Dietary Pichia Guilliermondii Improves Intestinal Digestive Capacity and Barrier Integrity in Weaned Piglets Associated with Gut Microbiota-Related Glutathione Metabolism.

Yeast-derived feed additives are increasingly used to support intestinal health after weaning, but dose-response evidence and mechanistic information for inactivated Pichia guilliermondii product (PG) in pigs remain limited. A total of 360 piglets (initial body weight, 6.30 ± 0.06 kg) received diets containing 0, 800, 1600, 2400, or 3200 mg/kg inactivated PG product for 28 days. Under the present experimental conditions, the 800 mg/kg PG group showed the greatest weight gain, final body weight, and nutrient digestibility of dry matter and crude protein among the tested dietary levels (P < 0.05). Accordingly, the control and 800 mg/kg PG (PGO) groups were selected for downstream phenotyping. Compared with controls, PGO group had increased intestinal villus height, digestive enzyme activities, nutrient transporter expression, goblet cell numbers, and tight-junction protein abundance, and reduced serum diamine oxidase activity (P < 0.05). The PGO group also showed higher systemic and intestinal antioxidant-related indices, accompanied by increased expression of SOD1, GPX4, and NRF2 (P < 0.05). Microbiota analysis showed enrichment of potentially beneficial taxa, including Blautia, Prevotellaceae_NK3B31_group, and Prevotella_9. Colonic metabolomics further revealed higher levels of glycine, serine, and L-cysteine, together with increased intestinal activities and gene/protein expression of glutathione-related enzymes/factors, including GCLM, GCLC, and GSS (P < 0.05). These findings indicate that, under the present experimental conditions, 800 mg/kg inactivated PG product was the best-performing tested dose for supporting growth, nutrient utilization, antioxidant-related indices, and intestinal barrier-related indices in weaned piglets, and these responses were associated with changes in gut microbiota-related glutathione metabolism.