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

Gut microbiota α-diversity was significantly reduced in RA patients compared to healthy controls.

• Assessment was performed via 16S rRNA gene sequencing in RA patients.
• Reduced α-diversity was accompanied by decreased levels of Ligilactobacillus and Escherichia-Shigella.
• An increase in Blautia was observed in RA patients.
• Both Ligilactobacillus and Blautia were identified as associated with RA pathological processes in human patients.

CIA rat model recapitulated key gut microbiota shifts observed in RA patients, including changes in Ligilactobacillus and Blautia.

• 16S rRNA gene sequencing was used to assess gut microbiota composition in CIA rats.
• CIA rats showed diminished abundances of Ligilactobacillus and Limosilactobacillus.
• Elevated abundance of Blautia was observed in CIA rats, mirroring findings in human RA patients.
• Blautia and Ligilactobacillus were consistently associated with RA pathological processes across both human and rat models.

LBP treatment counteracted gut microbiota dysbiosis in CIA rats by restoring key bacterial genera.

• LBP increased the diminished abundances of Ligilactobacillus and Limosilactobacillus in CIA rats.
• LBP reduced the elevated abundance of Blautia in CIA rats.
• LBP also repaired colonic crypt architecture, indicating restoration of gut structural integrity.
• Gut microbiota composition was assessed via 16S rRNA gene sequencing.

LBP reduced the proportions of splenic Tfh and B cells in CIA rats.

• Flow cytometry was employed to assess splenic Tfh and B cell proportions.
• LBP suppressed excessive proliferation of Tfh cells and subsequent abnormal differentiation of B cells.
• Alterations in key bacterial genera (Ligilactobacillus and Blautia) were linked to the regulation of Tfh cell overactivation and aberrant humoral immune responses.

LBP lowered serum levels of IgG, IL-6, and IL-21 in CIA rats.

• ELISA was used to measure serum IgG, IL-6, and IL-21 levels.
• Reductions in these biomarkers indicate suppression of aberrant humoral immune responses.
• IL-21 and IL-6 are cytokines associated with Tfh cell activity and B cell differentiation.
• These findings are consistent with LBP's proposed mechanism of suppressing the Tfh/B cell axis.

LBP diminished inflammatory infiltration and synovial hyperplasia in joint tissues of CIA rats.

• Hematoxylin-eosin (HE) staining was used to assess joint tissue histopathology.
• Reduced inflammatory infiltration and synovial hyperplasia were observed following LBP treatment.
• These histological improvements are consistent with LBP's anti-inflammatory and immunoregulatory effects.

Dysbiosis of the gut microbiota and abnormal activation of Tfh cells were identified as playing an essential role in the development and progression of RA.

• Evidence was gathered from both RA patient samples and the CIA rat model.
• The Tfh/B cell axis was highlighted as a key immunological pathway dysregulated in RA.
• Alterations in Ligilactobacillus and Blautia were linked to regulation of Tfh cell overactivation and aberrant humoral immune responses.
• LBP's therapeutic mechanism was proposed to involve gut microbiota-mediated regulation of this axis.