# Immune-Modulatory Mechanism of Compound Yeast Culture in the Liver of Weaned Lambs

## TL;DR

This study shows that adding a compound yeast culture to lambs' diets improves liver health and immune balance during the weaning period.

## Contribution

The study reveals the immune-modulatory mechanism of a compound yeast culture in lamb livers using transcriptomics and bioinformatics.

## Key findings

- CYC improved liver structure and antioxidant defenses in weaned lambs.
- CYC modulated immune responses by altering cytokine levels and activating PI3K–AKT signaling.
- Transcriptomic analysis identified key genes and pathways involved in CYC's immune-regulatory effects.

## Abstract

Weaning is a stressful transition period for lambs, often associated with oxidative stress, immune dysregulation, and compromised liver function. This study investigated whether supplementation of the daily ration with a compound yeast culture (CYC), a co-culture of Saccharomyces cerevisiae and Kluyveromyces marxianus, could support hepatic function in weaned lambs. CYC supplementation improved liver tissue structure, enhanced antioxidant defenses by increasing T-SOD, GSH-Px, and T-AOC activities while reducing lipid peroxidation product MDA, and balanced immune responses by modulating pro- and anti-inflammatory cytokine levels. Molecular analyses revealed that CYC upregulated PI3K–AKT signaling, contributing to maintenance of liver structure and immune homeostasis. Collectively, these findings indicate that inclusion of CYC in the daily ration is an effective nutritional strategy to support liver integrity, reinforce immune and oxidative balance, and help lambs better cope with weaning-associated challenges.

Compound yeast culture (CYC) is known to enhance animal health, but its effects on hepatic immune function are unclear. This study systematically examined CYC’s regulatory effects on the liver of weaned lambs using transcriptomics and integrative bioinformatics. Ten lambs were randomly assigned to a control diet or a basal diet supplemented with 30 g/d per head of Saccharomyces cerevisiae and Kluyveromyces marxianus co-culture (CYC group) for 42 days. Histological analysis showed that CYC improved hepatocyte arrangement and sinusoidal integrity, suggesting enhanced hepatic tissue stability. Cytokine analysis revealed CYC significantly increased IL-6 and IL-1β while reducing IL-10, TGF-β1, TNF-α, and CXCL9, indicating a bidirectional modulation of the immune response. Additionally, CYC enhanced antioxidant defenses by increasing T-SOD, GSH-Px, and T-AOC activities and decreasing MDA content. Transcriptomic sequencing indicated that CYC reshaped hepatic gene expression. Upregulated genes were enriched in immune-regulatory and structural pathways, including PI3K-AKT signaling, ECM–receptor interactions, Toll-like receptor pathways, and cell adhesion molecules. Protein-level validation further confirmed activation of PI3K and AKTAKT phosphorylation with limited engagement of NF-κB signaling. Conversely, downregulated genes were mainly associated with oxidative stress and energy metabolism, such as ROS-related pathways and MAPK signaling. WGCNA identified key hub genes (PTPRC, CD86, and ITGAV), which correlate with pro-inflammatory factors and participate in immune recognition, T-cell activation, and cell adhesion. These data suggest that CYC promotes hepatic immune homeostasis by enhancing immune signaling, stabilizing tissue architecture, and modulating oxidative stress/metabolic processes. This study provides mechanistic insights into CYC’s regulation of liver immune function and supports its targeted application as a functional feed additive for ruminants.