INSERM ERL U 1057, UMR7203, Paris, France.
Gut. 2013 Apr;62(4):531-9. doi: 10.1136/gutjnl-2012-302578. Epub 2012 Sep 19.
Gut microbiota metabolises bile acids (BA). As dysbiosis has been reported in inflammatory bowel diseases (IBD), we aim to investigate the impact of IBD-associated dysbiosis on BA metabolism and its influence on the epithelial cell inflammation response.
Faecal and serum BA rates, expressed as a proportion of total BA, were assessed by high-performance liquid chromatography tandem mass spectrometry in colonic IBD patients (42) and healthy subjects (29). The faecal microbiota composition was assessed by quantitative real-time PCR. Using BA profiles and microbiota composition, cluster formation between groups was generated by ranking models. The faecal BA profiles in germ-free and conventional mice were compared. Direct enzymatic activities of BA biotransformation were measured in faeces. The impact of BA on the inflammatory response was investigated in vitro using Caco-2 cells stimulated by IL-1β.
IBD-associated dysbiosis was characterised by a decrease in the ratio between Faecalibacterium prausntizii and Escherichia coli. Faecal-conjugated BA rates were significantly higher in active IBD, whereas, secondary BA rates were significantly lower. Interestingly, active IBD patients exhibited higher levels of faecal 3-OH-sulphated BA. The deconjugation, transformation and desulphation activities of the microbiota were impaired in IBD patients. In vitro, secondary BA exerted anti-inflammatory effects, but sulphation of secondary BAs abolished their anti-inflammatory properties.
Impaired microbiota enzymatic activity observed in IBD-associated dysbiosis leads to modifications in the luminal BA pool composition. Altered BA transformation in the gut lumen can erase the anti-inflammatory effects of some BA species on gut epithelial cells and could participate in the chronic inflammation loop of IBD.
肠道微生物群代谢胆汁酸（BA）。由于在炎症性肠病（IBD）中已经报道了菌群失调，我们旨在研究 IBD 相关的菌群失调对 BA 代谢的影响及其对上皮细胞炎症反应的影响。
通过高效液相色谱串联质谱法评估结肠 IBD 患者（42 例）和健康受试者（29 例）的粪便和血清 BA 率，以总 BA 的比例表示。通过定量实时 PCR 评估粪便微生物群组成。使用 BA 谱和微生物群组成，通过排名模型生成组之间的聚类形成。比较无菌和常规小鼠的粪便 BA 谱。在粪便中测量 BA 生物转化的直接酶活性。通过用 IL-1β 刺激 Caco-2 细胞在体外研究 BA 对炎症反应的影响。
IBD 相关的菌群失调的特征是 Faecalibacterium prausntizii 和 Escherichia coli 的比例降低。在活动 IBD 中，粪便结合 BA 率显着升高，而次级 BA 率显着降低。有趣的是，活动 IBD 患者表现出更高水平的粪便 3-OH-硫酸盐 BA。IBD 患者的粪便微生物群去共轭、转化和脱硫活性受损。在体外，次级 BA 发挥抗炎作用，但次级 BA 的硫酸盐化会消除其抗炎特性。
在 IBD 相关的菌群失调中观察到的微生物群酶活性受损导致腔内 BA 池组成发生变化。肠道腔中 BA 的转化改变可能会消除某些 BA 物种对肠道上皮细胞的抗炎作用，并可能参与 IBD 的慢性炎症循环。
