There is extensive research on probiotic supplementation, and how probiotics can positively impact the intestinal microbiome in small animals.

In Part 1 of this series (IVC Journal, Spring 2018), we looked at the discovery of probiotics along with research documenting the importance of a balanced intestinal microbiome. We discovered how many modern medical practices can disturb the balance of gut bacteria in an unhealthy way, and the role probiotics play in mitigating dysbiosis and maintaining intestinal lining integrity. In Part 2, we will explore more detailed research on the health benefits of probiotics.

Probiotic effects on healthy pets

Probiotic supplementation can have beneficial effects on healthy animals. In one study, dogs were given probiotics for seven days. Even though the administered strains disappeared within a week after discontinuation, there was a sustained change in the population of indigenous lactic acid–producing bacteria in jejunal contents, with native L. acidophilus strains predominating.¹ In another study where dogs were supplemented with L. acidophilus, an associated increase in the numbers of fecal lactobacilli, along with a decrease in clostridial organisms, was observed. Furthermore, there were significant increases in RBCs, HCT, hemoglobin concentration, neutrophils, monocytes and serum IgG,  and reductions in RBC fragility and serum NO²Supplementation of puppies with Lactobacillus caused an increase in appetite and food intake, which led to higher daily weight gain.³

When 15 healthy cats were supplemented with L. acidophilus, populations of fecal bifidobacteria, Clostridium spp and Enterococcus faecalis, decreased. Granulocyte phagocytic activity and eosinophil numbers increased, while erythrocyte fragility and plasma endotoxin concentrations decreased.⁴ Other researchers found that “Feeding studies with a Lactobacillus acidophilus probiotic have shown positive effects on carriage of Clostridium spp. in canines and on recovery from Campylobacter spp. infection in felines. Immune function was improved in both species.”^5]

Probiotics and GI disease

Studies show that chronic GI issues, such as inflammatory bowel disease (IBD), are associated with alterations in the microbiome. There are consistent decreases in Firmicutes and Bacteroidetes and increases in Proteobacteria species. These changes lead to susceptibilities in the innate immune system of dogs and cats with IBD.⁶ Other research confirms there is a predictable pattern of dysbiosis in dogs with various GI diseases, and that the bacterial groups commonly decreased are those considered to be important short-chain fatty acid producers.⁷ This is important because short-chain fatty acids are needed to maintain the health of enterocytes.

Probiotics and the immune system

The gut associated lymphoid tissue (GALT) makes up 70% to 80% of the body’s immune system. This means the GI tract is the largest organ of the immune system. Multiple studies show that probiotic supplementation can affect the systemic immune system in many ways. When puppies were given the probiotic E. faecium SF68 from weaning to one year of age, their serum IgA concentrations were higher, they had a greater proportion of mature B cells, and they had higher titers after distemper vaccination than control puppies.⁸ Also, several studies in humans show that probiotics can prevent and/or treat food and atopic allergies.⁹,¹⁰ A study in dogs found that when puppies were given a probiotic supplement before the age of six months, they had decreased allergen-specific IgE and reduced development of atopic dermatitis in the first six months. A three-year follow-up with an allergen challenge demonstrated a low IL-10 for all allergens in probiotics-exposed dogs.¹¹ Other researchers concluded: “Many studies have found that gut microbes are involved in the immunopathogenesis of Diabetes Mellitus. Probiotics strengthen the host’s intestinal barrier and modulate the immune system….”¹²

The microbiota-gut-brain axis

An aspect of the microbiome that is often overlooked is its effect on the brain. One study found that the microbiomes of patients with major depressive disorder (MDD) differed significantly from those in healthy controls. When the microbiomes of MDD patients were transplanted into germ-free mice, the mice displayed depression-like behaviors. To the contrary, when germ-free mice were transplanted with microbiomes from healthy patients, there was no behavior change.

“The gut microbiome is an increasingly recognized environmental factor that can shape the brain through the microbiota-gut-brain axis.…” concluded the researchers. “This study demonstrates that dysbiosis of the gut microbiome may have a causal role in the development of depressive-like behaviors, in a pathway that is mediated through the host’s metabolism.”¹³ No doubt, dysbiosis plays a role in canine and feline behavioral issues.

One way the microbiome affects the brain is the fact that certain intestinal bacteria produce and deliver neuroactive substances such as serotonin and gamma-aminobutyric acid (GABA). “Preclinical research in rodents suggested that certain probiotics have antidepressant and anxiolytic activities.”¹⁴ In addition, three double-blind, placebo-controlled trials studied the effect of probiotics on the stress responses in healthy medical students before exams. They found that probiotics may reduce stress reactivity in the paraventricular nucleus through vagal afferent signaling.¹⁵ Another study found that chronic administration of probiotic L. rhamnosus (JB-1) to mice caused a reduced level of anxiety and depression-like behavior. The probiotics induced changes in the GABAergic system in regions of the brain known to involve these behaviors. The researchers further found that a vagotomy prevented the effects of the probiotic, confirming the vagal signaling theory.¹⁶

Probiotics and the urinary tract

In a recent study, five lactobacillus strains (L. gasseri, L. rhamnosus, L. acidophilus, L. plantarum, L. paracasei,) were tested in vitro against four uropathogens common in infantile urinary tract infections. All the Lactobacillus strains showed moderate antimicrobial activities against the uropathogens.²¹ An intriguing case-controlled study involved the ingestion of fermented milk products in Japan. The researchers concluded: “It was strongly suggested that the habitual intake of lactic acid bacteria reduces the risk of bladder cancer.”²²

Probiotics and mutagen detoxification

In an early study of fermented milk products, 11 healthy subjects were put on a standardized diet that included consuming fried beef patties twice daily. For the first three days (Phase 1), the subjects were given Lactococcus (non-probiotic) fermented milk. During Phase 2, the subjects drank L. acidophilus fermented milk. The total fecal and urinary mutagen excretion (a cancer-causing chemical that is, or has been, excreted in the urine) on Day 3 during Phase 2 was 47% lower compared to Day 3 of Phase 1, indicating the possible role of probiotics in preventing cancer.²³

Probiotics as nutrients

According to Stedman’s Medical Dictionary²⁴ a nutrient is “a constituent of food necessary for normal physiologic function.” The term “essential nutrients” refers to “nutritional substances required for optimal health. These must be in the diet, because they are not formed metabolically within the body.” In my opinion, given the research explored in this article, probiotics meet these definitions. I am not alone in my assertion. “The health and well-being of companion animals, just as their owners, depends on the gut microbes…. Specific probiotic strains and/or their defined combinations may be useful in canine and feline nutrition, therapy, and care.”²⁵ Probiotics are essential nutrients for dogs and cats that are not contained in conventional diets, and must be supplemented regularly throughout life in order to maintain or regain health.

Microbiome and obesity

The metabolic activity of the microbiome is especially demonstrated by its effect on fat accumulation in the body. One study utilized four sets of human twins, one of whom was obese and the other lean. When a fecal transplant of the “lean” bacteria was made into germ-free mice, the mice remained thin. However, a fecal transplant of the “obese” bacteria into germ-free mice resulted in obese mice. Moreover, obese mice became thin when housed with thin mice apparently due to coprophagia.¹⁷ Another interesting study found that fecal transplants from conventionally raised mice into germ-free mice resulted in a 60% increase in body fat content and insulin resistance within 14 days despite reduced food intake. According to the researchers, “Our findings suggest that the gut microbiota is an important environmental factor that affects energy harvest from the diet and energy storage in the host.”¹⁸

Probiotics and pancreatitis

A randomized, double-blind, placebo controlled trial in human patients with acute pancreatitis found that “Supplementary L. plantarum 299 was effective in reducing pancreatic sepsis and the number of surgical interventions.”¹⁹ A similar study in dogs looked at experimentally-induced severe pancreatitis and compared ecoimmunonutrition, parenteral nutrition, and elemental enteral nutrition. (Ecoimmunonutrition refers to the feeding of L. plantarum-containing formula.) The probiotic treated dogs experienced lower levels of increase in serum amylase, ALT, AST, and plasma concentrations of endotoxin. They also had suppressed pancreatic and ileal histopathologic changes. Bacterial translocation was also decreased in the probiotic treated dogs.²⁰

Conclusion

We have seen that a well-balanced microbiome with numerous, diverse bacteria is important to an animal’s health. We have also explored the many commonly-used modern medications that can disrupt a pet’s GI bacterial equilibrium, leading to dysbiosis and leaky gut. And now we know how the use of probiotics can improve the health of well animals and effectively address a multitude of diseases. Probiotics truly are the missing nutrients in the diets of our dogs and cats.

¹Manninen TJK, et al. “Alteration of the canine small-intestinal lactic acid bacterium microbiota by feeding of potential probiotics”. Appl Environ Microbiol. 2006;72(10):6539-6543.

²Baillon M-LA, Marshall-Jones ZV, Butterwick RF. “Effects of probiotic Lactobacillus acidophilus strain DSM13241 in healthy adult dogs”. Am J Vet Res. 2004;65.3:338-343.

³Pasupathy K, Sahoo A, Pathak NN. “Effect of lactobacillus supplementation on growth and nutrient utilization in mongrel pups”. Archiv für Tierernaehrung. 2001;55(3):243-253.

⁴Marshall-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;67:1005–1012.

⁵Rastall RA. “Bacteria in the gut: friends and foes and how to alter the balance”. J. Nutr. 2004;134:2022S-2026S.

⁶Honneffer JB, Minamoto Y, Suchodolski JS. “Microbiota alterations in acute and chronic gastrointestinal inflammation of cats and dogs” World J Gastroenterol. 2014;20(44):16489-97.

⁷Suchodolski JS, et al. “The fecal microbiome in dogs with acute diarrhea and idiopathic inflammatory bowel disease”. PLoS One. 2012;7(12):e51907.

⁸Benyacoub J, Czarnecki-Maulden GL, Cavadini C, et al. “Supplementation of food with Enterococcus faecium (SF68) stimulates immune functions in young dogs”. J Nutr 2003;133:1158–1162.

⁹Majamaa H, Isolauri E. “Probiotics: a novel approach in the management of food allergy”. J Allergy Clin Immunol. 1997;99(2):179-185.

¹⁰Kalliomäki M, et al. “Probiotics and prevention of atopic disease: 4-year follow-up of a randomised placebo-controlled trial”. Lancet. 2003;361(9372):1869-1871.

¹¹Marsella R, Santoro D, Ahrens K. “Early exposure to probiotics in a canine model of atopic dermatitis has long-term clinical and immunological effects”. Vet Immunol Immunopathol. 2012;2:185–189.

¹²Wang F, Zhang C, Zeng Q. “Gut microbiota and immunopathogenesis of diabetes mellitus type 1 and 2”. Front Biosci (Landmark Ed). 2016;21:900-6.

¹³Zheng P, et al. “Gut microbiome remodeling induces depressive-like behaviors through a pathway mediated by the host’s metabolism”. Mol Psychiatry. 2016 Jun;21(6):786-96.

¹⁴Evrensel A, Ceylan ME. “The Gut-Brain Axis: The Missing Link in Depression”. Clin Psychopharmacol Neurosci. 2015;13(3):239–244.

¹⁵Takada M, et al. “Probiotic Lactobacillus casei strain Shirota relieves stress‐associated symptoms by modulating the gut–brain interaction in human and animal models”. Neurogastroenterol Motil. 2016 Jul;28(7):1027-36.

¹⁶Bravo JA, et al. “Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve”. Proc Natl Acad Sci U S A. 2011;108(38):16050-16055.

¹⁷Ridaura F, et al. “Gut microbiota from twins discordant for obesity modulate metabolism in mice”. Science, 2013; 341(6150):1241214.

¹⁸Bäckhed F, et al. “The gut microbiota as an environmental factor that regulates fat storage”. Proc Natl Acad of Sci U.S.A., 2004; 101(440;15718-15723.

¹⁹Olah 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; 89:1103-1107.

²⁰Xu GF, Lu Z, Gao J, et al. “Effect of ecoimmunonutrition support on maintenance of integrity of intestinal mucosal barrier in severe acute pancreatitis in dogs”. Chin Med J. 2006; 119:656-661.

²¹Shim YU, Lee SJ, Lee JW. “Antimicrobial activities of Lactobacillus strains against uropathogens”. Pediatr Int, 2016; Feb 10. Doi: 10.1111/pet.12949.

²²Ohashi Y, et al. “Habitual intake of lactic acid bacteria and risk reduction of bladder cancer”. Urologia internationalis, 2002; 68(4):273-280.

²³Lidbeck A, et al. “Effect of lactobacillus acidophilus supplements on mutagen excretion in faeces and urine in humans”. Microbial Ecology in Health and Disease, 1992;5(1):59-68.

²⁴Stedman’s Medical Dictionary (27^th ed). 2000, Baltimore, MD; Lippincott Williams & Wilkins.

²⁵Grześkowiak L, Endo A, Beasley S, Salminen S. “Microbiota and probiotics in canine and feline welfare”. Anaerobe. 2015;34:14-23.

This article has been peer reviewed.