Integrative analysis of 16S rRNA sequencing and network pharmacology suggests protective effects of Sihuang Zhili Granules against APEC O78 challenge through gut homeostasis-related changes

IntroductionAvian pathogenic Escherichia coli (APEC) infection poses a serious threat to the poultry industry and is increasingly difficult to control because of antimicrobial resistance.MethodsThis study combined microbiota analysis and network pharmacology to investigate the protective effects of Sihuang Zhili Granules (SH) against APEC O78 challenge.ResultsPhenotypic analyses showed that SH treatment reduced mortality, partially improved growth-related performance, and alleviated histopathological lesions in the heart, liver, and spleen. At the mechanistic level, SH treatment was associated with increased mRNA expression of intestinal tight junction-related genes, including Occludin and Claudin-3, reduced serum levels of pro-inflammatory cytokines such as IL-1β, IL-6, and TNF-α, and improvement in selected serum biochemical disturbances induced by APEC O78 challenge. 16S rRNA gene sequencing showed that SH treatment was associated with changes in cecal microbiota composition, including a lower relative abundance of Escherichia–Shigella and enrichment of taxa such as members of the Ruminococcaceae family. Integrative network pharmacology and molecular docking analyses further suggested that compounds such as eupatorin and oroxylin A may participate in host responses to APEC infection through candidate inflammation- and barrier-related pathways.DiscussionThese findings support the potential of SH as a candidate intervention for APEC O78-associated disease in broilers, while the precise microbiota-related and molecular mechanisms require further experimental validation.