Lactobacillus murinus Mediates Multi-Target Protection to Alleviate Cyclophosphamide-Induced Intestinal Injury and Immune Suppression Through the Gut–Metabolism–Immune Axis

The protective effects of Lactobacillus murinus on chemotherapy-related intestinal injury and immune imbalances were explored by establishing a cyclophosphamide (CTX)-induced mouse model of immunosuppression. CTX treatment led to intestinal barrier destruction, exacerbated local inflammation, and significantly reduced short-chain fatty acid levels (especially butyrate), accompanied by systemic immune suppression. Lactobacillus murinus intervention, especially at medium and high doses, dose-dependently repaired the intestinal barrier, inhibited inflammatory responses, restored levels of metabolites such as butyrate, and systematically regulated splenic immune cell proportions, restoring the CD4+/CD8+ balance. Metabolomic analysis further revealed that, at different doses, this regulation affected distinct metabolic pathways: low doses enhanced glutathione and purine metabolism, medium doses restored folate and steroid hormone metabolism, and high doses promoted fatty acid β-oxidation and galactose metabolism, forming a multi-level metabolic protective network. This suggests that L. murinus can alleviate chemotherapy-induced intestinal mucositis and mitigate systemic immune suppression through a dual local anti-inflammatory and systemic immune-regulatory effect, with potential mechanisms related to butyrate-mediated regulation of the “metabolism–immune axis,” providing evidence for probiotic-assisted chemotherapy.