Integrated Metabolomics and Gut Microbiome Analysis Reveals the Efficacy of a Phytochemical Constituent in the Management of Ulcerative Colitis

SCOPE: Cinnamaldehyde (CAH), a phytochemical constituent isolated from cinnamon, is gaining attention due to its nutritional and medicinal benefits. This study aimed to investigate the potential role of CAH in the treatment of ulcerative colitis (UC). METHODS AND RESULTS: Integrated metabolomics and gut microbiome analysis are performed for 2,4,6-trinitrobenzenesulfonic acid (TNBS) induced UC rats. The effect of CAH on colonic inflammation, lipid peroxidation, metabolic profiles, and gut microbiota is systematically explored. It finds that CAH improves the colitis-related symptoms, decreases disease activity index, increases the colon length and body weight, and alleviates histologic inflammation of UC rats. These therapeutic effects of CAH are due to suppression of inflammation and lipid peroxidation. Moreover, multi-omics analysis reveals that CAH treatment cause changes in plasma metabolome and gut microbiome in UC rats. CAH regulates lipid metabolic processes, especially phosphatidylcholines, lysophosphatidylcholines, and polyunsaturated fatty acids. Meanwhile, CAH modulates the gut microbial structure by restraining pathogenic bacteria (such as Helicobacter) and increasing probiotic bacteria (such as Bifidobacterium and Lactobacillus). CONCLUSIONS: These results indicate that CAH exerts a beneficial role in UC by synergistic modulating the balance in gut microbiota and the associated metabolites, and highlights the nutritional and medicinal value of CAH in UC management.