A black spot gut microbiota facilitates systemic sepsis by TRL4-dependent hyperinflammation

This project investigates how the gut bacterial family Muribaculaceae particularly Sangeribacter muris KT1 3 aggravates systemic sepsis through TLR4 dependent hyperinflammation. Using murine models fecal microbiota transplantation and single cell transcriptomics we show that Muribaculaceae enrichment primes macrophages toward a preactivated inflammatory state resulting in excessive cytokine production and sepsis lethality upon Acinetobacter baumannii infection. Mechanistically Sangeribacter muris secretes heat stable metabolites smaller than three kilodaltons that synergize with pathogen derived LPS to amplify NF kappa B and AP 1 signaling. These findings reveal commensal derived proinflammatory metabolites as key determinants of systemic immune tone and infection outcomes.