Search

Abstract In recent years, the development of immunosuppression has become common, and probiotics are a vital immunomodulatory strategy. This study evaluated the alleviating effect of Lactiplantibacillus plantarum (L. plantarum) YY‐112 on cyclophosphamide‐induced immune imbalance and resolved the possible mechanism of action. L. plantarum YY‐112 at 109 CFU/mL lowered loss of body weight and alleviated splenic injury, intestinal injury, and inflammation, according to the hematoxylin and eosin staining. Biochemical results showed that 109 CFU/mL L. plantarum YY‐112 increased interleukin‐10 and immunoglobulin M levels and decreased interferon‐γ levels. Additionally, the immunoregulatory effect at the molecular levels of L. plantarum YY‐112 was analyzed by transcriptome sequencing. L. plantarum YY‐112 significantly upregulated Cr2 and downregulated C5aR1 to regulate the complement system; downregulated S100a8, S100a9, and Mmp9 to inhibit neutrophil aggregation; upregulated Cd19, Cd72, Cd3e, Cd28, Cd80, Cd8a, and histocompatibility‐2‐related genes to regulate B‐ and T‐cell activation; and upregulated Xiap, Malt1, Ikbkb, Mapk11, Mef2c, Mapk12, Ras, and Myc to activate immune signaling pathways. Furthermore, L. plantarum YY‐112 improved intestinal microbial structure and reduced enrichment of Lachnospiraceae_NK4A136_group, norank_f_Lachnospiraceae, Desulfovibrio, Colidextribacter, and Helicobacter. In conclusion, these findings offer valuable insights into the potential mechanisms through which L. plantarum YY‐112 regulates immune imbalance.