The multiple beneficial effects on human health of the short-chain fatty acid butyrate, synthesized from non-absorbed carbohydrate by colonic microbiota, are well documented. At the intestinal level, butyrate plays a regulatory role on the transepithelial fluid transport, ameliorates mucosal inflammation and oxidative status, reinforces the epithelial defense barrier, and modulates visceral sensitivity and intestinal motility. In addition, a growing number of studies have stressed the role of butyrate in the prevention and inhibition of colorectal cancer. At the extraintestinal level, butyrate exerts potentially useful effects on many conditions, including hemoglobinopathies, genetic metabolic diseases, hypercholesterolemia, insulin resistance, and ischemic stroke. The mechanisms of action of butyrate are different; many of these are related to its potent regulatory effects on gene expression. These data suggest a wide spectrum of positive effects exerted by butyrate, with a high potential for a therapeutic use in human medicine.
The development of the intestinal ecosystem is crucial for many gastrointestinal functions and body health. The intestinal ecosystem essentially comprises the epithelium, immune cells, enteric neurons, intestinal microflora, and nutrients. The coordinate interplay between all these components is the object of intensive research efforts to design new strategies for many intestinal and extraintestinal diseases. In this context, short-chain fatty acids (SCFAs), produced by intestinal microflora, represent a clear example of the importance of the intestinal ecosystem. SCFAs are organic acids produced by intestinal microbial fermentation of mainly undigested dietary carbohydrates, specifically resistant starches and dietary fiber, but also in a minor part by dietary and endogenous proteins. SCFAs are 2-carbon to 5-carbon weak acids, including acetate (C2), propionate (C3), butyrate (C4), and valerate (C5). SCFAs are essentially produced in the colon. The ratio of SCFA concentrations in the colonic lumen is about 60% acetate, 25% propionate, and 15% butyrate. As a result of increasing concentrations of acidic fermentation products, the luminal pH in the proximal colon is lower. This pH seems to boost the formation of butyrate, as mildly acidic pH values allow butyrate-producing bacteria to compete against Gram-negative carbohydrate-utilizing bacteria, such as Bacteroides. The ability to produce butyrate is widely distributed among the Gram-positive anaerobic bacteria that inhabit the human colon. Butyrate-producing bacteria represent a functional group, rather than a coherent phylogenetic group.
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