Chlorogenic Acid Ameliorates Post‐Infectious Irritable Bowel Syndrome by Regulating Extracellular Vesicles of Gut Microbes

Abstract Post‐infectious irritable bowel syndrome (PI‐IBS) occurs after acute infectious diarrhea, and dysbiosis can be involved in its pathogenesis. Here, the role of chlorogenic acid (CGA) is investigated, a natural compound with several pharmacological properties, in alleviating PI‐IBS in rats. It is elucidated that the gut microbiota plays a key role in PI‐IBS pathogenesis and that rectal administration of CGA alleviated PI‐IBS by modulating the gut microbiota and its metabolites. CGA supplementation significantly increased fecal Bacteroides acidifaciens abundance and glycine levels. Glycine structurally altered B. acidifaciens extracellular vesicles (EVs) and enriched functional proteins in the EVs; glycine‐induced EVs alleviated PI‐IBS by reducing inflammation and hypersensitivity of the intestinal viscera and maintaining mucosal barrier function. Moreover, B. acidifaciens EVs are enriched in the brain tissue. Thus, CGA mediates the mitigation of PI‐IBS through the gut microbiota and its metabolites. This study proposes a novel mechanism of signal exchange between the gut microenvironment and the host.