Compound Yeast Culture Reshapes Gut Microbiota and Functional Pathways to Enhance Antioxidant Capacity and Immune Homeostasis in Suckling Calves

Background: Diarrhea in suckling calves is associated with impaired growth, oxidative stress, immune dysfunction, and intestinal microbial dysbiosis. This study evaluated the effects of compound yeast culture (CYC) supplementation on growth performance, fecal characteristics, antioxidant capacity, immune function, and gut microbiota in diarrheic Holstein calves. Thirty-six approximately 7-day-old calves were enrolled, including 12 healthy calves (CON) and 24 diarrheic calves randomly assigned to a diarrhea group (DIA) or a CYC-supplemented group (DIA-YC; 50 g/d for 30 days). The experimental period lasted 60 days. Results: Compared with the DIA group, calves in the DIA-YC group showed significantly higher average daily feed intake and average daily gain (ADG) during days 31–60 and across the entire period (p < 0.05), with a trend towards increased body weight. Fecal scores were significantly elevated in diarrheic calves during the early and mid-stages but were markedly reduced by CYC supplementation from days 7 to 30; no significant difference was observed between DIA-YC and CON during days 16–30 (p > 0.05). Diarrheic calves exhibited oxidative stress, characterized by decreased total antioxidant capacity (T-AOC) and increased malondialdehyde (MDA). CYC supplementation significantly increased T-AOC, superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) activities, while reducing MDA levels (p < 0.05). Immune analysis showed higher serum IgG and IL-10 levels and lower TNF-α levels in the DIA-YC group, along with improved intestinal barrier indicators, including diamine oxidase (DAO) activity and endotoxin levels. Metagenomic analysis revealed that diarrhea reduced microbial richness and diversity and altered community structure, whereas CYC partially restored microbial diversity and increased beneficial genera such as Prevotella, Coprococcus, Ruminococcus, and Parabacteroides. Functional analysis indicated that CYC enhanced pathways related to immune regulation, energy metabolism, and antioxidant function. Conclusion: CYC supplementation alleviates oxidative stress and immune dysfunction by modulating gut microbiota, thereby improving growth performance and reducing diarrheal severity in calves.