AUTHOR=Zhou Bailing , Dong Chunyan , Zhao Binyan , Lin Ke , Tian Yaomei , Zhang Rui , Zhu Lixin , Xu Hueng , Yang Li 

TITLE=Bacteroides fragilis participates in the therapeutic effect of methotrexate on arthritis through metabolite regulation

JOURNAL=Frontiers in Microbiology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2022.1015130

DOI=10.3389/fmicb.2022.1015130

ISSN=1664-302X

ABSTRACT=<p>Methotrexate (MTX) is a preferred disease-modifying anti-rheumatic drug in the management of rheumatoid arthritis (RA). However, the toxicity and inefficiency of MTX limit its clinical application. Gut microbiota has been implicated in the side effects and efficacy of MTX. In this study, the analysis of the gut microbiota in RA patients revealed that the abundances of intestinal <italic>Bacteroides fragilis</italic> was reduced after MTX treatment. We observed that MTX has no obvious therapeutic effect in the absence of <italic>B. fragilis</italic>, while transplantation of <italic>B. fragilis</italic> restored the efficacy of MTX in antibiotics-pretreated collagen-induced arthritis (CIA) mice. In addition, <italic>B. fragilis</italic> gavage was accompanied by an increase in butyrate. Supplementation of butyrate restored the response to MTX in gut microbiota-deficient mice, to a similar level achieved by <italic>B. fragilis</italic> gavage. These results show that gut microbiota-regulated butyrate plays an essential role in the efficacy of MTX, which will provide new strategies to improve the effectiveness of methotrexate in RA treatment.</p>