Lactobacillus acidophilus LA15 plus Bifidobacterium animalis subsp. lactis Bi66 mitigates cyclophosphamide‐induced immunosuppression in association with gut–immune axis modulation and AhR signaling recovery

BACKGROUND: Cyclophosphamide (CTX), a widely used alkylating chemotherapeutic agent, causes severe systemic immunosuppression and gut microbiota dysbiosis through non-specific cytotoxicity, increasing infection risk and impairing chemotherapy outcomes. Safe and effective adjuvant therapies for chemotherapy-related immune injury remain limited. This study evaluated the protective effect of compound AB probiotics (Lactobacillus acidophilus LA15 combined with Bifidobacterium animalis subsp. lactis Bi66) against CTX-induced immunosuppression in mice and explored correlations associated with the gut-immune axis. RESULTS: CTX challenge induced immune organ atrophy, cytokine imbalance, impaired innate and adaptive immunity, intestinal barrier disruption, reduced short-chain fatty acid (SCFA) synthesis and gut dysbiosis. AB probiotic intervention alleviated these injuries dose-dependently: it restored thymus and spleen indexes, rebalanced serum cytokines, improved core immune functions, and repaired ileal mucosal pathological damage. Furthermore, probiotic treatment was accompanied by elevated fecal SCFA concentrations, upregulated tight junction gene expression, recovered aryl hydrocarbon receptor (AhR)/ERK/STAT3 transcription, enriched beneficial bacterial genera, and suppressed opportunistic pathogens. CONCLUSION: Compound AB probiotics alleviate CTX-induced immunosuppression in mice, and this effect correlates with restored gut microecology, enhanced SCFA metabolism, repaired intestinal barrier, and activated AhR signaling. These findings provide evidence for developing probiotic preparations as adjuvant interventions against chemotherapy-related immunosuppression.