Research at IMS finds that the metabolite acetate or-4chestrates interactions between IgA and selective intestinal micro-organisms-a finding that has important implications for health.Anyone who has had a health check knows that their blood can say a lot about their well-being. Perhaps sur-prisingly, so too can the unique community of microbes inhabiting each individual. An imbalance in gut bacteria, for example, has been linked to conditions as wide rang-ing as obesity and Alzheimer’s disease. Understanding how microbial populations are regulated could provide crucial insight into ways to both maintain health and treat disease.Bacteria in the gut play a plethora of roles, from break-ing down complex molecules derived from the food we eat to programming the immune system. Researchers like Hiroshi Ohno, Team Leader of the Laboratory of Intestinal Ecosystem at IMS, have theorised that these seemingly dis-parate actions may actually converge to maintain bacterial balance.One way that this could transpire is through metabo-lites called short-chain fatty acids (SCFAs), which regu-late various actions of the immune system, including the production of IgA. As well as being the most abundant immunoglobulin in the body, IgA is known to regulate the composition and function of gut bacteria.“We hypothesized that SCFAs affect IgA in the intes-tines, which could have important downstream implica-tions on resident bacteria,” Ohno said.In their study published in Nature, Ohno and colleagues tested this theory by exploring the effects of three major SCFAs in the intestine: propionate, butyrate and acetate. After feeding the rodents special diets that selectively in-creased each SCFA in the large intestine, they found that only one-acetate-had an effect on IgA.In addition to increasing IgA levels, acetate also altered the binding capacity of the immunoglobulin to bacterial cells. The latter action proved surprisingly specific. Experi-ments in mice devoid of all micro-organisms except for ei-ther a beneficial strain called Bacteroides thetaiotaomicron or a potentially harmful one called Escherichia coli revealed that acetate directs IgA binding only to the latter species.The purpose of acetate’s influence on interactions between IgA and selective microbes could be to control the latter’s entry into the body. By imaging fluorescently-labelled E. coli, the researchers indeed found that binding of IgA prevents the harmful bacteria from colonising and infiltrating the cells lining the intestinal tract.Given that metabolites like acetate can be derived di-rectly from the food we eat, especially indigestible dietary fibres, these findings suggest that our diet is a simple yet effective portal through which to rebalance our intestinal microbiota. This could be especially important for the elderly, patients with irritable bowel syndrome and under-nourished children, who have altered populations of IgA-bound bacteria.However, given the sparse research on metabolites to date, Ohno plans to focus on further understanding the interactions between these small molecules and the body’s micro-organisms and their consequences on health.Figure: Acetate orchestrates interactions be-tween IgA and bacteria in the gut(Left) In steady state, IgA nonpreferentially interacts with a beneficial strain such as Bacteroides thetaiotaomicron and a potentially harmful one such as Escherichia coli.(Right) The presence of high acetate both increases IgA levels and redirects the immunoglobulin’s preference to E. coli.Original paper:Takeuchi T, Miyauchi E, Kanaya T, Kato T, Nakanishi Y, Watanabe T, Kitami T, Taida T, Sasaki T, Negishi H, Shimamoto S, Matsuyama A, Kimura I, Williams IR, Ohara O, Ohno H. Acetate differentially regu-lates IgA reactivity to commensal bacteria. Nature 595, 560-564 (2021)Hiroshi OhnoA conductor of gut bacteria revealed
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