<i>Lactiplantibacillus plantarum</i> fermented hemp (<i>Cannabis sativa</i>) seeds modulate the gut microbiota and metabolic pathways to alleviate autoimmune inflammation in collagen-induced arthritis mice

Rheumatoid arthritis (RA) is a debilitating autoimmune disease that severely affects patients' quality of life. Growing evidence links the gut microbiota, metabolism, and immune regulation to RA, driving interest in gut-targeted therapies. This study evaluates the therapeutic potential of <i>Lactiplantibacillus plantarum</i>-fermented hemp seeds (FHS) in collagen-induced arthritis (CIA) mouse models. FHS intervention significantly reduced joint swelling, cartilage and synovial damage, and systemic inflammation while restoring mobility and balancing CD4⁺ T cell differentiation. Compared to <i>L. plantarum</i> alone, FHS demonstrated superior efficacy. Additionally, FHS modulated RA-associated gut bacteria, including <i>Clostridium disporicum</i>, <i>Duncaniella dubosii</i>, <i>Eisenbergiella massiliensis</i>, <i>Waltera intestinalis</i>, and <i>Muribaculum gordoncarteri</i>, while restoring RA-suppressed species like <i>Akkermansia muciniphila</i>, <i>Konateibacter massiliensis</i>, <i>Lactobacillus johnsonii</i>, <i>Ruminococcus champanellensis</i>, and <i>Phocaeicola vulgatus</i>. FHS also influenced key metabolites, such as short-chain fatty acids, stearic acid, oleic acid, taurine, palmitic acid, docosahexaenoic acid, linoleic acid, and L-tyrosine, impacting metabolic pathways linked to RA progression. Notably, indolelactic acid, homovanillic acid, and bioactive peptides in FHS were absorbed into the bloodstream, exerting direct anti-inflammatory effects. These findings underscore FHS's potential as a therapeutic functional ingredient for RA, offering insights into its mechanisms through gut microbiota modulation and metabolic regulation.