Department of Medicine, Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Department of Medicine, Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Cell Host Microbe. 2020 Apr 8;27(4):659-670.e5. doi: 10.1016/j.chom.2020.01.021. Epub 2020 Feb 25.
Secondary bile acids (SBAs) are derived from primary bile acids (PBAs) in a process reliant on biosynthetic capabilities possessed by few microbes. To evaluate the role of BAs in intestinal inflammation, we performed metabolomic, microbiome, metagenomic, and transcriptomic profiling of stool from ileal pouches (surgically created resevoirs) in colectomy-treated patients with ulcerative colitis (UC) versus controls (familial adenomatous polyposis [FAP]). We show that relative to FAP, UC pouches have reduced levels of lithocholic acid and deoxycholic acid (normally the most abundant gut SBAs), genes required to convert PBAs to SBAs, and Ruminococcaceae (one of few taxa known to include SBA-producing bacteria). In three murine colitis models, SBA supplementation reduces intestinal inflammation. This anti-inflammatory effect is in part dependent on the TGR5 bile acid receptor. These data suggest that dysbiosis induces SBA deficiency in inflammatory-prone UC patients, which promotes a pro-inflammatory state within the intestine that may be treated by SBA restoration.
次级胆汁酸（SBAs）来源于初级胆汁酸（PBAs），这一过程依赖于少数微生物所具有的生物合成能力。为了评估胆汁酸在肠道炎症中的作用，我们对接受结肠切除术治疗的溃疡性结肠炎（UC）患者与对照（家族性腺瘤性息肉病[FAP]）的回肠袋（手术创建的储液池）粪便进行了代谢组学、微生物组学、宏基因组学和转录组学分析。我们发现，与 FAP 相比，UC 袋中石胆酸和脱氧胆酸（通常是最丰富的肠道 SBAs）的水平降低，将 PBA 转化为 SBA 所需的基因以及毛螺菌科（已知包含产 SBA 细菌的少数分类群之一）减少。在三种小鼠结肠炎模型中，SBA 补充可减轻肠道炎症。这种抗炎作用部分依赖于 TGR5 胆汁酸受体。这些数据表明，肠道菌群失调导致易发生炎症的 UC 患者 SBA 缺乏，从而在肠道内引发促炎状态，SBA 的恢复可能对此种状态进行治疗。
