Artemisia argyi-enriched fermented soybean meal alleviates ETEC K88-induced intestinal injury in mice in association with gut microbiota remodeling and purine metabolic alterations

BACKGROUND: Enterotoxigenic Escherichia coli (ETEC) K88 is an important enteric pathogen associated with diarrhea, intestinal barrier dysfunction, and gut microbial dysbiosis. Fermented soybean meal (FSBM) has shown potential for improving intestinal health, but its effects on ETEC-induced injury and the related microbiota-metabolite changes remain unclear. METHODS: Male BALB/c mice were assigned to control, model, chlortetracycline, and FSBM groups. After ETEC K88 challenge, growth performance, diarrhea score, serum cytokines and immunoglobulins, colonic tight-junction gene expression, fecal physicochemical characteristics, cecal microbiota composition by 16 S rRNA sequencing, and cecal metabolomic profiles by untargeted LC-MS were analyzed. RESULTS: FSBM improved body-weight recovery and alleviated diarrhea in ETEC K88-challenged mice. It reduced serum TNF-α and IFN-γ levels, increased IL-10, IgA, and IgG levels, and upregulated colonic ZO-1 and ZO-2 expression. FSBM also decreased fecal pH, increased lactic acid and acetic acid levels, and promoted lactic acid bacteria proliferation. In addition, FSBM reshaped the cecal microbial community, notably enriching Lactobacillus and other beneficial taxa. Metabolomic analysis revealed a distinct metabolic profile in the FSBM group, with purine metabolism identified as the most prominent altered pathway. CONCLUSIONS: FSBM alleviated ETEC K88-induced intestinal injury in mice and was associated with alterations in gut microbiota composition and purine metabolism. These findings support the potential of FSBM as a functional nutritional strategy for improving intestinal health under enteric stress.