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Gut Mucosal Microbiome Is Perturbed in Rheumatoid Arthritis Mice and Partly Restored after TDAG8 Deficiency or Suppression by Salicylanilide Derivative
Authors:Ngoc Tuan Nguyen  Wei-Hsin Sun  Tzu-Hsuan Chen  Po-Chun Tsai  Chih-Chen Chen  Shir-Ly Huang
Affiliation:1.Faculty of Applied Sciences, Ton Duc Thang University, Ho Chi Minh City 700000, Vietnam;2.Department of Life Sciences and Institute of Genome Sciences, National Yang Ming Chiao Tung University, Taipei 112, Taiwan; (W.-H.S.); (T.-H.C.);3.Institute of Microbiology and Immunology, National Yang Ming Chiao Tung University, Taipei 112, Taiwan; (P.-C.T.); (C.-C.C.)
Abstract:Rheumatoid arthritis (RA), an autoimmune disease, is characterized by chronic joint inflammation and pain. We previously found that the deletion of T-cell death-associated gene 8 (TDAG8) significantly reduces disease severity and pain in RA mice. Whether it is by modulating gut microbiota remains unclear. In this study, 64 intestinal samples of feces, cecal content, and cecal mucus from the complete Freund’s adjuvant-induced arthritis mouse models were compared. The α- and β-diversity indices of the microbiome were significantly lower in RA mice. Cecal mucus showed a higher ratio of Firmicutes to Bacteroidetes in RA than healthy mice, suggesting the ratio could serve as an RA indicator. Four core genera, Eubacterium_Ventriosum, Alloprevotella, Rikenella, and Treponema, were reduced in content in both feces and mucus RA samples, and could serve microbial markers representing RA progression. TDAG8 deficiency decreased the abundance of proinflammation-related Eubacterium_Xylanophilum, Clostridia, Ruminococcus, Paraprevotella, and Rikenellaceae, which reduced local mucosal inflammation to relieve RA disease severity and pain. The pharmacological block of the TDAG8 function by a salicylanilide derivative partly restored the RA microbiome to a healthy composition. These findings provide a further understanding of specific bacteria interactions with host gut mucus in the RA model. The modulation by TDAG8 on particular bacteria can facilitate microbiota-based therapy.
Keywords:rheumatoid arthritis  pain  T-cell death-associated gene 8  microbiome  microbial diversity
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