microbiome that can trigger clinical signs in dogs and cats that may contribute to disease. When we think about the importance of microbiome health in our patients, we should consider ways we can help modulate the microbiome to help manage disease processes.

Bacterial imbalance:A punch to the gut

Many factors can trigger negative changes in the microbiome during an animal’s life span, including infectious diseases, diet changes, and chronic disease states. Perhaps one of the biggest insults to the microbiome is caused by administering antibiotics. For example, metronidazole can disrupt the GI microbiome for days, weeks, or even longer.¹

Tylosin has also been shown to cause dysbiosis—defined as an imbalance between beneficial and potentially pathogenic microorganisms—even in healthy dogs.² Fortunately, the move toward antibiotic stewardship has many clinicians striving to use antibiotics only when necessary and appropriate. Meanwhile, when an antibiotic is necessary, administering a probiotic along with it can help blunt negative GI effects.

In one study of shelter dogs with diarrhea, the addition of probiotic Enterococcus faecium SF68 with metronidazole appeared to enhance clinical responses compared to metronidazole alone.³ Another study revealed E. faecium SF68 lessened the severity of clinical signs associated with administrating amoxicillin-clavulanate in cats.⁴

The role of dietary supplements

Diet has a profound effect on the health of the GI microbiome, and nutritional interventions with prebiotics, probiotics, synbiotics, and postbiotics offer veterinarians opportunities to positively affect microbiome health. Additionally, it is important for veterinarians and clients to know the nutritional supplements administered to pets are safe and effective.

The International Scientific Association for Probiotics and Prebiotics (ISAPP)—a nonprofit organization committed to advancing the science of probiotics and prebiotics—has published expert consensus documents on the definitions of probiotics, prebiotics, synbiotics, and postbiotics, as well as materials that explain their scope.

Here is a brief look at how ISAPP defines the different biotics and what they do:

• Probiotic. A live microorganisms that, when administered in adequate amounts, confers a health benefit on the host.⁵Probiotics can help the immune system function properly, aid digestion by breaking down food, keep pathogenic microorganisms in check, and facilitate nutrient absorption, among other benefits.⁶As probiotics contain live microorganisms, reputable manufacturers take steps to ensure their stability and survival during production, storage, transport and shelf life. Veterinarians should recommend a probiotic that includes an expiration date, the strain(s) of probiotic used, and guaranteed levels of live microorganisms contained in the product. If a product does not contain this information, its efficacy cannot be assured.
• Prebiotic. A substrate selectively utilized by host microorganisms, conferring a health benefit.⁷Most prebiotics are dietary fibers, but not all dietary fibers are prebiotics.⁸ Prebiotics provide health benefits by specifically altering either the composition or function of the gut microbiota.⁸ They can also potentially improve mineral absorption and aid in regulating satiety.⁸ One caution with prebiotic use is that too much fiber in a diet can sometimes produce excess fermentation in the gut, resulting in GI signs, including gas and bloating. As a result, care should be taken to provide accurate dosing.
• Synbiotic. A mixture comprising live microorganisms and substrate(s) selectively utilized by host microorganisms that confers a health benefit on the host.⁹Synbiotics can be formulated using two approaches¹⁰:

  1) A complementary synbiotic, which is a mixture of probiotic(s) and prebiotics(s). Each works independently to achieve one or more health benefits.
  2) A synergistic synbiotic, which is a combination of a selectively utilized substrate and a live microbe chosen for its ability to deliver a health effect. Components in synergistic synbiotics work together to bring about resulting health benefit(s).

• Postbiotic. A preparation of inanimate microorganisms and/or their components that confers a health benefit on the host.¹¹According to ISAPP, a postbiotic is something that was alive but is now in its “after life” phase and is inanimate.¹² Postbiotics are rendered unviable by applying processes to live microbes, such as heat, radiation, high pressure or lysis.¹² Unlike probiotics, the efficacy of postbiotics does not rely on the survival of live microorganisms throughout the manufacturing process; as a result, they are better able to sustain production, transport, and storage conditions.^13,14Postbiotics are only recently making an appearance in the veterinary field and are typically found in the form of supplements. To date, published research on postbiotics for companion animals is focused on their effects in healthy animals (See: “Gut check”).
  

  Gut check Observations in healthy pets include the following, depending on the specific postbiotic being evaluated: Increased fecal IgA in dogs and cats, indicating an active gut immune system15 Reductions of inflammatory cytokines in dogs 24 hours post-exercise (e.g. IL-8 and IL-18)15 Improved response to mild, naturally occurring stress in dogs and cats15 Increased microbiome diversity and resilience in dogs and cats15 Improved stool quality in dogs exposed to mild transport stress16 Increased antioxidant capacity in dogs16

  Importantly, postbiotics may provide opportunities in the future to reduce, or even replace, antibiotics in certain situations. As mentioned above, antibiotics alter gut microbial diversity and population, with some effects being brief and others long-lasting.¹⁷ Antibiotic-induced dysbiosis may induce metabolic and immunological disorders.¹⁷ Conversely, postbiotics may offer comparable benefits without the adverse effects of antibiotic medications while offering clear advantages.¹⁷ While it is too early to say postbiotics can replace antibiotics like prebiotics and probiotics may do in certain situations, continued scientific study will delineate probiotics’ efficacy more fully.

The safety of veterinary supplements

As we begin to see supplements become more popular and incorporated into foods, clinicians should look at studies examining their safety, as well as their efficacy. Just as with any supplement or diet, it is important to recommend those that have been proven through scientific studies to be safe and effective.

The National Animal Supplement Council (NASC) is a nonprofit trade association that works to protect and enhance the animal health supplement industry. The organization’s Quality Program offers a quality seal manufacturers can place on their packaging that ensures a supplement has met certain criteria. To display the NASC Quality Seal, NASC members must pass a third-party quality audit every two years, maintain ongoing compliance with NASC quality standards, participate in annual continuing education and pass random independent testing of their products. This quality seal should be an important element for clinicians to consider when determining which GI supplements to recommend for their patients.

Since GI health plays such an important part in the overall well-being of pets, having easy-to-administer tools such as GI-friendly diets and biotics can help get—and keep—dogs and cats healthier.

For clinicians, it is important to recommend scientifically proven products for the management of GI health. For researchers, there is ongoing opportunity to discover new and better options for eventual clinical use in the burgeoning field of biotics.

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Martha Cline, DVM, DACVIM (Nutrition), is a board-certified veterinary nutritionist and senior manager for Veterinary Technical Communications for Nestlé Purina PetCare. Dr. Cline sees nutrition patients on a part-time basis at Red Bank Veterinary Hospitals (Tinton Falls, New Jersey). She served as chair of the 2021 American Animal Hospital Association (AAHA) Nutrition and Weight Management Guidelines Task Force.

References

1. Pilla R, Gaschen FP, Barr JW, et al. Effects of metronidazole on the fecal microbiome and metabolome in healthy dogs. J Vet Intern Med 2020 Sep;34(5):1853-1866. Epub 2020 Aug 28. PMID: 32856349; PMCID: PMC7517498.
2. Manchester AC, Webb CB, Blake AB, et al. Long-term impact of tylosin on fecal microbiota and fecal bile acids of healthy dogs. J Vet Intern Med. 2019 Nov;33(6):2605-2617. Epub 2019 Oct 31. PMID: 31674054; PMCID: PMC6872867.
3. Fenimore A., Martin L, Lappin M. (2017). Evaluation of metronidazole with and without Enterococcus faecium SF68 in shelter dogs with diarrhea. Topics in Companion Animal Medicine, 32, 100-103.
4. Torres-Henderson C, Summers S, Suchodolski J, et al. (2017). Effect of Enterococcus faecium strain SF68 on gastrointestinal signs and fecal microbiome in cats administered amoxicillin-clavulanate. Topics in Companion Animal Medicine, 32(3), 104-108.
5. Hill C, Guarner F, Reid G, et al. (2014). Expert consensus document: The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nature Reviews Gastroenterology & Hepatology, 11(8), 506-514.
6. International Scientific Association for Probiotics and Prebiotics (ISAPP) “Probiotics” infographic. 2019, International Scientific Association for Probiotics and Prebiotics. Accessed May 24, 2024.
7. Gibson GR, Hutkins R, Sanders ME, et al. Expert consensus document: The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of prebiotics. Nature Reviews Gastroenterology & Hepatology, 14(8), 491-502.
8. International Scientific Association for Probiotics and Prebiotics (ISAPP) “Prebiotics” infographic. 2019, International Scientific Association for Probiotics and Prebiotics. Accessed May 24, 2024.
9. Swanson KS, Gibson GR, Hutkins R, et al. (2020) The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of synbiotics. Nature Reviews Gastroenterology & Hepatology. 17(11), 687-701.
10. International Scientific Association for Probiotics and Prebiotics (ISAPP) “Synbiotics” infographic. 2021, International Scientific Association for Probiotics and Prebiotics. Accessed May 24, 2024.
11. Salminen S, Collado MC, Endo A, et al. (2021). The International Scientific Association of Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of postbiotics. Nature Reviews Gastroenterology & Hepatology, 18(9), 649-667.
12. Vinderola G, Sanders ME, Cunningham M, et al. (2024). Frequently asked questions about the ISAPP postbiotic definition. Frontiers in Microbiology, 14, 1324565.
13. Wegh CAM, Geerlings SY, Knol J, et al. (2019). Postbiotics and their potential applications in early life nutrition and beyond. International Journal of Molecular Sciences, 20(19).
14. Mosca A, Abreu YAAT, Gwee KA, et al. (2022). The clinical evidence for postbiotics as microbial therapeutics. Gut Microbes, 14(1), 2117508.
15. Spears JK, Czarnecki-Maulden G, Ameho, C, et al. (2016). Beyond probiotics: Heat-treated probiotics in companion animal health. Companion Animal Nutrition Summit: Pet Nutrition: Beyond Essential, Fort Lauderdale, FL.
16. Koziol SA, Oba PM, Soto-Diaz K, et al. (2023). Effects of a Lactobacillus fermentation product on the fecal characteristics, fecal microbial populations, immune function, and stress markers of adult dogs. Journal of Animal Science, 101.
17. Puccetti M, Xiroudaki S, Ricci M, et al. (2020). Postbiotic-enabled targeting of the host-microbiota-pathogen interface: Hints of antibiotic decline? Pharmaceutics, 12(7).