Early-Life Diarrhea Disrupts Antioxidant–Immune Homeostasis and Gut Microbiota in Suckling Calves

Calf diarrhea is a common early-life disorder that adversely affects growth, oxidative balance, immune function, and intestinal microbiota, thereby compromising health and production performance. This study systematically investigates the effects of naturally occurring diarrhea in 7-day-old suckling calves on oxidative stress, immune responses, intestinal barrier integrity, and gut microbiota structure and function. Fecal scores, serum antioxidant and immune indices, and intestinal permeability markers were measured, and fecal samples were subjected to metagenomic sequencing. Diarrhea-affected calves exhibited higher fecal scores, increased oxidative stress indicated by reduced total antioxidant capacity, elevated lipid peroxidation, and altered antioxidant enzyme activities. Humoral immunity was impaired, inflammatory responses were dysregulated, and intestinal barrier function was disrupted. Gut microbial diversity declined, showing a depletion in health-associated taxa and the enrichment of opportunistic pathogens. Correlation analyses revealed that pathogenic bacteria abundance positively associated with diarrhea severity, oxidative stress, inflammation, and barrier disruption, while beneficial genera correlated with antioxidant and immune function. Functional profiling indicated a microbial shift from amino acid metabolism and antioxidant homeostasis toward carbohydrate and energy metabolism under diarrheic conditions. These findings highlight the pivotal role of gut microbiota dysbiosis in diarrhea pathogenesis and provide a foundation for developing microbiome-targeted interventions to improve calf health.