Ludangshen oral liquid ameliorates cyclophosphamide-induced immunosuppression in mice: Insights from metabolomic, gut microbiota, and multi-omics correlation analyses.

Abelmoschus manihot (L.) leaf flavonoids (AMLF) restore cyclophosphamide-induced immunosuppression in mice via gut microbiota and serum metabolomics modulation.

Immune homeostasis serves as the foundation for disease prevention and the cornerstone for ensuring human health. The effects of Abelmoschus manihot (L.) leaf flavonoids (AMLF) on restoring immune function were investigated in a cyclophosphamide (CTX)-induced immunosuppressed mouse model. The underlying repair mechanisms were explored by an integrative analysis of intestinal microbiomics and serum metabolomics. The results demonstrated that AMLF markedly elevated the spleen and thymus indices, promoted the proliferation of splenic lymphocytes in the presence of concanavalin A (ConA) or lipopolysaccharide (LPS) and CD4+ and CD8+ T lymphocyte subsets, and concomitantly enhanced the serum levels of key immunomodulatory cytokines, including interleukin-1β (IL-1β), interleukin-2 (IL-2), and tumor necrosis factor-α (TNF-α), and the antibody immunoglobulin G (IgG). In addition, AMLF treatment effectively mitigated CTX-induced histopathological injuries to immune organs and the colon. AMLF were also found to protect the liver by regulating antioxidant enzyme activities. Furthermore, AMLF markedly improved the intestinal microbial community structure, promoted the enrichment of beneficial bacteria (Lactobacillaceae and Prevotellaceae), inhibited pathogenic bacteria (Muribaculaceae and Desulfovibrionaceae), and increased the content of short-chain fatty acids (SCFAs). Serum metabolomic analysis showed that AMLF upregulated the levels of leukotrienes, S-(PGA1)-glutathione and prostaglandin E2. Correlation analysis identified g_Alistipes, g_norank_f_Muribaculaceae, and g_Kurthia as potential microbiota strongly associated with the restoration of immune and metabolic homeostasis after AMLF treatment. These findings support the dual potential of AMLF in functional foods and as immunomodulatory adjuvants.

Treatment with Biaoxu Ganmao Granules ameliorates cyclophosphamide-induced immunosuppression in mice: Paeoniflorin-associated modulation of the TLR4/NF-κB pathway.

BXGG partially reversed CTX-associated reductions in body weight, thymus and spleen indices and partially restored serum interleukin-2, interleukin-4 (IL-4), and interferon-gamma (IFN-γ) levels, and white blood cell, lymphocyte, platelet, and reticulocyte counts.

Immunoregulatory Activity of Chinese Yam Polysaccharides on Cyclophosphamide-Induced Immunosuppression Mice via Regulating Gut Microbiota and Metabolic Pathway

Pasteurized Akkermansia muciniphila AKK PROBIO ameliorates inflammation and metabolic disorder in db/db mice with alterations in gut microbiota and hepatic TLR4/NF-κB and SREBP2/HMGCR signaling.

BACKGROUND Diabetes mellitus, especially type 2 diabetes mellitus (T2DM), represents a significant global health challenge. Growing evidence indicates that Akkermansia muciniphila, a promising next-generation beneficial microorganism, could help alleviate metabolic disorders. Nevertheless, its strain-specific effects and associated mechanisms require further investigation. Here, we investigated the potential effects of pasteurized A. muciniphila AKK PROBIO in T2DM using db/db mice. RESULTS Our findings show that pasteurized AKK PROBIO supplementation was associated with lower fasting glucose levels, reduced inflammatory markers, and improved cholesterol balance in db/db mice. Pasteurized AKK PROBIO administration was accompanied by changes in gut microbiota composition, including enrichment of bacterial taxa linked to short-chain fatty acid (SCFA) production, and by increased GLP-1 levels and altered serum metabolites, including 9,9'-di-cis-ζ-carotene and l-arginine. These changes were paralleled by reduced hepatic expression of proteins related to the TLR4/MyD88/IKKα/NF-κB and SREBP2/HMGCR signaling pathways. CONCLUSIONS Taken together, our findings indicate that pasteurized AKK PROBIO ameliorates metabolic disorder and inflammation in db/db mice, accompanied by changes in gut microbial ecology, serum metabolites, and hepatic inflammatory/lipid metabolic signaling. This study supports pasteurized A. muciniphila AKK PROBIO as a postbiotic for further investigation in metabolic disorders. © 2026 Society of Chemical Industry.

The immunomodulatory effects of Bifidobacterium lactis XLTG11 on cyclophosphamide-induced immune dysfunction in mice.

Previous studies have demonstrated that Bifidobacterium lactis (B. lactis) XLTG11 exerts significant immunomodulatory effects. However, the underlying mechanisms remain unclear. To investigate these mechanisms, BALB/c mice were randomly divided into three groups: normal control (NC), model control (MC), and B. lactis XLTG11 (XL) groups. We assessed spleen and thymus indices, jejunal histopathology, leukocyte and IgA cell counts, as well as the levels of interferon (IFN)-γ, interleukin (IL)-2, IL-4, IL-12, and secretory IgA (SIgA) in the small intestine. We also analysed the composition and diversity of the gut microbiota. The results showed that B. lactis XLTG11 restored villus height and crypt depth, thereby alleviating jejunal tissue damage. Furthermore, B. lactis XLTG11 treatment significantly increased the counts of leukocytes, goblet cells, and IgA cells, and elevated the levels of the aforementioned cytokines and SIgA. It also increased thymus indices without affecting spleen indices. Regarding the gut microbiota, B. lactis XLTG11 reduced the Bacillota/Bacteroidota ratio and modulated microbial composition and diversity. Spearman's correlation analysis revealed significant associations between specific microbial taxa and the immune parameters measured above. Collectively, these findings demonstrate that B. lactis XLTG11 can modulate immune function, and the underlying mechanisms involve repairing the intestinal mucosal barrier, regulating the levels of immune cells and cytokines, and maintaining gut microbiota homeostasis.

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. © 2026 Society of Chemical Industry.