TNF and rheumatoid arthritis: It was also concluded that butyrate-producing Subdoligranulum variabile ameliorates RA, since this bacterium promotes the expression of tumour necrosis factor-inducible gene 6 protein (TSG-6) after co-culturing with joint cells such as HC and HFLS-RA in vitro, along with the down-regulation of the pro-inflammatory cytokine TNF-α in HFLS-RA, a key player in the pathogenesis of RA, thereby reducing RA inflammation [113].