Metabolites from specific intestinal bacteria in vivo fermenting Lycium barbarum polysaccharide improve collagenous arthritis in rats

Rheumatoid arthritis (RA) is an autoimmune disease affected patients' quality of life severely. Our previous study found Lycium barbarum polysaccharide (LBP) alleviated RA, but it remains unknown whether gut microbiota is necessary for the alleviation. Here, RA models were established in rats with microbiota and rats treated by antibiotic cocktail, and LBP was applied for the intervention on rats. The biochemical test, 16S rDNA sequencing and metabolome analysis were applied to analyze the effects of LBP on gut microbiota, their metabolites and hosts. Results showed the LBP intervention improved RA by inhibiting pro-inflammatory cytokines IL-1 alpha, IL-1 beta, TNF-alpha and IL-6 only in rats with microbiota, but not in pseudo-germ-free rats. The abundance of specific bacteria, including Romboutsia, Lactobacillus, Turicibacter, Clostridium_sensu_stricto_1, Faecalibacterium and Adlercreutzia, and several metabolites, including O-desmethylangolensin, 3-hydroxydodecanedioic acid, N-formyl-L-methio-nine, suberic acid, (S)-oleuropeic acid, prolyl-histidine, 13,14-dihydro PGF-1a, (R)-pelletierine and short-chain fatty acids increased only in RA rats with microbiota after the intervention. Our results suggest that intestinal bacteria are necessary for LBP alleviating RA alleviation. The fermentation metabolite acts on the host instead of LBP itself, which may be the reason for the improvement of RA.