Electroacupuncture Modulates Microbial Phenylalanine Metabolism and Enhances the Intestinal Barrier Function to Alleviate Colitis in Mice

Lei Zhu,1,* Ryan Au,2,* Luming Dai,3,* Yanan Li,2 Feng Xu,2 Yuan Cui,2 Jingyi Hu,1 Hong Shen1 1Digestive Disease Research Institute, Affiliated Hospital of Nanjing University of Chinese Medicine, City Nanjing, People’s Republic of China; 2First Clinical Medical College, Nanjing University of Chinese Medicine, City Nanjing, People’s Republic of China; 3Digestive Department, Affiliated Hospital of Nanjing University of Chinese Medicine, City Nanjing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hong Shen; Jingyi Hu, Digestive Disease Research Institute, Affiliated Hospital of Nanjing University of Chinese Medicine, City Nanjing, People’s Republic of China, Email [email protected]; [email protected]: Electroacupuncture (EA) exerts beneficial effects on ulcerative colitis. However, its underlying mechanisms remain elusive. In this study, we investigated the impact of high and low-frequency EA at Zusanli (ST36) on the gut microbiota and metabolite profile in the dextran sulfate sodium (DSS)-induced colitis mouse model.Methods: Colitis was established using DSS, and daily electroacupuncture at ST36 with varying frequencies was administered. Changes in body weight and fecal characteristics were monitored. Pro-inflammatory cytokines were detected, and the core molecule of intestinal barrier function were analyzed. The composition of intestinal flora was analyzed using 16S sRNA sequencing, while the changes of metabolites in colon tissue were detected by Ultra-performance liquid chromatography–tandem mass spectrometry (UPLC/MS/MS).Results: Treatment with both high and low frequencies of EA at ST36 significantly ameliorated the symptoms of colitis, while also exerting systemic and local anti-inflammatory effect by downregulating the proinflammatory cytokines, iNOS and MPO. EA at ST36 enhanced the intestinal barrier by upregulating the expression of MUC2 and ZO-1. Furthermore, high-frequency EA at ST36 remarkably restored the gut microbial composition and diversity, as well as modulated the gut microbial metabolism of phenylalanine.Conclusion: Our results suggest that EA treatment may alleviate colitis by reducing colon damage through gut microbiota-phenylalanine metabolism, which provides insight into EA’s underlying mechanisms in the treatment of colitis.Keywords: ulcerative colitis, electroacupuncture, gut microbiota, phenylalanine metabolism