Polyphenol-rich diet mediates interplay between macrophage-neutrophil and gut microbiota to alleviate intestinal inflammation

Dietary phenolic acids alleviate intestinal inflammation by modifying gut microbiota composition and regulating macrophage activation. This study investigated how individual phenolic acids affect the interaction between intestinal microbiota and macrophages in inflammatory bowel disease (IBD). Mice with or without macrophage depletion were administered four phenolic acids (chlorogenic, ferulic, caffeic, and ellagic acids) after dextran sulfate sodium (DSS) treatment. Gut microbiota depletion and fecal microbiota transplantation were also performed. Results showed that microbiota and macrophage absence worsened DSS colitis. Chlorogenic acid reduced colitis by suppressing M1 macrophage polarization via Pkm2-dependent glycolysis and NLRP3 activation inhibition. Ferulic acid's effects were neutrophil-dependent, reducing neutrophil extracellular traps. Caffeic and ellagic acid benefits depended on gut microbiota; ellagic acid's metabolite, urolithin A, alleviated colitis and enhanced gut barrier function in an IL22-dependent manner. The study demonstrates that phenolic acid protection against colitis arises from the interaction between gut microbiota and macrophage-neutrophil.

Dandan Han, Yujun Wu, Dongdong Lu, Jiaman Pang, Jie Hu, Xiangyu Zhang, Zhenyu Wang, Guolong Zhang, Junjun Wang