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Alpha-Glucosidase Inhibitors Alter Gut Microbiota and Ameliorate Collagen-Induced Arthritis.

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机构: [1]Division of Arthritis and Rheumatic Diseases, Oregon Health & Science University, Portland, OR, United States, [2]Department of Rheumatology, West China Hospital, Sichuan University, Chengdu, China, [3]Section of Rheumatology, VA Portland Health Care System, Portland, OR, United States, [4]Casey Eye Institute, Oregon Health & Science University, Portland, OR, United States, [5]Department of Medical Informatics and Clinical Epidemiology, Oregon Health & Science University, Portland, OR, United States, [6]Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, United States, [7]Department of Rheumatology, The First Hospital, Guangzhou University of Chinese Medicine, Guangzhou, China
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关键词: acarbose arthritis (including rheumatoid arthritis) microbiome Th17 Treg cells

摘要:
Acarose is an anti-diabetic drug and exhibits anti-arthritic effects. We hypothesized that acarbose influences the gut microbiota to affect the course of arthritis and tested this hypothesis in a collagen-induced arthritis (CIA) murine model. Acarbose in drinking water was administered via gastric gavage started prior to or at the time of CIA induction. Gut microbiota were evaluated with 16S rRNA gene sequencing from fecal pellets collected prior to arthritis induction, during onset of arthritis, and after treatment. Immune response was evaluated by measuring changes in T helper-17 (Th17) and T regulatory (Treg) cells in the spleen and intestine, as well as serum cytokine levels. Before induction of CIA, acarbose significantly reduced the incidence of arthritis and attenuated clinical severity of arthritis. The frequency of Th17 cells was significantly decreased in the intestinal lamina propria in acarbose treated mice. Mice that were treated with acarbose showed significantly increased CD4+CD25+Foxp3+ Treg cells with elevation of Helios and CCR6. A remarkable alteration in microbial community was observed in acarbose treated mice. Bacterial diversity and richness in mice with arthritis were significantly lower than those in acarbose treated groups. The frequency of Firmicutes was significantly reduced after arthritis onset but was restored after treatment with acarbose. The frequency of Lactobacillus, Anaeroplasma, Adlercreutzia, RF39 and Corynebacterium was significantly higher in control groups than in acarbose treated, while Oscillospira, Desulfovibrio and Ruminococcus enriched in acarbose treated group. Miglitol, another α-glucosidase inhibitor showed a similar but less potent anti-arthritic effect to that of acarbose. These data demonstrate that acarbose alleviated CIA through regulation of Th17/Treg cells in the intestinal mucosal immunity, which may have resulted from the impact of acarbose on gut microbial community. Inexpensive antidiabetic drugs with an excellent safety profile are potentially useful for managing rheumatoid arthritis. Copyright © 2020 Zhang, Song, Zhang, Metea, Schleisman, Karstens, Leung, Zhang, Xu, Liu, Asquith and Chu.

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出版当年[2019]版:
大类 | 2 区 医学
小类 | 2 区 药学
最新[2023]版:
大类 | 2 区 医学
小类 | 2 区 药学
第一作者:
第一作者机构: [1]Division of Arthritis and Rheumatic Diseases, Oregon Health & Science University, Portland, OR, United States, [2]Department of Rheumatology, West China Hospital, Sichuan University, Chengdu, China, [3]Section of Rheumatology, VA Portland Health Care System, Portland, OR, United States,
通讯作者:
通讯机构: [1]Division of Arthritis and Rheumatic Diseases, Oregon Health & Science University, Portland, OR, United States, [3]Section of Rheumatology, VA Portland Health Care System, Portland, OR, United States,
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