Cross-Talk Between Butyric Acid and Gut Microbiota in Ulcerative Colitis Following Fecal Microbiota Transplantation.

Hao-Ming Xu,Jie He,Yu-Qiang Nie,Chong Zhao,Wen-Qi Huang,Jing Xu,Yao Peng,You-Lian Zhou,Yong-Jian Zhou,Hai-Lan Zhao,Hong-Li Huang,Chuang-Yu Cao

doi:10.3389/fmicb.2021.658292

Abstract

Fecal microbiota transplantation (FMT) can inhibit the progression of ulcerative colitis (UC). However, how FMT modulates the gut microbiota and which biomarker is valuable for evaluating the efficacy of FMT have not been clarified. This study aimed to determine the changes in the gut microbiota and their relationship with butyric acid following FMT for UC. Fecal microbiota (FM) was isolated from healthy individuals or mice and transplanted into 12 UC patients or colitis mice induced by dextran sulfate sodium (DSS). Their clinical colitis severities were monitored. Their gut microbiota were analyzed by 16S sequencing and bioinformatics. The levels of fecal short-chain fatty acids (SCFAs) from five UC patients with recurrent symptoms after FMT and individual mice were quantified by liquid chromatography–mass spectrometry (LC–MS). The impact of butyric acid on the abundance and diversity of the gut microbiota was tested in vitro. The effect of the combination of butyric acid-producing bacterium and FMT on the clinical responses of 45 UC patients was retrospectively analyzed. Compared with that in the controls, the FMT significantly increased the abundance of butyric acid-producing bacteria and fecal butyric acid levels in UC patients. The FMT significantly increased the α-diversity, changed gut microbial structure, and elevated fecal butyric acid levels in colitis mice. Anaerobic culture with butyrate significantly increased the α-diversity of the gut microbiota from colitis mice and changed their structure. FMT combination with Clostridium butyricum-containing probiotics significantly prolonged the UC remission in the clinic. Therefore, fecal butyric acid level may be a biomarker for evaluating the efficacy of FMT for UC, and addition of butyrate-producing bacteria may prolong the therapeutic effect of FMT on UC by changing the gut microbiota.

Highlights

MATERIALS AND METHODSUlcerative colitis (UC) is a heterogeneous, chronic and inflammatory disease
Our data suggest that fecal butyric acid level may be a biomarker for evaluating the efficacy of Fecal microbiota transplantation (FMT) for ulcerative colitis (UC) and addition of butyrate-producing bacteria may prolong the therapeutic effect of FMT on UC by changing the gut microbiota
To understand the mechanisms underlying the action of FMT, 12 UC patients were transplanted with Fecal microbiota (FM) from a healthy donor, and their fecal samples were collected longitudinally

Summary

Introduction

MATERIALS AND METHODSUlcerative colitis (UC) is a heterogeneous, chronic and inflammatory disease. Fecal microbiota transplantation (FMT) is an emerging novel therapy for UC. The FMT procedure includes isolating fecal microbiota (FM) from healthy donors and transplanting into the patient’s gastrointestinal tract to reconstruct the gut microbiota and restore microbial homeostasis (Antushevich, 2020). FMT targets gut microbiome dysbiosis, and despite its unappealing nature, FMT has been demonstrated to induce remission of moderate–severe active UC in humans (Cui et al, 2015; Lai et al, 2019; Chen et al, 2020). FMT can maintain long-term remission in some UC patients (Sood et al, 2019). Further discovery of new biomarkers for evaluating the efficacy of FMT therapy for UC patients and modification of FMT to achieve long-term therapeutic efficacy will be of high significance

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