Dietary supplementation of hydrolyzed yeast from Kluyveromyces fragilis with or without high-dose zinc oxide modulates growth performance and diarrhea incidence of weaned pigs by improving intestinal health

Hydrolyzed yeast from Kluyveromyces fragilis (HK) is nutrient-rich, and we hypothesized dietary HK could improve weaned pigs growth performance and health, serving as a potential alternative to high-dose zinc oxide (ZnO). A total of 160 weaned pigs (body weight, BW: 8.87 ± 0.58 kg; 28 ± 1 days) were randomly allotted into 4 treatments (n = 8 per treatment) in a 2 × 2 factorial treatment arrangement, comparing ZnO inclusion (ZnO- or ZnO+, 2 g/kg in the prestarter and 0 g/kg in the starter) with or without HK (10 g/kg in the prestarter and 5 g/kg in the starter) for 42 days. High-dose ZnO improved growth and reduced diarrhea incidence from day 0–14, whereas HK enhanced growth during days 0–42 and also alleviated diarrhea in the first 14 days (P < 0.05). Additionally, high-dose ZnO increased plasma catalase (CAT) activity and immunoglobulin A concentration while reducing malondialdehyde (P < 0.05). Similarly, HK enhanced plasma CAT, superoxide dismutase, immunoglobulin A, and immunoglobulin G (P < 0.05) and lowered malondialdehyde (P = 0.017). At the intestinal level, ZnO downregulated jejunal interleukin-8, interleukin-1β, and interleukin-10 mRNA expression (P < 0.05), while HK increased secretory immunoglobulin A concentration, upregulated Nrf2 and CAT expression, and reduced interleukin-6 expression (P < 0.05). Morphologically, HK improved villus height-to-crypt depth ratios across intestinal segments and increased villus height in the duodenum (P < 0.05). Microbiota analysis showed that ZnO enriched Bacteroidota, Actinobacteriota, and Prevotella but reduced Campilobacterota and Escherichia-Shigella, while HK decreased UCG-009 and modulated Prevotellaceae- and Lachnospiraceae-related taxa (P < 0.05). In conclusion, dietary HK improved growth performance, reduced diarrhea incidence, and enhanced antioxidant capacity, immune capacity, intestinal, and microbial status in weaned pigs, supporting its potential as an alternative to ZnO.