Targeted intestinal ROS scavenging alleviated rheumatoid arthritis by microbial metabolite kynurenic acid mediated Treg/Th17 balance through AhR pathway activation.

Authors

Zhiguo Ling, Tingwen Xiang, Chuan Yang, Dongyang Zhang, Yanghao You, Shiyu Xiao, Langlang Xie, Jiulin Tan, Qijie Dai, Gang Huang, Dong Sun, Fei Luo, Yueqi Chen

Published in

Gut microbes. Volume 18. Issue 1. Pages 2739669. Dec 31, 2026. Epub Oct 17, 2026.

Abstract

Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by immune dysregulation, which is often closely related to impaired gut microbiota homeostasis. Excessive reactive oxygen species (ROS) are recognized as critical drivers of microecological immunity disturbance, contributing directly to the inflammatory cascade. However, the underlying mechanism remains unclear. Here, we have used ROS scavengers to alleviate RA progression via inhibiting intestinal ROS and modulating gut microbial kynurenic acid metabolism. Black phosphorus nanosheets (BPNSs), as effective ROS scavengers, significantly ameliorated disease severity in collagen-induced arthritis (CIA) mice by oral administration to eliminate intestinal excess ROS. BPNSs selectively reshaped the gut microbiota and altered its metabolic profile, elevating the relative abundance of the tryptophan-derived metabolite kynurenic acid (KYNA). Mechanistically, elevated KYNA activated the aryl hydrocarbon receptor (AhR) pathway in naïve CD4⁺ T cells, promoting their differentiation into Treg cells through the inhibition of AKT/mTOR signaling pathway. The therapeutic effect of KYNA was further corroborated in CIA mice, where its administration maintained Treg/Th17 balance, attenuated arthritis progression, and enhanced intestinal barrier integrity. These findings elucidate novel gut-immune-bone axis wherein scavenging intestinal ROS drives KYNA mediated AhR-dependent Treg cell differentiation, thereby proposing a promising ROS scavenging-based strategy for RA treatment.

PMID:
42888947
Bibliographic data and abstract were imported from PubMed on 17 Oct 2026.

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