Impact of Fecal Microbiota Transplantation on Gut Bacterial Bile Acid Metabolism in Humans.
Impact of Fecal Microbiota Transplantation on Gut Bacterial Bile Acid Metabolism in Humans.
复制标题
作者：
粪便微生物区系移植(FMT)是治疗和预防代谢性疾病的一种有前途的治疗方式。我们之前在肥胖代谢健康的患者中进行了一项双盲、随机、安慰剂对照的FMT试点试验，结果发现，与安慰剂对照组相比，FMT增强了肠道细菌胆汁酸代谢，并延缓了糖耐量受损的发展。因此，我们对从这些患者收集的粪便样本进行了二次分析，以评估FMT改善代谢健康和增加肠道细菌胆汁酸代谢的潜在肠道微生物种类。在基线和FMT或安慰剂治疗4周后收集的粪便样本进行了鸟枪式超基因组分析。采用超高效液-质联用技术对粪便胆汁酸进行分析。与肠道胆汁酸代谢有关的富含FMT的细菌包括脱硫弧菌、费尔菲尔德氏脱硫杆菌和梭状芽胞杆菌。为了确定参与肠道微生物胆汁酸代谢的候选细菌，我们评估了细菌物种丰度和胆汁酸谱之间的相关性，重点是肠道细菌代谢的胆汁酸产物。卵形拟杆菌和多雷对虾与未结合胆汁酸呈正相关。青春型双歧杆菌、产气柯林氏杆菌、普氏杆菌与次生胆汁酸呈正相关。综上所述，这些数据确定了几种可能有助于FMT代谢益处的候选细菌，以及需要进一步功能验证的肠道细菌胆汁酸代谢。
Fecal microbiota transplantation (FMT) is a promising therapeutic modality for the treatment and prevention of metabolic disease. We previously conducted a double-blind, randomized, placebo-controlled pilot trial of FMT in obese metabolically healthy patients in which we found that FMT enhanced gut bacterial bile acid metabolism and delayed the development of impaired glucose tolerance relative to the placebo control group. Therefore, we conducted a secondary analysis of fecal samples collected from these patients to assess the potential gut microbial species contributing to the effect of FMT to improve metabolic health and increase gut bacterial bile acid metabolism. Fecal samples collected at baseline and after 4 weeks of FMT or placebo treatment underwent shotgun metagenomic analysis. Ultra-high-performance liquid chromatography-mass spectrometry was used to profile fecal bile acids. FMT-enriched bacteria that have been implicated in gut bile acid metabolism included Desulfovibrio fairfieldensis and Clostridium hylemonae. To identify candidate bacteria involved in gut microbial bile acid metabolism, we assessed correlations between bacterial species abundance and bile acid profile, with a focus on bile acid products of gut bacterial metabolism. Bacteroides ovatus and Phocaeicola dorei were positively correlated with unconjugated bile acids. Bifidobacterium adolescentis, Collinsella aerofaciens, and Faecalibacterium prausnitzii were positively correlated with secondary bile acids. Together, these data identify several candidate bacteria that may contribute to the metabolic benefits of FMT and gut bacterial bile acid metabolism that requires further functional validation.