Prebiotic inulin controls Th17 cells mediated central nervous system autoimmunity through modulating the gut microbiota and short chain fatty acids
Ning Li,
Xinyan Han,
Ming Ruan,
Fei Huang,
Liu Yang,
Tianhao Xu,
Huijun Wang,
Hui Wu,
Songshan Shi,
Yongjun Wang,
Xiaojun Wu,
Shunchun Wang
Affiliations
Ning Li
The MOE Key Laboratory for Standardization of Chinese Medicines and the MOE Innovation Centre for Basic Medicine Research on Qi-Blood TCM Theories, Shanghai Key Laboratory of Compound Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, China
Xinyan Han
The MOE Key Laboratory for Standardization of Chinese Medicines and the MOE Innovation Centre for Basic Medicine Research on Qi-Blood TCM Theories, Shanghai Key Laboratory of Compound Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, China
Ming Ruan
Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
Fei Huang
The MOE Key Laboratory for Standardization of Chinese Medicines and the MOE Innovation Centre for Basic Medicine Research on Qi-Blood TCM Theories, Shanghai Key Laboratory of Compound Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, China
Liu Yang
The MOE Key Laboratory for Standardization of Chinese Medicines and the MOE Innovation Centre for Basic Medicine Research on Qi-Blood TCM Theories, Shanghai Key Laboratory of Compound Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, China
Tianhao Xu
Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
Huijun Wang
The MOE Key Laboratory for Standardization of Chinese Medicines and the MOE Innovation Centre for Basic Medicine Research on Qi-Blood TCM Theories, Shanghai Key Laboratory of Compound Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, China
Hui Wu
The MOE Key Laboratory for Standardization of Chinese Medicines and the MOE Innovation Centre for Basic Medicine Research on Qi-Blood TCM Theories, Shanghai Key Laboratory of Compound Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, China
Songshan Shi
The MOE Key Laboratory for Standardization of Chinese Medicines and the MOE Innovation Centre for Basic Medicine Research on Qi-Blood TCM Theories, Shanghai Key Laboratory of Compound Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, China
Yongjun Wang
Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
Xiaojun Wu
The MOE Key Laboratory for Standardization of Chinese Medicines and the MOE Innovation Centre for Basic Medicine Research on Qi-Blood TCM Theories, Shanghai Key Laboratory of Compound Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, China
Shunchun Wang
The MOE Key Laboratory for Standardization of Chinese Medicines and the MOE Innovation Centre for Basic Medicine Research on Qi-Blood TCM Theories, Shanghai Key Laboratory of Compound Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, China
Multiple sclerosis (MS) is an autoimmune disease characterized by inflammatory demyelination occurring in the central nervous system (CNS). Inulin is a common prebiotic that can improve metabolic disorders by modulating the gut microbiota. However, its capacity to affect CNS autoimmunity is poorly recognized. Experimental autoimmune encephalomyelitis (EAE) is a classical mouse model of MS. Herein, we found that oral administration of inulin ameliorated the severity EAE in mice, accompanied by reductions in inflammatory cell infiltration and demyelination in the CNS. These reductions were associated with decreased proportion and numbers of Th17 cells in brain and spleen. Consistent with the findings, the serum concentrations of IL-17, IL-6, and TNF-α were reduced in inulin treated EAE mice. Moreover, the proliferation of auto-reactive lymphocytes, against MOG35-55 antigen, was attenuated ex vivo. Mechanistically, inulin treatment altered the composition of gut microbiota. It increased Lactobacillus and Dubosiella whereas decreased g_Prevotellaceae_NK3B31_group at the genus level, alongside with elevated concentration of butyric acid in fecal content and serum. In vitro, butyrate, but not inulin, could inhibit the activation of MOG35-55 stimulated lymphocytes. Furthermore, fecal microbiota transplantation assay confirmed that fecal contents of inulin-treated normal mice had an ameliorative effect on EAE mice. In contrast, antibiotic cocktail (ABX) treatment diminished the therapeutic effect of inulin in EAE mice as well as the reduction of Th17 cells, while supplementation with Lactobacillus reuteri restored the amelioration effect. These results confirmed that the attenuation of inulin on Th17 cells and inflammatory demyelination in EAE mice was dependent on its modulation on gut microbiota and metabolites. Our findings provide a potential therapeutic regimen for prebiotic inulin supplementation in patients with multiple sclerosis.
