Intestinal barrier dysfunction plays an integral role in arthritis pathology and can be targeted to ameliorate disease
Diana E. Matei, Madhvi Menon, Dagmar Alber, Andrew Smith, Bahman Nedjat-Shokouhi, Alessio Fasano, L Magill, Amanda Duhlin, Samuel Bitoun, Aude Gleizes, Salima Hacein‐Bey‐Abina, Jessica Manson, Elizabeth C. Rosser, Nigel Klein, Paul A. Blair, Claudia Mauri
Abstract
BACKGROUND: Evidence suggests an important role for gut-microbiota dysbiosis in the development of rheumatoid arthritis (RA). The link between changes in gut bacteria and the development of joint inflammation is missing. Here, we address whether there are changes to the gut environment and how they contribute to arthritis pathogenesis. METHODS: We analyzed changes in markers of gut permeability, damage, and inflammation in peripheral blood and serum of RA patients. Serum, intestines, and lymphoid organs isolated from K/BxN mice with spontaneous arthritis or from wild-type, genetically modified interleukin (IL)-10R FINDINGS: RA patients display increased levels of serum markers of gut permeability and CONCLUSIONS: We suggest that breakdown of gut-barrier integrity contributes to arthritis development and propose restoration of gut-barrier homeostasis as a new therapeutic approach for RA. FUNDING: Funded by Versus Arthritis (21140 and 21257) and UKRI/MRC (MR/T000910/1).