Interest in the use of probiotics has continued to grow over the past 10 years. A PubMed search on “probiotics” brings up over 18,000 articles, with nearly 650 published in early 2018. With increasing knowledge of the gastrointestinal (GI) and other microbiomes there is increasing interest in probiotic use.

When practitioners consider the use of probiotics, it is often for pets with chronic or acute diarrhoea or possibly as adjunct therapy for pets on antibiotics. Most commercial probiotic products are marketed for gastrointestinal disorders. Ideally the choice should be made based on scientific evidence.

Definition

A panel of the International Scientific Association for Probiotics and Prebiotic slightly modified the FAO/ WHO definition of probiotics to: “live microorganisms that, when administered in adequate amounts, confer a health benefit on the host”. While fermented foods have benefits, the benefits of the food could not be separated from those of the microorganisms, so these foods are not considered probiotics. Similarly, while faecal microbiota transplantation has shown benefits, the lack of identification of the microorganisms used excluded this from the definition of probiotic other than when a defined mixture of microbes is used. The term probiotic has also been misused on products as diverse as mattresses, shampoos, face creams and aftershave and shampoos containing yoghurt.

Prebiotics are nutrient sources for beneficial bacteria included in a food or supplement, e.g., fructooligosaccharide or inulin. When a prebiotic is included with probiotics it is termed a synbiotic.

Core Benefits

While the decision to use a probiotic should be made on evidence that the microorganisms and the amount have a benefit for the disorder treated, there is now evidence of effects which can be ascribed to some probiotic strains in general. These are strains used at a functional dose as a food or supplement and for humans include Bifidobacterium (adolescentis, animalis, bifidum, breve and longum) and Lactobacillus (acidophilus, casei, fermentum, gasseri, johnsonii, paracasei, plantarum, rhamnosus and salivarius).

In humans, the beneficial dose is 1x109 colony forming units/serving or per day. The intended benefit is supporting a healthy gut microbiota, although this benefit is not well defined. Human disorders where core effects may help include infectious diarrhoea, antibiotic-associated diarrhoea, irritable bowel syndrome, and ulcerative colitis. Mechanisms of action which may be wide spread among probiotics include resistance of pathogen colonization, competitive exclusion of pathogens, production of short chain fatty acids, regulation of intestinal transit, normalization of microbiota, and increased turnover of enterocytes. Core benefits from non-strain-specific microorganisms have not been described in veterinary patients, although there may be general benefits for the gastrointestinal tract (GIT) and the microbiome.

The Microbiome

The microbiome is composed of microbes in and on the body on a mucosal or skin surface and their environment and has been termed the second genome. It is a source of genetic diversity, a modifier of disease, an essential component of immunity, and influences metabolism and modulates drug interactions.

The GIT contains tens of trillions of microbes, outnumbering host cells by ten fold. Each individual has its own unique intestinal microbiome, with variation along the GIT. The density and diversity of species increase exponentially from the stomach to highest numbers in the colon. The phyla Actinobacteria, Bacteroides, Bififobacteria, Firmicultes, Fusobacteria, and Proteobacteria comprise most of the organisms.

By fermenting fibre (e.g., in prebiotics), microbes produce short chain fatty acids (SCFA), including butyrate. Butyrate provides energy for colonocytes, affects the GIT barrier function, has anti-inflammatory and anti-oxidative potential, plays a regulatory role on transepithelial fluid transport, reinforces the epithelial defence barrier, modulates visceral sensitivity, intestinal motility, effects gene regulation, and has a role in the prevention and inhibition of human colorectal cancer.

Probiotics can induce microbiota changes in the large intestine, but these changes are usually minor, transient and dose dependent. High doses over prolonged periods of time are usually required to maintain viable counts of probiotic species. Lactobacillus spp increased from 1% to 2.5% of the total bacteria after administration of a multi-species probiotic containing several Lactobacillus spp. A mucosa-adherent probiotic may affect the microbiota more significantly; administration of VSL#3 to mice resulted major changes in ileal microbiota.

Acute, Antibiotic and Stress-related Associated Gastroenteritis

Several studies in dogs and cats with acute gastroenteritis or idiopathic diarrhoea with multi-species probiotic, Bifidobacterium animalis, Enterococcus (E) faecium SF68, or Lactobacillus acidophilus, sometimes used with a prebiotic or metronidazole, have shortened duration of diarrhea or decreased incidence of signs in at risk (rescue shelter) dogs or cats.

In cats given clindamycin, those also given a multi-strain synbiotic had better appetites and were more likely to have completed the treatment due to less vomiting. The yeast Saccharomyces boulardii shortened the duration of diarrhoea in dogs given lincomycin and prevented diarrhoea when given concurrently.

Enterococcus faecium SF68 may also have a benefit in puppies with parvovirus enteritis, and in stress related diarrhoea in sled dogs and in kennelled dogs.

Chronic Diarrhea

Dogs

Dogs with chronic enteropathy (CE) or inflammatory bowel disease (IBD) may have decreased intestinal microbial diversity (dysbiosis). Enterococcus faecium significantly increased the faecal bacterial richness and diversity of dogs with IBD, which became more similar to healthy dogs. Supplementation with Lactobacillus spp to dogs with food responsive diarrhoea showed beneficial effects on intestinal cytokines and microbiota, although the changes were not associated with the clinical response as the dogs had responded to a hydrolysed diet.

A probiotic containing multiple bacteria (VSL#3, now Vivomixx) given to 10 dogs with chronic IBD significantly decreased clinical scores, histological scores and CD3+ T-cell infiltration, and normalized dysbiosis.

Cats

There are fewer probiotic studies in cats with chronic diarrhoea. A synbiotic with seven microbial strains improved stool quality in cats with chronic diarrhea. Lactobacillus and E. faecium given to juvenile cheetahs increased body weight and improved faecal quality compared to a control group.

Other Potential Uses

Dental Disease

Dental plaque, a microbial biofilm on the tooth surface, is a main cause of dental pathology. A probiotic with Lactobacillus acidophilus LA-5 and Bifidobacteria bifidum BB-12 had in vitro bacteriocidal effects on pathogenic species from supragingival sites of dogs with dental disease. Topical L. brevis CD2 in dogs reduced gingival inflammatory infiltrates.

Weight Management

The gut microbiota differs between obese and lean individuals and is a potential determinant of obesity. Probiotics may affect the gut microbiota to modulate obesity. A meta-analysis of human studies on probiotics as a treatment for weight loss indicated limited efficacy for decreasing body weight and body mass index; however, a more recent meta-analysis concluded that probiotics or prebiotics (but oddly, not synbiotics) compared to placebo were associated with significant decreases in human weight and fat mass. Short-term use of E. faecium SF68 dietary supplementation in eight cats had no effect on food intake, bodyweight, body composition or metabolic parameters in overweight and obese cats; however, longer, larger studies would be useful.

Chronic Kidney Disease (CKD)

In humans with CKD, decreased azotaemia was seen with 6-month probiotic treatment. The probiotic VSL#3 plus a renal diet in 60 dogs with CKD increased the glomerular filtration after 2 months compared to controls on just the renal diet. Similarly, in azotaemic cats, serum urea nitrogen and creatinine concentrations decreased after 60 days probiotic supplementation; although concurrent treatments varied and the relationship to quality of life or survival time was not clear. In 10 cats with naturally occurring azotaemia, synbiotic supplementation had no effect on azotaemia compared to a control with prebiotic alone, although GFR was not measured. This same synbiotic supplementation decreased serum creatinine but not serum urea of 15 azotaemic large cats (e.g., tigers, lions, etc.) after 6 months.

Calcium Oxalate Uroliths

Oxalate is eliminated through urinary excretion, forming insoluble calcium oxalate in the GIT and faecal elimination, or by oxalate degradation by gastrointestinal microorganisms. Some probiotics containing Lactobacillus spp or Oxalobacter formigenes degrade GI oxalate, resulting in decreased absorption and urinary excretion. The prevalence of O. formigenes in faeces from dog with calcium oxalate uroliths was 25%, 50% in healthy dogs and 75% in healthy dogs of breeds not at risk for oxalate uroliths. The faeces of 86% of healthy cats had the genes for O. formigenes, although the association with oxalate urolithiasis has not yet been explored. Further investigations need to determine whether there is a direct link between the lack of oxalate- degrading bacteria and hyperoxaluria, if absence is a risk factor for urolithiasis, and if supplementation decreases the risk.

Canine Atopic Dermatitis (AD)

Human and dogs with AD have a skin microbiota dysbiosis, with a lower diversity of microbial populations than healthy individuals. Whether altered microbial populations are the cause or the effect of inflammatory skin conditions is not yet known; however, the microbiome has an important role in skin health. Studies on the prevention or treatment of canine AD have had mixed results on clinical signs. One study showed a decrease in prednisolone use in dogs with AD given Lactobacillus paracasei K 71 compared to those on cetirizine hydrochloride.

References

References are available upon request.