Coumarin derivatives ameliorate the intestinal inflammation and pathogenic gut microbiome changes in the model of infectious colitis through antibacterial activity

• Published in: Frontiers in cellular and infection microbiology 2024-07, Vol.14, p.1362773
• Main Authors: Jung, Hui-Su, Park, Yei Ju, Gu, Bon-Hee, Han, Goeun, Ji, Woonhak, Hwang, Su Mi, Kim, Myunghoo
• Format: Article
• Language: English
• Subjects: Animals; Anti-Bacterial Agents - pharmacology; anti-inflammation; antibacterial activity; Bacteria - classification; Bacteria - drug effects; Cellular and Infection Microbiology; Colitis - drug therapy; Colitis - microbiology; coumarin derivative; Coumarins - pharmacology; Cytokines - metabolism; Disease Models, Animal; Gastrointestinal Microbiome - drug effects; gut immunity; gut microbiome; Inflammation - drug therapy; Male; Mice; Mice, Inbred C57BL; Th1 Cells - drug effects; Th1 Cells - immunology; Th17 Cells - drug effects; Th17 Cells - immunology
• ISSN: 2235-2988; 2235-2988
• DOI: 10.3389/fcimb.2024.1362773

Coumarin, a phenolic compound, is a secondary metabolite produced by plants such as Tanga and Lime. Coumarin derivatives were prepared via Pechmann condensation. In this study, we performed and experiments to determine the antimicrobial and gut immune-regulatory functions of coumarin derivatives. For the antimicrobial activity assay, coumarin derivatives C1 and C2 were selected based on their pathogen-killing activity against various pathogenic microbes. We further demonstrated that the selected coumarin derivatives disrupted bacterial cell membranes. Next, we examined the regulatory function of the coumarin derivatives in gut inflammation using an infectious colitis model. In an infectious colitis model, administration of selected C1 coumarin derivatives reduced pathogen loads, the number of inflammatory immune cells (Th1 cells and Th17 cells), and inflammatory cytokine levels (IL-6 and IL-1b) in the intestinal tissue after pathogen infection. In addition, we found that the administration of C1 coumarin derivatives minimized abnormal gut microbiome shift-driven pathogen infection. Potential pathogenic gut microbes, such as and , were increased by pathogen infection. However, this pathogenic microbial expansion was minimized and beneficial bacteria, such as and , increased with C1 coumarin derivative treatment. Functional gene enrichment assessment revealed that the relative abundance of genes associated with lipid and nucleotide metabolism was reduced by pathogen infection; however, this phenomenon was not observed in C1 coumarin derivative-treated animals. Collectively, our data suggest that C1 coumarin derivative is effective antibacterial agents that minimize pathogen-induced gut inflammation and abnormal gut microbiome modulation through their antibacterial activity.