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. 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体（pathobiont）沃氏嗜胆菌（Bilophila wadsworthia）的增殖，但该菌的扩增在代谢综合征（metabolic syndrome）发病机制中的关联仍尚不明确。本研究证实，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紊乱与肝脂肪变性。通过宿主-微生物组转录组学分析，本研究揭示了可能介导沃氏嗜胆菌代谢效应的潜在通路，其中丁酸代谢通路尤为关键。针对沃氏嗜胆菌相关炎症的药物抑制实验，进一步明确了该菌本身即可对血糖控制与肝功能产生负面影响的内在能力。最后，益生菌鼠李糖乳杆菌（Lactobacillus rhamnosus）CNCM I-3690可通过限制沃氏嗜胆菌的增殖、减轻炎症反应并增强肠屏障功能，从而缓解其诱导的免疫与代谢损伤。本研究结果为针对西式饮食驱动的炎症性与代谢性疾病的干预策略提供了全新方向。本研究采用基因芯片（microarray）技术，对治疗后第5周小鼠盲肠尖端的总组织样本进行了分析。