ena-STUDY-Unit INSERM 1157/UMR 7203-05-03-2018-10:40:01:425-2221
Bilophila wadsworthia worsens high-fat diet-induced metabolic impairments in inflammation dependent and independent manners.
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. HFD had been consistently shown to modulate intestinal microbial community; thus, we evaluated the global microbiota changes induced by the HFD diet as well as the microbiota effect of inoculating the mice with B. wadsworthia and L. rhamnosus CNCM I-3690 using 16s rRNA-based high throughput sequencing technique. HFD has a significant impact on microbiota composition but the effect of B. wadsworthia and L. rhamnosus CNCM I-3690 on the microbiota composition was limited and may be more relevant at the metabolic functional level. 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.
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. HFD had been consistently shown to modulate intestinal microbial community; thus, we evaluated the global microbiota changes induced by the HFD diet as well as the microbiota effect of inoculating the mice with B. wadsworthia and L. rhamnosus CNCM I-3690 using 16s rRNA-based high throughput sequencing technique. HFD has a significant impact on microbiota composition but the effect of B. wadsworthia and L. rhamnosus CNCM I-3690 on the microbiota composition was limited and may be more relevant at the metabolic functional level. 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.