Heat-inactivated Akkermansia muciniphila AKK-PROBIO ameliorates cyclophosphamide-induced immunosuppression via the NF-κB/MAPK pathway and gut microbiota modulation.

BACKGROUND

Immune dysfunction underlies numerous diseases. While Akkermansia muciniphila exhibits immunomodulatory potential, the efficacy of its heat-inactivated form remains incompletely characterized.

METHODS

This study investigated whether oral heat-inactivated A. muciniphila AKK PROBIO alleviates cyclophosphamide (CTX)-induced immunosuppression in mice and elucidated mechanisms. Mice received CTX injections followed by oral heat-inactivated A. muciniphila for 14 days. Analyses included body/organ indices, hematology (WBC, RBC, HGB, lymphocytes), serum immunoglobulins (IgA, IgG, IgM), liver antioxidants (CAT, GSH-PX, SOD), splenic cytokines (IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IFN-γ, TNF-α), immune organ histopathology, immune function (ear swelling, carbon clearance), splenic NF-κB/MAPK gene expression, gut microbiota, and short-chain fatty acids (SCFAs).

RESULTS

Heat-inactivated A. muciniphila significantly reversed CTX-induced weight loss, hematological abnormalities, reduced immunoglobulins, and immune organ damage. It enhanced liver antioxidant activity and restored immune function (increased ear swelling, improved carbon clearance). Cytokine imbalances were corrected: suppressed cytokines (IL-1β, IL-2, IL-6, TNF-α) increased, while elevated ones (IL-4, IL-8, IFN-γ) decreased. The treatment downregulated overactivated splenic NF-κB/MAPK signaling. Gut dysbiosis was ameliorated via reduced Bacteroidota/Bacillota ratio and enrichment of beneficial taxa (e.g., o_Clostridia_UCG-014). Reduced SCFAs, particularly propanoic and isovaleric acid, were replenished.

CONCLUSIONS

In conclusion, heat-inactivated A. muciniphila AKK PROBIO effectively counteracts CTX-induced immunosuppression through multi-faceted mechanisms involving immune restoration, antioxidant enhancement, NF-κB/MAPK pathway regulation, and gut microbiota correction, highlighting its promise as a safe postbiotic therapeutic agent.