Kluyveromyces lactis Hydrolysate Enhances Growth Performance and Reduces Diarrhea Rate by Modulating Immune Function and Regulating Gut Microbiota in Weaned Piglets

This study assessed the effect of dietary supplementation with Kluyveromyces lactis (K. lactis) hydrolysate (HKL) on growth performance, apparent nutrient digestibility, systemic immune–antioxidant status, and fecal microbiota in weaned piglets. A total of fifty-four piglets, with an initial body weight of 6.07 ± 0.086 kg and age of 25 ± 1 days, were randomly assigned to three dietary treatments over 28 days (6 replicates per treatment; 3 piglets per replicate): a control diet (CON), CON supplemented with 5 g/kg HKL (HKL1), or CON supplemented with 10 g/kg HKL (HKL2). Throughout the trial, growth performance was monitored, apparent total tract digestibility of nutrients was determined, serum samples were collected for immune and antioxidant assessments, and fecal samples were gathered for microbiota analysis. The results indicated that compared to the CON group, both HKL1 and HKL2 groups exhibited improved growth performance, as evidenced by increased average daily feed intake (ADFI) from day 0 to 28 (p < 0.05). Furthermore, HKL2 significantly enhanced average daily gain (ADG) from day 0 to 14 and reduced the feed-to-gain ratio (F: G) during the same period (p < 0.05). Diarrhea incidence was markedly decreased by HKL supplementation at both day 1–14 and day 15–28 (p < 0.001). HKL supplementation increased the apparent digestibility of dry matter, ash, calcium, and phosphorus (p < 0.05). On day 14, serum total protein and immunoglobulin A (IgA) levels were elevated, while malondialdehyde (MDA) levels were reduced in HKL-supplemented piglets (p < 0.05). By day 28, serum immunoglobulin G (IgG) concentrations, as well as superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities, were increased, while interleukin-6 (IL-6) levels were decreased in HKL-supplemented piglets (p < 0.05), suggesting HKL possesses immunomodulatory and antioxidant regulatory capacities. HKL also enriched several health-associated commensal bacteria, including [Eubacterium]_xylanophilum_group, unclassified_f_Peptostreptococcaceae, Candidatus Saccharimonas, Erysipelotrichaceae_UCG-003, and Negativibacillus, suggesting a microbiota-modulatory effect in weaned piglets. These results indicate that dietary supplementation with HKL could improve growth performance and nutrient utilization, reduce post-weaning diarrhea, and promote a more favorable immune–antioxidant status and microbial profile in weaned piglets, with the 10 g/kg dosage demonstrating greater overall efficacy. These findings provide a theoretical basis for the development of novel K. lactis products and the application of K. lactis hydrolysate in weaned piglets.