Department of Soil, Water, and Climate and The BioTechnology Institute, University of Minnesota, St. Paul, Minnesota;
Am J Physiol Gastrointest Liver Physiol. 2014 Feb 15;306(4):G310-9. doi: 10.1152/ajpgi.00282.2013. Epub 2013 Nov 27.
Fecal microbiota transplantation (FMT) has emerged as a highly effective therapy for refractory, recurrent Clostridium difficile infection (CDI), which develops following antibiotic treatments. Intestinal microbiota play a critical role in the metabolism of bile acids in the colon, which in turn have major effects on the lifecycle of C. difficile bacteria. We hypothesized that fecal bile acid composition is altered in patients with recurrent CDI and that FMT results in its normalization. General metabolomics and targeted bile acid analyses were performed on fecal extracts from patients with recurrent CDI treated with FMT and their donors. In addition, 16S rRNA gene sequencing was used to determine the bacterial composition of pre- and post-FMT fecal samples. Taxonomic bacterial composition of fecal samples from FMT recipients showed rapid change and became similar to the donor after the procedure. Pre-FMT fecal samples contained high concentrations of primary bile acids and bile salts, while secondary bile acids were nearly undetectable. In contrast, post-FMT fecal samples contained mostly secondary bile acids, as did non-CDI donor samples. Therefore, our analysis showed that FMT resulted in normalization of fecal bacterial community structure and metabolic composition. Importantly, metabolism of bile salts and primary bile acids to secondary bile acids is disrupted in patients with recurrent CDI, and FMT corrects this abnormality. Since individual bile salts and bile acids have pro-germinant and inhibitory activities, the changes suggest that correction of bile acid metabolism is likely a major mechanism by which FMT results in a cure and prevents recurrence of CDI.
粪便微生物群移植(FMT)已成为治疗抗生素治疗后发生的难治性、复发性艰难梭菌感染(CDI)的一种非常有效的疗法。肠道微生物群在结肠胆汁酸代谢中起着关键作用,而胆汁酸反过来又对艰难梭菌细菌的生命周期有重大影响。我们假设复发性 CDI 患者的粪便胆汁酸组成发生改变,并且 FMT 使其正常化。对接受 FMT 治疗的复发性 CDI 患者及其供体的粪便提取物进行了常规代谢组学和靶向胆汁酸分析。此外,还使用 16S rRNA 基因测序来确定 FMT 前后粪便样本的细菌组成。FMT 受者粪便样本的分类细菌组成迅速变化,并在该过程后变得与供体相似。FMT 前粪便样本含有高浓度的初级胆汁酸和胆盐,而次级胆汁酸几乎无法检测到。相比之下,FMT 后粪便样本主要含有次级胆汁酸,非 CDI 供体样本也是如此。因此,我们的分析表明 FMT 导致粪便细菌群落结构和代谢组成正常化。重要的是,复发性 CDI 患者的胆汁盐和初级胆汁酸向次级胆汁酸的代谢被破坏,而 FMT 纠正了这种异常。由于个体胆汁盐和胆汁酸具有促发芽和抑制活性,这些变化表明胆汁酸代谢的纠正可能是 FMT 导致治愈和预防 CDI 复发的主要机制。