Department of Veterinary Clinical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg, Denmark
Introduction
Elie Metchnikoff, who is considered the inventor of probiotics proposed that the life span of consumers of fermented dairy products was prolonged because the acid-producing organisms would prevent “fouling” in the large intestine.1
Inspired by the use of fermented products, strategies for supporting health have since been proposed. Prebiotics are nutrients (commonly carbohydrates and fiber) that are able to favor “beneficial” gut bacteria, probiotics are defined as live microorganism that, when given in adequate amounts, confer a health benefit to the host and synbiotics are a combination of pro- and prebiotics.2 Currently, only Enterococcus faecium NCIMB 10415 and Enterococcus faecium DSM 10663/NCIMB 10415 have been approved for use as food additives in dogs and cats by the European Food Safety Authority (EFSA).3 Probiotics are thought to confer intestinal health by several mechanisms; displacement of intestinal pathogens, production of antimicrobial substances, maintaining a local intestinal environment unsuitable for pathogenic bacteria (for example decreasing pH), and enhancement of immune function and responses. These effects are partly conferred by bacteria-derived metabolites such as short chain fatty acids (SCFA), known to provide energy for enterocytes and the host, regulate intestinal motility, and modulate immune function. Other favourable metabolites are indole and secondary bile acids that support immune homeostasis and intestinal barrier.3
Intestinal dysbiosis, is an alteration in the composition, abundance and diversity of the gut microbiota leading to altered physiological pathways compared with healthy individuals. Intestina dysbiosis result in compromised intestinal barrier function through decreased production of anti-inflammatory metabolites, altered mucosal fluid secretion and increased production of toxins. Dysbiosis can be primary or develop secondary to other disease, environmental changes or antibiotic treatment. Depending on timing and the host’s ability to cope with the challenges, it may lead to severe chronic alterations of the whole-body metabolism.
Molecular-phylogenetic studies have revealed the presence of intestinal dysbiosis in dogs and cats with acute and chronic diarrhea. Following the realization that there exist an intense and complex communication between the host and the intestinal microbiota, development of targeted and possibly more potent probiotic strains has been intensified. Furthermore, because intestinal dysbiosis in early childhood is closely linked to increased risk of developing allergies, obesity, and inflammatory bowel disease in adulthood, it has been realised that probiotics may not only act locally in the GI tract but may have more systemic effects.
Randomized blinded studies investigating the effect of probiotics in dogs and cats are still limited and the variety of strains or combinations with prebiotics makes comparisons difficult.
Probiotics and Acute Diarrhea
One of the best investigated areas of probiotics use in dogs and cats are the use for preventing or treating acute or stress-related diarrhea, however, most studies are characterized by a low number of animals and presence of confounding factors. A recent doubleblinded randomized placebo-controlled study including 773 shelter dogs showed significantly fewer days scored as diarrhea relative to the dogs total stay, in synbiotic (Enterococcus faecium NCIMB 10415 4b1707, 2 x 109 colony forming units [CFU/g])treated dogs (2.0%) compared with placebo treated dogs (3.2%, p=0.0008)4 In shelter cats (n=217), administration of Enterococcus faecium strain SF68 (2 x 109 CFU/g) was associated with a lower percentage of cats (7.4%) having stress-related diarrhea for more than 2 days compared with placebo (20.7%, p=0.03).5 However, when all outcomes were included in the analysis (0–5 days with diarrhea), there were no significant difference between groups.5 In the same study no effect was found in dogs, but this could be due to a very low prevalence of stress-related diarrhea in both groups.5
Probiotics and Chronic Diarrhea
One randomized controlled trial evaluated clinical and histological response rates in dogs with moderate to severe IBD.6 The dogs were treated with either probiotics (VSL #3, multi-strain formulation, 2 x 1011 CFU/g, n=10) or a combination of prednisone and metronidazole (n=10). The two groups had similar remission rates, but the median time for remission was 6 days longer for the probiotic group. Furthermore, there were indications that probiotics induced sustained immune modulatory effects. In cats, an open-label study found a synbiotic to improve the mean fecal score (6.0 to 4.4, p<0.001) for cats completing the study (n=53).7
Probiotics and Constipation
Preliminary results presented at conferences indicate that probiotic (Sivoy, VSL #3, 2 x 1011 CFU/g) significantly improve the feline chronic enteropathy activity index and histology scores in cats diagnosed with chronic idiopathic constipation and megacolon.8
Probiotics and Antibiotic Treatment
Antibiotic treatment results in dramatic changes in gut microbiota composition and in some patients this can develop into a more chronic intestinal dysbiosis. Probiotics support restoration of the commensal flora.
Probiotics and Atopic Dermatitis
A recent meta-analysis of randomized clinical trials evaluating the effects of synbiotics for the treatment of atopic dermatitis in children found that there was convincing evidence of beneficial effects of supplementing mixed strains of bacteria to children of more than one year of age. A recent double-blinded placebo-controlled trial testing the use of a probiotic strain (Lactobacillus sakei, 2 x 109 CFU/g) administered for 2 months to research dogs with atopic dermatitis significantly reduced canine atopic dermatitis extent and severity index (CADESI-03) and Pruritus Visual Analogue Scale (PVAS) scores of treated dogs (n=28) compared with placebo (n=10).9
Future Areas for Use of Probiotics in Dogs and Cat
Probiotics and Mental Disease
Through the recently established gut microbiota-brain axis, the gut microbiota can play an important role in modulating behaviour and cognitive development through the production of hormones, immune factors, and metabolites. This again implies that changing the gut microbiota could directly affect the brain’ s physiological, behavioural, and cognitive functions and ultimately prevent or cure brain diseases. Some studies have identified decreased stress-related diarrhea in pets supplemented with probiotics and it is likely that more studies in this field will emerge in near future.
Probiotics for Obesity and Type 2 Diabetes
The gut microbiota can affect the degree of energy harvest in an individual. For example, lean mice receiving gut microbiota transplantation from phenotypically obese mice start to gain weight. Obese individuals also seem to have a different gut microbiota compared with lean, but whether this is a cause or effect is uncertain.
Conclusions
Recent technological developments permitting a more in-depth phylogenetic analysis of the intestinal microbiota has provided a more global insight into the complex interaction between the host, the intestinal microbiota, and probiotics. This has furthered our understanding of the metabolic mechanisms supporting the host and will hopefully continue to increase our understanding and add to targeted probiotic development. It should, however, be noted, that probiotics are, in most countries, considered food supplements, not strictly regulated. Studies have shown that not all products pass quality testing, some do not contain what they declare, some products do not contain live bacteria and some even contain pathogenic bacteria.10
References
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6. Rossi G, Pengo G, Caldin M, Piccionello AP, Steiner JM, Cohen ND, Jergens AE, Suchodolski JS. 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:e94699.
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8. Rossi G, Jergens A, Cerquetella M, Berardi S, Pengo G, Suchodolski J. The effect of the probiotic Sivoy™ on clinical and histopathological parameters in cats with chronic idiopathic constipation and megacolon. J Vet Intern Med. 2015;29:1189.
9. Kim H, Rather IA, Kim H, Kim S, Kim T, Jang J, Seo J, Lim J, Park Y. A double blinded placebo controlled-trial of a probiotic strain lactobacillus sakei Probio-65 for the prevention of canine atopic dermatitis. J Microbial Biotechnol. 2015;25:1966–1969.
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