Background/Purpose: Acarbose, an alpha-glucosidase inhibitor anti-diabetic drug exhibited anti-arthritic effects. The mechanism that acarbose exerts its anti-arthritic effects is not fully understood. Since > 90% of acarbose is not absorbed, we hypothesized that acarbose influences the gut microbiota that affects the course of arthritis. We tested this hypothesis in a collagen-induced arthritis (CIA) model.

Methods: CIA was induced by intradermal injection of chicken collagen type II (CII) emulsified in complete Freund’s adjuvant in male DBA/1 mice. Acarbose, miglitol (a control drug) in drinking water were administered daily at 500 mg/kg via oral gavage. In the prophylactic regimen, mice were treated 7 days prior to the induction of CIA, and in the therapeutic regimen, mice were treated on the day of immunization. All mice were euthanized on day 55 after immunization. Fecal pellets were collected before immunization, during onset of arthritis and after treatment for identification of bacteria using16S rDNA sequencing. Intestines and spleen were harvested for isolation of lymphocytes and analysis for changes of Th17 and Treg cells. Serum was obtained for analysis of cytokines and autoantibodies to CII.

Results: Adminstration before induction of CIA, acarbose significantly reduced the incidence of arthritis and attenuated clinical severity of arthritis. This was accompanied by a significant reduction of levels of anti-CII antibodies compared to those of drinking water treated or miglitol treated groups of mice (P < 0.05). The frequency of Th17 cells was significantly decreased in the intestinal lamina propria in both acarbose and miglitol prophylactic treatment (P < 0.001). Prophylactically treated mice with acarbose showed significantly increased CD4⁺CD25⁺Foxp3⁺ Treg cells (P < 0.01) with elevation of Helios⁺ (P < 0.01) and CCR6⁺ (P < 0.05). Mice prophylactically treated with miglitol also showed an increase of CD4⁺CD25⁺Foxp3⁺ Treg cells (P < 0.01) with increased CCR6⁺ (P < 0.05) in the mucosal sites. Furthermore, a remarkable alteration in microbial community was observed in both acarbose and miglitol treated mice. Bacterial diversity and richness in mice with arthritis were significantly lower than those in acarbose treated groups (P < 0.05). 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 or mitiligol treated, while Oscillospira, Desulfovibrio and Ruminococcus enriched in acarbose or mitiligol treated groups.

Conclusion: These data demonstrated that alpha-glucosidase inhibitors, in particular acarbose alleviated CIA. The therapeutic effect was through regulation of Th17/Treg cells in the intestinal mucosal immunity which might be resulted from impact of these drugs on gut microbial community. These inexpensive antidiabetic drugs with an excellent safety profile are potentially useful for management of rheumatoid arthritis.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/alpha-glucosidase-inhibitors-alter-gut-microbiota-and-ameliorate-collagen-induced-arthritis/