OP0009 RESISTANT STARCH INTAKE ALLEVIATES COLLAGEN-INDUCED ARTHRITIS IN MICE BY MODULATING GUT MICROBIOTA AND PROMOTING SCFA PRODUCTION

Abstract

Background Dietary intervention has been an auxiliary therapy in many diseases treatment1. Increasing evidences indicate that dietary compositions vary in their impacts on gut microbial constitution and function capable of affecting the systemic immune status of the host2, 3. Recently, a high fiber diet (HFD) receives close attention due to its effective improvement in symptoms in metabolic diseases and inflammatory diseases. It is also reported that intake of fruits and vegetables can improve the clinical symptoms of rheumatoid arthritis (RA) to a moderate extent. However, it remains unclear how a high fiber diet cross-talks with gut flora and RA initiation or remission. Objectives To systemically evaluate the effect of a high fiber diet mainly composed of resistant starch, a new resource of soluble fiber, on collagen-induced arthritis (CIA) mice and gut microbial composition. Meanwhile, the relative mechanisms was explored in this study. Methods CIA was established by immunization mice with collagen on day 0 and 21. Arthritis severity was evaluated by clinical score, histological staining and micro CT. Fresh stool was collected and gut microbiota analyses were performed by 16s RNA sequencing. Gut barrier dysfuction was evaluated by detecting the genes expression of intestine epithelial tight junction protein Zonulin-1 (ZO-1), Claudin-1 and Occludin. Flow cytometry was applied to measure the proportions of T cell subsets in various immune organs. Short chain fatty acids (SCFA) levels in the circulation and their receptor GPR41, 43 and 109A gene expressions were examined via GC-TOFMS and real-time PCR, respectively. Results High fiber feeding accelerated the arthritis remission in CIA mice, evidenced by the inflammatory cell infiltration reduction in the joints and bone erosion improvement. Th1, 2 and 17 cell population were not affected by HFD. While, regulatory T cell (Treg) percentages in the intestinal lamina propria and spleen were significantly higher in HFD-treated CIA mice, accompanied with an increase of interleukin-10 (IL-10) in the blood. Importantly, HFD modified gut dysbiosis in CIA mice, in particular, promoted the ratio of Bacteroidetes to Firmicutes and the prevalence of Bacteroides acidifaciens. Claudin-1 gene expression in the intestine was significantly increased with the gut flora alteration. Meanwhile, HFD-treated CIA mice had much higher levels of SCFAs in the blood and GPR43 gene expression in the intestine. Blocking SCFAs production by adding hops extract β-acids into drinking water completely eliminated the beneficial effect of HFD on joint swelling, bone erosion and Treg cell expansion in CIA mice. Conclusion Intake of resistant starch drives the significant modifications of the gut microbial composition and SCFAs production capable of triggering Treg cells differentiation and IL-10 production, which favorable to the alleviation of RA.