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Heat-inactivated Akkermansia muciniphila AKK-PROBIO ameliorates cyclophosphamide-induced immunosuppression via the
Linglan Suo1, Rao Li1, Menghe Chen1
1College of Food Science and Engineering, Jilin Agricultural University, Changchun, Jilin Province, 130118, People's Republic of China.
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.
Insights
Heat-inactivated Akkermansia muciniphila AKK PROBIO effectively combats immune suppression caused by cyclophosphamide (CTX) in mice. This postbiotic restores immune function, enhances antioxidant capacity, and improves gut health.
Area of Science:
- Immunology
- Microbiology
- Pharmacology
Background:
- Immune dysfunction is implicated in various diseases.
- Akkermansia muciniphila shows immunomodulatory effects, but its heat-inactivated form's efficacy is not fully understood.
Purpose of the Study:
- To investigate the effects of oral heat-inactivated A. muciniphila AKK PROBIO on cyclophosphamide (CTX)-induced immunosuppression in mice.
- To elucidate the underlying mechanisms of action.
Main Methods:
- Mice received CTX followed by oral heat-inactivated A. muciniphila for 14 days.
- Comprehensive analyses included hematology, serum immunoglobulins, liver antioxidants, splenic cytokines, immune organ histopathology, immune function tests, gene expression (NF-κB/MAPK), gut microbiota, and short-chain fatty acids (SCFAs).
Main Results:
- Heat-inactivated A. muciniphila reversed CTX-induced immunosuppression, improving weight, hematology, and immune organ health.
- The treatment enhanced antioxidant activity, restored immune function, corrected cytokine imbalances, and downregulated splenic NF-κB/MAPK signaling.
- Gut dysbiosis was ameliorated, with restoration of beneficial bacteria and replenishment of short-chain fatty acids (SCFAs).
Conclusions:
- Heat-inactivated A. muciniphila AKK PROBIO effectively counteracts CTX-induced immunosuppression via immune restoration, antioxidant enhancement, and gut microbiota modulation.
- This study highlights the potential of heat-inactivated A. muciniphila as a safe postbiotic therapeutic agent for immune dysfunction.
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