Bilophila wadsworthia worsens high-fat diet-induced metabolic impairments in inflammation dependent and independent manners [mouse gene expression]. Bilophila wadsworthia worsens high-fat diet-induced metabolic impairments in inflammation dependent and independent manners [mouse 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. Overall design: Microarray analysis was performed by using total tissue from caecum tip of mice on week 5 post-treatment.

膳食脂质可促进致病共生菌（pathobiont）沃氏嗜胆菌（Bilophila wadsworthia）的增殖，但该菌的扩增在代谢综合征发病机制中的相关性仍尚不明确。本研究显示，沃氏嗜胆菌可与高脂饮食（High Fat Diet, HFD）协同作用，加剧炎症反应、肠道屏障功能障碍与胆汁酸代谢紊乱，进而引发更严重的糖代谢异常与肝脂肪变性。宿主-菌群转录组学分析揭示了多条通路，尤其是丁酸代谢（butanoate metabolism）通路，可能是沃氏嗜胆菌介导代谢效应的潜在机制。通过药理学手段抑制沃氏嗜胆菌相关炎症，可揭示该菌自身具备诱导血糖调控异常与肝功能损伤的固有能力。最后，本研究发现益生菌鼠李糖乳杆菌（Lactobacillus rhamnosus）CNCM I-3690可通过抑制沃氏嗜胆菌的增殖、减轻炎症反应并强化肠道屏障功能，从而缓解该菌诱导的免疫与代谢损伤。本研究结果为针对西式饮食诱导的炎症性与代谢性疾病的干预策略提供了全新方向。实验整体设计：于小鼠接受处理后第5周，提取其盲肠尖端的总组织，开展微阵列（microarray）分析。