Abstract

Objective Xuanfei Baidu decoction (XFBD), one of China’s recommended prescriptions for COVID-19, has demonstrated clinical efficacy in mitigating gastrointestinal inflammation associated with SARS-CoV-2 infection, yet its exact therapeutic mechanism remains incompletely understood, necessitating further in vivo investigation. In this study, we utilized a fruit fly (Drosophila melanogaster) model of intestinal inflammation to assess the therapeutic potential and underlying mechanisms of XFBD in ameliorating intestinal inflammation. Methods We induced intestinal inflammation in D. melanogaster by dextran sulfate sodium (DSS) administration. We examined XFBD’s protective effects on D. melanogaster’s intestine and explored changes in the IMD and JNK-JAK/STAT signaling pathways. Furthermore, we analyzed the intestinal microbiota through 16S rRNA gene sequencing. Results XFBD effectively mitigated DSS-induced intestinal inflammation, leading to a significant extension of the flies’ lifespan. It enhanced the integrity of intestinal barrier while reducing reactive oxygen species (ROS) levels in intestine. Additionally, XFBD restored the disrupted intestinal microbiota by regulating immune homeostasis, notably inhibiting the IMD, Toll, and JNKJAK/STAT pathways. Furthermore, the reintroduction of symbiotic microbiota partially alleviated the DSS-induced dysregulation. Conclusion In conclusion, our study underscores the therapeutic potential of XFBD for intestinal inflammation, providing valuable insights into its key mechanisms and highlighting the pivotal role of symbiotic microbiota in anti-inflammatory responses and immune pathway regulation.