Abelmoschus Manihot flowers inhibit dysbiotic Enterobacteriaceae expansion by promoting Clostridium bolteae-mediated hypoxia restoration.

Abstract

BACKGROUND: Inflammatory bowel disease (IBD) is a chronic inflammatory disease that has become prevalent worldwide. Excessive expansion of Enterobacteriaceae is a key feature of dysbiosis in IBD patients, which further exacerbates intestinal inflammation. Therefore, inhibiting the dysbiotic expansion of Enterobacteriaceae is a promising strategy for the treatment of IBD. We investigated the effects of Abelmoschus manihot (A. manihot) flowers on the intestinal microbiota during colitis. RESULTS: We found that A. manihot flowers are capable of ameliorating murine colitis and suppressing Enterobacteriaceae expansion, not by direct action but rather by promoting the growth of Lachnospiraceae, particularly Clostridium bolteae. Bacterial depletion and recolonization confirmed that Clostridium bolteae restored colonic hypoxia via PPAR-γ activation, creating an environment unfavorable for Enterobacteriaceae growth and reducing inflammation. Moreover, intestinal hypoxia is vital for Clostridium bolteae colonization and its effect on Enterobacteriaceae expansion, which involves crosstalk between gut microbe colonization and intestinal oxygen homeostasis. CONCLUSION: Overall, our study provides evidence that modulating the gut microbiota to restore intestinal hypoxia is a promising therapeutic strategy for suppressing Enterobacteriaceae proliferation in the inflamed gut and for ameliorating intestinal inflammation, which could be applied to other Enterobacteriaceae-related diseases. Video Abstract.