Abstract
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.
Highlights
Acarbose is the prototype of alpha-glucosidase inhibitors and a widely used anti-diabetic drug
We have shown that administration of aglucosidase inhibitors, especially acarbose before arthritis induction has a potent modulatory effect upon reversing joint inflammation both clinically and histologically in collagen-induced arthritis (CIA), but the effect was much less significant when treatment started at the time of arthritis induction
There is evidence suggesting that IL-9 production in T helper-17 (Th17) cells has been related to autoimmune disease including type 1 diabetes (Nowak and Noelle, 2010), asthma (Kearley et al, 2011), and experimental autoimmune encephalomyelitis (Li et al, 2010)
Summary
Acarbose is the prototype of alpha-glucosidase inhibitors and a widely used anti-diabetic drug. Acarbose is primarily prescribed to patients with type 2 diabetes as monotherapy or as add-on to other antidiabetic drug treatment (Joshi et al, 2015), especially in those with poorly controlled blood glucose by other antidiabetic drugs. Additional benefits have been noticed in diabetic patients treated with acarbose such as reduced risk for myocardial infarction and improved lipid profile and reduced levels of inflammatory cytokines in peripheral blood (Hanefeld and Schaper, 2008; Joshi et al, 2015; Su et al, 2015). The anti-inflammatory effect of acarbose has been experimentally proven in two mouse models of inflammation, namely collagen-induced arthritis (CIA) and a psoriasis model (Chen et al, 2015; Chen et al, 2016). In the two models of inflammatory diseases, daily administration of acarbose attenuated the diseases severity
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