复发性艰难梭菌感染患者粪便微生物群移植后短链脂肪酸和胆汁酸代谢的恢复

Restoration of short chain fatty acid and bile acid metabolism following fecal microbiota transplantation in patients with recurrent Clostridium difficile infection.

作者信息

Seekatz Anna M, Theriot Casey M, Rao Krishna, Chang Yu-Ming, Freeman Alison E, Kao John Y, Young Vincent B

机构信息

Department of Internal Medicine, Division of Infectious Diseases, University of Michigan Medical School, Ann Arbor, MI, United States.

Department of Internal Medicine, Division of Gastroenterology, University of Michigan Medical School, Ann Arbor, MI, United States.

出版信息

Anaerobe. 2018 Oct;53:64-73. doi: 10.1016/j.anaerobe.2018.04.001. Epub 2018 Apr 12.

Abstract

A significant proportion of individuals develop recurrent Clostridium difficile infection (CDI) following initial disease. Fecal microbiota transplantation (FMT), a highly effective treatment method for recurrent CDI, has been demonstrated to induce microbiota recovery. One of the proposed functions associated with restoration of colonization resistance against C. difficile has been recovery of bile acid metabolism. In this study, we aimed to assess recovery of short chain fatty acids (SCFAs) in addition to bile acids alongside microbial community structure in six patients with recurrent CDI following treatment with FMT over time. Using 16S rRNA gene-based sequencing, we observed marked similarity of the microbiota between recipients following FMT (n = 6, sampling up to 6 months post-FMT) and their respective donors. Sustained increases in the levels of the SCFAs butyrate, acetate, and propionate were observed post-FMT, and variable recovery over time was observed in the secondary bile acids deoxycholate and lithocholate. To correlate these changes with specific microbial taxa at an individual level, we applied a generalized estimating equation approach to model metabolite concentrations with the presence of specific members of the microbiota. Metabolites that increased following FMT were associated with bacteria classified within the Lachnospiraceae, Ruminococcaceae, and unclassified Clostridiales families. In contrast, members of these taxa were inversely associated with primary bile acids. The longitudinal aspect of this study allowed us to characterize individualized patterns of recovery, revealing variability between and within patients following FMT.

摘要

相当一部分个体在初次感染艰难梭菌后会出现复发性感染(CDI)。粪便微生物群移植(FMT)是一种治疗复发性CDI的高效方法,已被证明可促使微生物群恢复。与恢复对艰难梭菌的定植抗性相关的一个假定功能是胆汁酸代谢的恢复。在本研究中,我们旨在评估6例复发性CDI患者在接受FMT治疗后,随着时间推移,除了胆汁酸之外的短链脂肪酸(SCFAs)的恢复情况以及微生物群落结构。使用基于16S rRNA基因的测序技术,我们观察到接受FMT后的受者(n = 6,在FMT后长达6个月进行采样)与其各自供体之间的微生物群具有显著相似性。FMT后观察到短链脂肪酸丁酸、乙酸和丙酸水平持续升高,并且在次级胆汁酸脱氧胆酸和石胆酸中观察到随时间的可变恢复。为了在个体水平上使这些变化与特定微生物分类群相关联,我们应用广义估计方程方法来模拟代谢物浓度与微生物群特定成员的存在情况。FMT后增加的代谢物与分类在毛螺菌科、瘤胃球菌科和未分类的梭菌目科内的细菌相关。相反,这些分类群的成员与初级胆汁酸呈负相关。本研究的纵向研究使我们能够表征个体化的恢复模式,揭示FMT后患者之间和患者内部的变异性。

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