Table_1_Cross-Talk Between Butyric Acid and Gut Microbiota in Ulcerative Colitis Following Fecal Microbiota Transplantation.DOCX

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.

粪便微生物群移植（FMT）能够抑制溃疡性结肠炎（UC）的进展。然而，FMT如何调节肠道微生物群以及哪些生物标志物对于评估FMT疗效具有价值尚不明确。本研究旨在确定FMT治疗UC后肠道微生物群的变化及其与丁酸的关系。从健康个体或小鼠中分离粪便微生物群（FM），并将其移植到12名UC患者或由硫酸葡聚糖（DSS）诱导的结肠炎小鼠体内。监测了他们的临床结肠炎严重程度。通过16S测序和生物信息学分析了他们的肠道微生物群。利用液相色谱-质谱联用（LC-MS）对FMT后复发性症状的5名UC患者和个体小鼠的粪便短链脂肪酸（SCFAs）水平进行了量化。在体外测试了丁酸对肠道微生物群丰富度和多样性的影响。回顾性分析了丁酸产生菌与FMT组合对45名UC患者临床反应的影响。与对照组相比，FMT显著增加了UC患者丁酸产生菌和粪便丁酸水平的丰富度。FMT显著增加了结肠炎小鼠的α多样性，改变了肠道微生物结构，并提高了粪便丁酸水平。与丁酸厌氧培养相比，FMT与含丁酸产生菌的益生菌的组合显著延长了UC的临床缓解期。因此，粪便丁酸水平可能成为评估FMT治疗UC疗效的生物标志物，并且通过改变肠道微生物群，添加丁酸产生菌可能延长FMT对UC的治疗效果。