Protective role of colitis in inflammatory arthritis via propionate-producing Bacteroides in the gut

Front Immunol. 2023 Jan 30:14:1064900. doi: 10.3389/fimmu.2023.1064900. eCollection 2023.

Abstract

Objectives: To investigate whether and how inflammatory disease in the intestine influences the development of arthritis, considering that organ-to-organ communication is associated with many physiological and pathological events.

Methods: First, mice were given drinking water containing dextran sodium sulfate (DSS) and then subjected to inflammatory arthritis. We compared the phenotypic symptoms between the cohoused and separately-housed mice. Next, donor mice were divided into DSS-treated and untreated groups and then cohoused with recipient mice. Arthritis was then induced in the recipients. The fecal microbiome was analyzed by 16S rRNA amplicon sequencing. We obtained type strains of the candidate bacteria and generated propionate-deficient mutant bacteria. Short-chain fatty acids were measured in the bacterial culture supernatant, serum, feces, and cecum contents using gas chromatography-mass spectrometry. Mice fed with candidate and mutant bacteria were subjected to inflammatory arthritis.

Results: Contrary to expectations, the mice treated with DSS exhibited fewer symptoms of inflammatory arthritis. Intriguingly, the gut microbiota contributes, at least in part, to the improvement of colitis-mediated arthritis. Among the altered microorganisms, Bacteroides vulgatus and its higher taxonomic ranks were enriched in the DSS-treated mice. B. vulgatus, B. caccae, and B. thetaiotaomicron exerted anti-arthritic effects. Propionate production deficiency further prevented the protective effect of B. thetaiotaomicron on arthritis.

Conclusions: We suggest a novel relationship between the gut and joints and an important role of the gut microbiota as communicators. Moreover, the propionate-producing Bacteroides species examined in this study may be a potential candidate for developing effective treatments for inflammatory arthritis.

Keywords: Bacteroides; arthritis; colitis; gut microbiota; propionate.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacteria / genetics
  • Bacteroides / genetics
  • Colitis* / pathology
  • Feces / microbiology
  • Mice
  • Propionates* / pharmacology
  • RNA, Ribosomal, 16S / genetics

Substances

  • Propionates
  • RNA, Ribosomal, 16S

Grants and funding

This work was supported by National Research Foundation of Korea grants funded by the Ministry of Science, ICT and Future Planning (Grant 2015R1A3A2032927 to W-UK), the Ministry of Science and ICT (Grant 2022R1A2C1010356 to DK), the Ministry of Education (Grant 2017R1D1A1B04033009 to DK, and 2018R1A6A3A01013428 and 2020R1I1A2069425 to Y-MK), and the Technology Innovation Program funded by the Ministry of Trade, Industry & Energy (MOTIE, Korea; Grant 20013712 to J-YC), and the Liu Inkyung Memorial Endowment Fund and Creative-Pioneering Researchers Program through Seoul National University.