Recent advances in the positive role of Clostridium in autoimmune diseases: as a crucial regulator of restoring immune-metabolic equilibrium.

Autoimmune diseases (ADs) are a group of conditions characterized by an overactive immune response that damages one or more organs or tissues of the body. Emerging evidence highlights a critical association between reduced abundance of beneficial Clostridium and the pathogenesis of ADs. Studies show that certain Clostridium, such as Clostridium butyricum (CB) and Faecalibacterium prausnitzii (FP), are almost depleted in multiple ADs. This depletion is associated with impaired immune homeostasis, disrupted intestinal barrier integrity, and heightened inflammation. In diseases such as inflammatory bowel disease (IBD), rheumatoid arthritis (RA), and type 1 diabetes (T1D), restoration of Clostridium species or their metabolites may alleviate disease severity. Mechanistically, Clostridium probiotics may modulate ADs via multiple therapeutic mechanisms, including regulating gut microbiota composition, replenishing beneficial metabolites to restore intestinal barrier integrity, correcting dysregulated immune cell differentiation and homeostasis, and balancing pro- and anti-inflammatory cytokine levels. Our review synthesizes current evidence to delineate the immunomodulatory mechanisms by which Clostridium and its metabolites influence ADs. These findings underscore the therapeutic potential of Clostridium-based interventions in reestablishing immune-metabolic equilibrium in ADs.