Clostridium bolteae suppresses Enterobacteriaceae expansion and restores gut microbiome homeostasis via disrupting siderophore-mediated iron acquisition

Intestinal inflammation and the related gut microbiome dysbiosis are becoming prevalent worldwide. Overgrowth of Enterobacteriaceae exacerbates intestinal inflammation and gut microbiome dysbiosis. Enterobacteriaceae secrets siderophore to acquire iron and survive in the iron-limited gut. Therefore, inhibiting the dysbiotic expansion of Enterobacteriaceae to restore gut microbiome homeostasis and alleviate intestinal inflammation by disrupting siderophore-mediated iron acquisition necessitate further investigation. We revealed that siderophore enterobactin is vital for Enterobacteriaceae-induced intestinal inflammation and gut microbiome dysbiosis. Furthermore, we found that commensal bacterium Clostridium bolteae (C. bolteae), a member of Lachnospiraceae, disrupts siderophore-mediated iron acquisition in Enterobacteriaceae and suppresses Enterobacteriaceae expansion. This strategy induces compensatory enterobactin synthesis, leading to the accumulation of enterobactin and energy depletion in Enterobacteriaceae. This work suggests that targeting siderophore-mediated iron acquisition pathway by commensal bacteria represents a promising strategy to suppress Enterobacteriaceae expansion and restore gut microbiome homeostasis.