Effect of butyrate on the development of intestinal inflammation in experimental mouse model
Ing. Barbora Draboňová
Czech University of Life Sciences Prague
Faculty of Agrobiology, Food and Natural Resources
Department of Food Science
Introduction
The human body, including the gut, skin and other mucous membranes, is populated by a huge number of microorganisms, collectively referred to as the microbiota. This ecosystem, comprising the genome of bacteria, fungi, viruses, and parasites, actively influences many host functions, including circadian rhythms, nutrition, metabolism, and immunity (Lynch & Hsiao 2019). Among these many microbial communities that populate the human body, the gut microbiome is emerging as an important factor influencing host health.
Of the environmental factors that contribute to the development and progression of autoimmune diseases, diet is the least variable and most controllable factor and as such opens up a wide range of therapeutic possibilities. In the search for therapeutic targets, the main research focuses on probiotic bacteria or beneficial metabolites (Serban 2015).
Nutrition appears to be the main driver of gut dysbiosis in genetically predisposed individuals. Diet or dietary components represent a relatively simple and safe strategy to regain control of many, not only intestinal, immune-mediated diseases.
In the case of micro-ecological imbalance, intestinal microorganisms and their metabolites act on the genetically susceptible host to activate immune responses that may influence the development of inflammatory bowel diseases (IBD), including ulcerative colitis (UC). UC is a chronic, relapsing, inflammatory bowel disease. The aetiology of the disease involves a combination of genetic predisposition and environmental factors such as inadequate nutrition, overuse of antibiotics, stress and imbalance of the gut microbiota (called dysbiosis). Current theories of UC pathogenesis suggest that it is pathological changes in gut microbial composition that trigger an abnormal mucosal immune response in genetically predisposed individuals, leading to the development of intestinal inflammation. The diet of our ancestors consisted of much more digestible fibre than the diet of today’s society. From an evolutionary perspective, the human genome and its physiological and nutritional requirements are not well aligned with modern dietary habits. Fibre in the large intestine is anaerobically fermented by intestinal bacteria, which produce short-chain fatty acids as metabolic by-products. SCFAs are important for maintaining intestinal homeostasis and their reduction may contribute to intestinal pathophysiology. UC patients tend to have reduced numbers of bacteria producing short-chain fatty acids (butyrate, propionate, acetate), which, in conjunction with the gut microbiota, are important modulators of immune function. In the gut, SCFAs are an important source of nutrients for epithelial cells and are modulators of immune responses that support intestinal barrier function. Butyrate is the salt of butyric acid, which is formed by fermentation of dietary fiber and is a significant source of energy for colonocytes. It also lowers pH in the colon, increases mineral absorption, reduces ammonia absorption and inhibits pathogen growth. It improves intestinal barrier function by stimulating the production of mucin and antimicrobial peptides (Riviére et al. 2016).
The aim of the study
The aim of my study was to determine whether butyrate would have a protective effect on acute intestinal inflammation induced in conventional BALB/c mice strain by administration of dextran sulfate sodium (DSS) in a human UC model.
Results
Acute UC was induced in animals by administration of 2.5% DSS in drinking water for 7 days. Butyrate was administered orally. Histological slides stained with hematoxylin-eosin were evaluated. No inflammation was observed in control healthy mice when the degree of intestinal mucosal damage was assessed. The mucosa in the colon descendens showed preserved crypts and surface epithelium (Figure 1). We observed the same result in mice treated with butyrate for two weeks (Figure 2). The protective effect of butyrate was observed in mice after 1-week administration of butyrate and then after 1-week administration of DSS in butyrate solution (Figure 3). The same result was obtained in mice after 2-week administration of butyrate and then after 1-week administration of DSS (Figure 4). The conventional mice in the control group showed signs of severe inflammation after 7 days of DSS administration (Figure 5).
Conslusions
The results of the experiment demonstrated a protective effect of butyrate on the development of intestinal inflammation in an experimental mouse model of acute colitis. Experiments with conventional mice further confirmed that the DSS effect is linked to the presence of gut microbiota.
References
Lynch J. B., Hsiao E. Y. (2019). Microbiomes as sources of emergent host phenotypes.
Science. 365: 1405–1409.
Rivière A., Selak M., Lantin D., Leroy F., De Vuyst L. (2016). Bifidobacteria and butyrate-producing colon bacteria: importance and strategies for their stimulation in the human gut. Frontiers of Microbiology, 7:979. doi: 10.3389/fmicb.2016.00979.
Serban D. E. (2015). Microbiota in Inflammatory Bowel Disease Pathogenesis and Therapy: Is It All About Diet? Nutrition in Clinical Practice. 30(6):760–79. doi: 10.1177/0884533615606898.
