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<p>Ulcerative colitis (UC) is a chronic inflammatory bowel disease with limited non-invasive biomarkers and variable responses to probiotics. This study investigates the probiotic potential of <i>Enterococcus hirae</i> Y-HS isolated from healthy beef cattle and its mechanisms in alleviating UC. In vitro probiotic properties of Y-HS were assessed. Public transcriptomic datasets (GSE179285, GSE87466, GSE206285) were analysed to identify differentially expressed genes in UC patients. Machine learning integrated with protein-protein interaction network analysis identified core diagnostic genes. A DSS-induced murine colitis model was established to evaluate Y-HS intervention effects. Y-HS exhibited excellent gastrointestinal tolerance, no haemolytic activity and antibiotic susceptibility. Transcriptomic analysis identified 768 DEGs in UC patients. Machine learning yielded four metabolism-associated signature genes—CYP3A4, UGT1A6, HSD17B6 and SRD5A3—with diagnostic accuracy (AUC 0.72–0.84). In DSS-induced colitis, Y-HS dose-dependently attenuated disease activity, remodelled gut microbiota (increasing <i>Lactobacillus</i>, decreasing <i>Escherichia-Shigella</i>), activated PXR/Nrf2 signalling, upregulated detoxification enzymes (CYP3A4, UGT1A6) and tight junction proteins, while downregulating HSD17B6, SRD5A3 and cleaved caspase-3. These changes were accompanied by reduced pro-inflammatory cytokines and elevated IL-10. <i>E. hirae</i> Y-HS alleviates UC through coordinated modulation of gut microbiota, host metabolism, inflammation and barrier function. The identified metabolic gene signature offers potential non-invasive biomarkers for UC.</p>

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Enterococcus hirae Y-HS Alleviates Ulcerative Colitis by Activating PXR/Nrf2-mediated Metabolic-immune Crosstalk

  • 期刊论文

  • 发表日期：

    2026年7月7日

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  • Fuming You,
  • Han Bao,
  • Wentong Li,
  • Hanzhao Zhang,
  • Yang Li,
  • Jiang Li,
  • Mingao Sun,
  • Yuxia Yang,
  • Luomeng Chao

摘要

Ulcerative colitis (UC) is a chronic inflammatory bowel disease with limited non-invasive biomarkers and variable responses to probiotics. This study investigates the probiotic potential of Enterococcus hirae Y-HS isolated from healthy beef cattle and its mechanisms in alleviating UC. In vitro probiotic properties of Y-HS were assessed. Public transcriptomic datasets (GSE179285, GSE87466, GSE206285) were analysed to identify differentially expressed genes in UC patients. Machine learning integrated with protein-protein interaction network analysis identified core diagnostic genes. A DSS-induced murine colitis model was established to evaluate Y-HS intervention effects. Y-HS exhibited excellent gastrointestinal tolerance, no haemolytic activity and antibiotic susceptibility. Transcriptomic analysis identified 768 DEGs in UC patients. Machine learning yielded four metabolism-associated signature genes—CYP3A4, UGT1A6, HSD17B6 and SRD5A3—with diagnostic accuracy (AUC 0.72–0.84). In DSS-induced colitis, Y-HS dose-dependently attenuated disease activity, remodelled gut microbiota (increasing Lactobacillus, decreasing Escherichia-Shigella), activated PXR/Nrf2 signalling, upregulated detoxification enzymes (CYP3A4, UGT1A6) and tight junction proteins, while downregulating HSD17B6, SRD5A3 and cleaved caspase-3. These changes were accompanied by reduced pro-inflammatory cytokines and elevated IL-10. E. hirae Y-HS alleviates UC through coordinated modulation of gut microbiota, host metabolism, inflammation and barrier function. The identified metabolic gene signature offers potential non-invasive biomarkers for UC.