Cinnamaldehyde Attenuates Collagen‐Induced Arthritis in Rats Through Immunomodulation and Alteration of Intestinal Flora Homeostasis and Repair of Intestinal Barrier Damage

ABSTRACT Rheumatoid arthritis (RA) is a complex autoimmune disease, the present study aimed to investigate the effects of cinnamaldehyde (CA) on collagen‐induced arthritis (CIA) in rats, with particular attention to changes in intestinal barrier‐related features, gut microbiota composition, and fecal short‐chain fatty acids (SCFAs). In CIA rats, CA treatment alleviated arthritis‐related signs, reduced inflammatory responses, and attenuated joint pathological damage. CA administration was also associated with restoration of intestinal barrier‐related features, including restoration of colonic histopathology and mucus layer integrity, as well as increased expression of tight junction proteins. Moreover, CA treatment was associated with altered gut microbiota composition. At the genus level, CA intervention was associated with increased abundance of Akkermansia , Ligilactobacillus , and Ruminococcaceae , which were negatively correlated with arthritis severity. CA treatment was associated with increased fecal SCFA levels in CIA rats. Collectively, these findings indicate that CA administration is associated with normalization of the gut microbiota, enhancement of intestinal barrier function, and amelioration of arthritis symptoms in CIA rats, suggesting that the interplay among gut dysbiosis, intestinal barrier damage, and arthritis may represent a contributing factor in the pathogenesis of RA.