Alteration of the gut microbiota in tumor necrosis factor‐α antagonist‐treated collagen‐induced arthritis mice

Abstract

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.

Crossing the barriers: Revisiting the gut feeling in rheumatoid arthritis

“…Thus, this observation suggests a beneficial role of Etanercept on microbiota of RA patients [55]. Notably, in a recent study, Wang and colleagues showed an increase of Escherichia/Shigella species in the microbiota of collagen‐induced arthritis (CIA) mice, after treatment with Etanercept [56]. In the same study, the authors found a correlation between Escherichia/Shigella abundance and the decrease of proinflammatory cytokines, such as TNF‐alpha, IFN‐gamma, IL‐6, and IL‐21.…”

“…In the same study, the authors found a correlation between Escherichia/Shigella abundance and the decrease of proinflammatory cytokines, such as TNF‐alpha, IFN‐gamma, IL‐6, and IL‐21. The same bacterial species were associated with the upregulation of the anti‐inflammatory cytokine IL‐10 [56]. In a recent interesting review, Scher and colleagues paid attention to the biotransformation that the gut microbiome operates on several drugs used to treat inflammatory arthritis, with consequent influence on therapeutic response [57].…”

Sustained Drug Treatment Alters the Gut Microbiota in Rheumatoid Arthritis

“…( 11 ) showed that the tumor necrosis factor alpha (TNF-α) inhibitor etanercept can alter microbial communities and at least partially improve the microbiota in RA patients. Similarly, in mice with collagen-induced arthritis, etanercept reduced the abundance of Escherichia/Shigella and increased the abundance of Lactobacillus, Clostridium XIVa , and Tannerella ( 12 ). Additionally, antibiotic-induced partial depletion of the gut microbiota aggravated arthritis symptoms in a RA mouse model ( 13 ).…”

Fecal Microbiota Transplantation Modulates Renal Phenotype in the Humanized Mouse Model of IgA Nephropathy

“…This bidirectional evidence remains stable also evaluating different studies on mice. In some cases, Lachnospiraceae were found increased in a subset of mice showing increased levels of TNFα ( 88 ), meanwhile in another trial the Clostridium cluster XIVa (i.e., Lachnospiraceae ) showed a negative correlation with TNFα ( 89 ). In light of these findings, it is possible to speculate that the influence of microbes on inflammatory state and on inflammatory markers, including TNFα, needs to be evaluated analyzing the deeper taxonomic levels (i.e., species or strain level) rather than the highest ones (e.g., phylum or family level).…”