Role of Gut Microbiota in Rheumatoid Arthritis

Aim Gut microbiota play an important role in rheumatoid arthritis (RA). Biological therapies targeting tumor necrosis factor‐α (TNF‐α) have been used for treatment in RA patients. However, whether TNF‐α antagonist has some influence on gut microbiota is still unknown. This study aims to investigate the distribution of gut microbiota in collagen‐induced arthritis (CIA) mice treated with the TNF‐α antagonist etanercept. Methods Collagen‐induced arthritis mice were induced by type II collagen. Cytokine expression was detected by real‐time polymerase chain reaction. 16S ribosomal RNA sequencing was performed to characterize the gut microbiota in CIA mice treated with vehicle or etanercept. Sequencing reads were processed by Microbial Ecology software program. Results Compared with vehicle‐treated mice, we showed that CIA mice treated with etanercept led to attenuation of inflammation and reduced expression of TNF‐α, interferon (IFN)‐γ, interleukin (IL)‐6 and IL‐21. Meanwhile, results showed operational taxonomic units, richness estimators and the diversity indices of gut microbiota in etanercept‐treated mice were lower than that in vehicle‐treated mice. Moreover, bacterial abundance analyses showed that genus Escherichia/Shigella was more abundant in etanercept‐treated mice, and Lactobacillus, Clostridium XlVa, Tannerella were less abundant. The altered bacterial genus was correlated with TNF‐α, IFN‐γ, IL‐6, IL‐21 and IL‐10. Conclusion Our results revealed that TNF‐α antagonist treatment can reduce the abundance and diversity of gut microbiota in CIA mice. Targeted gut microbiota may be a new therapeutic strategy for the treatment of RA.

The commensal microbiota is one of the environmental triggers of rheumatoid arthritis (RA). Recent studies have identified the characteristics of the gut microbiota in patients with RA. However, it is still unclear how the microbiota can be modulated to slow down disease progression. In the present study, berberine, a modulator of gut microbiota with substantial anti‐RA effect, was chosen to explore the mechanisms by which the microbiota modulators ameliorate RA. The results showed that oral administration of berberine alleviated collagen‐induced arthritis (CIA) in rats in a gut microbiota‐dependent manner. Berberine down‐regulated the diversity and richness of the gut bacteria, reduced the abundance of Prevotella, and elevated the abundance of butyrate‐producing bacteria in CIA rats as determined by the 16S rRNA gene sequence, which might function through limiting the generation of nitrate and stabilizing the physiologic hypoxia in the intestine. Moreover, berberine treatment significantly increased the intestinal butyrate level and promoted the expression and activity of butyryl‐CoA:acetate‐CoA transferase (BUT). The coadministration of a BUT inhibitor largely diminished the adjustment of intestinal environment and the antiarthritic effect of berberine. In conclusion, modulators of the gut microbiota might serve as therapeutic agents for RA by inducing the butyrate generation through promoting the expression and activity of BUT.—Yue, M., Tao, Y., Fang, Y., Lian, X., Zhang, Q., Xia, Y., Wei, Z., Dai, Y. The gut microbiota modulator berberine ameliorates collagen‐induced arthritis in rats by facilitating the generation of butyrate and adjusting the intestinal hypoxia and nitrate supply. FASEB J. 33,12311‐12323 (2019). http://www.fasebj.org

Изучение кишечного микробиома является очень актуальной темой, популярной среди исследователей. По ней проводится большое количество исследований. В настоящее время высокими темпами растет количество данных относительно кишечного микробиома человека как в здоровом состоянии, так и при различных патологических состояниях. С ростом накопленных данных расширяется понимание того, что микробиом является весьма сложной системой, части которой находятся в тесных взаимоотношениях с организмом хозяина, а также реагируют на факторы окружающей среды, в том числе на рацион питания и лекарства. Исследователи находят все больше данных относительно взаимного влияния приема медикаментов, кишечной микрофлоры и внекишечных заболеваний. Cтатья посвящена обзору данных, имеющихся в современной литературе, об особенностях состояния кишечной микрофлоры у больных остеоартритом, ее возможному влиянию на патогенез данного заболевания, а также изменениям, которые возникают в микробиоме на фоне лечения остеоартрита, в частности с помощью нестероидных противовоспалительных препаратов.