Dr Traj Nibber and Dr Anjan Nibber

Our gut contains billions of live bacteria, belonging to over a 1000 different species. In fact, the bacteria in our gut are thought to outnumber the number of cells of an adult person by 10-100 fold! These bacteria, or microbiota, play a crucial role in maintaining the delicate balance in the gut or homeostasis, including the metabolism of nutrients and the production of essential vitamins (K and B12). Gut microbiota can also prevent invasion of pathogenic bacteria by outcompeting them for adherence to mucosa and epithelium (the lining of the gut wall) for prime real estate. The composition of microbiota is ever changing and varies along the gastrointestinal tract (as the pH environment changes), and throughout life, as we eat different foods as children than as adults. Aberrant changes to the normal microbiota or dysbiosis have been implicated in a number of inflammatory conditions. Dysbiosis resulting in reduced bacteria diversity, dysregulation of immune cell differentiation, altered regulation of intestinal epithelial cell death mechanisms, and oxidative stress are just some of the pathogenic mechanisms hypothesized to lead to gastrointestinal discomfort. Over the last 20 years, the role of administering bacteria therapeutically has been extensively studied. Below we will summarize a number of therapeutic strategies including prebiotic, probiotics, synbiotics and postbiotics. 

Prebiotics

Prebiotics comprise nondigestible carbohydrates such as fructo-oligosaccharide, inulin and lactulose that have been fermented by gut bacteria. These carbohydrates selectively promote the development of commensal (friendly) bacteria in the gut. Furthermore, studies have shown that prebiotics can increase the production of short-chain fatty acids (SCFA) such as acetate, butyrate and propionate. The combination of increased gut microbiota and a production of SCFAs results in a decrease in colonic pH (the colon becomes more acidic), which can inhibit the ability of pathogenic bacteria to survive and bind to the intestinal wall. SCFAs act as fuel for the enterocytes the main cells comprising the gut lining, which therefore preserves the integrity of the gut lining and reducing “leaky gut”. One unique strain is Clostridicum butyricum a strain only found in Japanese formulation called Bio-3.  Currently, most of the evidence for the effectiveness of prebiotics has been conducted in animal models. 

Probiotics: 

Of the strategies discussed in this blog, probiotics have been the best studies. Probiotics comprise a single or a combination formulation of live bacteria, which are normal commensals of the gut – such as Lactobacillus and Bifidobacteria. The main benefits of probiotics can be conferred through the probiotics ability to outcompete pathogenic bacteria in the gut, and also by increasing gut barrier function. There is a growing body of evidence to show that probiotics can have a significant impact in the healing period, post gastrointestinal surgery. Probiotics have also been extensively studied in relation to skin health.

Synbiotics:

Synbiotics refer to a combination of prebiotics and probiotics. Studies have shown that this combination improves the survival of beneficial bacteria in the gut. Again the most commonly used probiotics include live Lactobacillus and Bifdobacteria, and the prebiotics fructo-oligosaccharide and inulin. Bio-3 a combination of three unique strains hitherto not found in Western probiotics. Together, these three strains combine to act not only as probiotics but as well as pre-biotics and synbiotics where the combination works better than individual strain.

Postbiotics:

A number of studies that shown that the health benefits of commensal bacteria do not necessarily require the bacteria to be alive. Postbiotics are soluble cell-wall components or metabolic byproducts released by live bacteria following lysis (cell death). These include enzymes, peptides, peptidoglycan derived products, polysaccharides and cell surface proteins. There are a number of factors that make postbiotics an attractive therapeutic strategy for gastrointestinal concerns. First, unlike probiotics, postbiotics are not live. This means that the possibility of transferring over antibiotic resistance genes to any pathogenic bacteria that is the in the gut is minimal. Second, the concern for bacterial validity which exists with probiotic production is not a factor for postbiotics which are stable and have a long shelf-life. Finally, postbiotics are active and stable over a wider range of pH, which is important as the pH through the gastrointestinal tract is highly variable. 

Conclusion:

There are a number of new and exciting potential therapeutic strategies for the management of gastrointestinal discomfort.  We hope that this has been a good introduction to some of the terms you may see in the literature. All of these strategies may have additional clinical use in the management of a range of other conditions such as skin health promotion and vaginal health, which we will explore in future blogs. Stay tuned!

References:

Aggeletopoulou I, Konstantakis C, Assimakopoulos F, Triantos C. The role of the gut microbiota in the treatment of inflammatory bowel diseases. Microbial Pathogenesis: 2019;137: 103774

Aguilar-Toala JE, Garcia-Varela R, Garcia HS, Mata-Haro v, Gonzalez-Cordova AF, Vallejo-Cordoba B, Hernandez-Mendoza A. Postbiotics: An evolving term within the functional foods field. Trends in Food Science and Technology. 2018;75:105-114

Saez-Lara MJ, Gomez-Llorente C, Plaza-Diaz J, Gil A, The role of probiotic lactic acid bacteria and bifidobacteria in the prevention and treatment of inflammatory bowel disease and other related diseases: a systematic review of randomized human clinical trials, BioMed Res. Int. 505878; 2015;22:https://doi. org/10.1155/2015/505878.