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Caffeic acid (CA) is one of the major phenolic acids of coffee with multiple biological activities. Our previous study found that 500 mg/kg of chlorogenic acid (CGA) had the potential capacity of alleviating colonic inflammation. Moreover, CGA can be degraded into caffeic acid (CA) by the gut microbiota in the colon. Therefore, we hypothesize that CA can exert protective effects on colonic inflammation. To test the hypothesis, 251 mg/kg CA was supplemented to DSS-induced colitis mice. The results showed that CA treatment recovered DSS-induced disease activity index (DAI), colon length, and histopathology scores of colon tissue. Additionally, CA treatment significantly decreased pro-inflammatory cytokines and malondialdehyde (MDA) levels and increased the level of IL-10, total antioxidant capacity (T-AOC), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) in serum. qPCR results indicated that CA treatment dramatically downregulated mRNA expression of  IL-1β ,  IL-6 , and  TNF-α  as well as upregulated  SOD1 ,  GPX1 ,  GPX2 ,  CAT , and  IL-10 . In addition, CA supplementation significantly increased mRNA expression of  Nrf-2 ,  HO-1 , and  NQO1 , which showed its antioxidant and anti-inflammatory capacities potentially by activating the Nrf-2/HO-1 pathway. Moreover, CA supplementation prevented gut barrier damage by enhancing  Occludin  gene expression. Furthermore, CA supplementation altered the gut microbiome composition by decreasing the relative abundance of  Bacteroides  and  Turicibacter , and enhancing the relative abundance of  Alistipes  and  Dubosiella . Meanwhile, CA supplementation increases the abundance of  Dubosiella  and  Akkermansia . In conclusion, CA supplementation could effectively alleviate DSS-induced colitis by improving the defense against oxidative stress and inflammatory response.

Caffeic Acid Supplement Alleviates Colonic Inflammation and Oxidative Stress Potentially Through Improved Gut Microbiota Community in Mice