NLRP3 inflammasome partially mediates genotoxic E. coli infection in lean but not in genetically obese mice.

Gut microbiota dysbiosis in inflammatory bowel diseases and metabolic disorders is associated with increased Escherichia coli abundance, a condition exacerbated by a high-fat diet (HFD). However, the metabolic consequences of E. coli infection, particularly in relation to host metabolic state, remain poorly characterized. To this aim, we investigated the impact of commensal, NMEC genotoxic and AIEC proinflammatory E. coli on gut microbiota, inflammation and metabolic markers in wild-type (WT) lean, ob/ob, and HFD-fed WT mice. The gut microbiota of ob/ob mice showed minimal alterations whatever the strain. Only WT lean mice displayed an IL-18-associated genotoxic strain-induced colon inflammation, partially alleviated by NLRP3 inflammasome inhibition, with no significant effect in ob/ob mice. These findings reveal a divergent response to E. coli infection between lean and obese mice, with the potential involvement of NLRP3 inflammasome acting as a moderate regulator of colon inflammation during genotoxic E. coli infection in lean mice.