Details of Research Outputs

Gut microbiota dysbiosis is causally related to inflammatory bowel disease (IBD), and increased levels of the gut metabolite ammonia have been proposed to contribute to IBD development. In this study, we aimed to clarify the anticolitis mechanism of gallic acid (GA) based on its ability to trap the deleterious metabolite ammonia and improve gut microbiota. Aminated product was detected in the fecal samples of mice after oral gavage of gallic acid (GA) and identified as 4aminosubstituted gallic acid (4NHGA), thus confirming the ability of GA to trap ammonia in vivo. Then, we compared the beneficial effects of GA and 4NHGA on dextran sulfate sodium (DSS)induced colitis mouse and found that both compounds managed to alleviate colitis phenotypes, indicating ammonia trapping had no adverse effect on the original anticolitis activity of GA. In addition, both GA and 4NHGA improved the gut microbiota dysbiosis induced by DSS, and fecal microbiota transplantation was subsequently performed, which further revealed that the gut microbiota mediated the anticolitis activity of both GA and 4NHGA. In summary, this study clarified that GA alleviated colitis by targeting both the symptoms and root causes: it directly reduced the deleterious metabolite ammonia by forming aminated metabolites without compromising the original anticolitis activity, and it also improved gut microbiota dysbiosis, which in turn contributed to the alleviation of colitis. Since the GA structure is presented in various polyphenols as a common building block, the novel anticolitis mechanism obtained from GA may also apply to other complex polyphenols. IMPORTANCE The dysbiosis of the gut microbiota and its metabolism directly cause the emergence of IBD. In this study, we aimed to clarify the anticolitis mechanism of GA in sight of gut microbiota and its metabolite ammonia. We discovered that GA directly captured and reduced the harmful metabolite ammonia in vivo to produce the aminated metabolite 4NH2GA, while the amination of GA had no adverse effect on its initial anticolitis activity. In addition, both GA and its aminated metabolite improved the gut microbiota in colitis mice, and the modified gut microbiota, in turn, helped to relieve colitis. Since the GA structure is presented in diverse polyphenols as a common building block, the novel anticolitis mechanism targeting the symptoms and root causes might also apply to other complex polyphenols.