Bilophila wadsworthia worsens high-fat diet-induced metabolic impairments in inflammation dependent and independent manners [bacterial gene expression]

Dietary lipids favor the growth of the pathobiont Bilophila wadsworthia, but the relevance of this expansion in metabolic syndrome pathogenesis remains unknown. Here, we showed that B. wadsworthia synergize with HFD to promote higher inflammation, intestinal barrier dysfunction and bile acid dysmetabolism, leading to higher glucose dysmetabolism and hepatic steatosis. Host-microbiota transcriptomics analysis unraveled pathways, particularly butanoate metabolism, which may underlie the metabolic effects mediated by B. wadsworthia. Pharmacological suppression of B. wadsworthia-associated inflammation unmasked the bacterium’s intrinsic capacity to induce a negative impact on glycemic control and hepatic function. Finally, the probiotic Lactobacillus rhamnosus CNCM I-3690 was able to limit B. wadsworthia-induced immune and metabolic impairment by limiting its expansion, reducing inflammation and reinforcing intestinal barrier. Our results support a new avenue for interventions against western diet-driven inflammatory and metabolic diseases. RNA-seq analysis of bacterial RNA to look at abundances of bacterial transcripts in mouse feces of mice subjected to different diets and/or inoculations. ASF = altered Schaedler flora