Lycium barbarum Polysaccharides-enriched extract Ameliorate Rheumatoid Arthritis via Gut microbiota-mediated regulation of the Tfh/B cell axis.

BACKGROUND

Gut microbiota dysbiosis is implicated in rheumatoid arthritis (RA). While Lycium barbarum polysaccharide-enriched extract (LBP) is known for its anti-inflammatory and immunoregulatory effects, the precise microbial drivers and underlying mechanisms, including their connection to the T follicular helper (Tfh) cell/B cell axis, remain poorly defined.

PURPOSE: The aim of this research is to investigate changes in the gut microbiota of RA patients and CIA rats, and to evaluate whether LBP improves RA by modulating the gut microbiota.

METHOD: Gut microbiota composition was assessed via 16S rRNA gene sequencing in both RA patients and CIA rats. To investigate the mechanisms underlying the therapeutic effect of LBP, flow cytometry, ELISA, and hematoxylin-eosin (HE) staining were employed.

RESULTS

In RA patients, gut microbiota α-diversity was significantly reduced, coupled with decreased levels of Ligilactobacillus and Escherichia-Shigella and an increase in Blautia. In the CIA rat model, LBP treatment counteracted the observed microbiota shifts by increasing the diminished abundances of Ligilactobacillus and Limosilactobacillus and reducing the elevated abundance of Blautia. Specifically, LBP reduced the proportions of splenic Tfh and B cells and lowered serum levels of IgG, IL-6, and IL-21. It also diminished inflammatory infiltration and synovial hyperplasia in joint tissues and repaired colonic crypt architecture.

CONCLUSION

Dysbiosis of the gut microbiota and abnormal activation of Tfh cells may play an essential role in the development and progression of RA. In both human patients and the CIA rats model, Ligilactobacillus and Blautia have been associated with RA pathological processes. LBP may suppress the excessive proliferation of Tfh cells and the subsequent abnormal differentiation of B cells. It is noteworthy that alterations in these key bacterial genera may be linked to the regulation of Tfh cell overactivation and aberrant humoral immune responses.