Immunosuppressant imprecision: multidirectional effects on metabolism and microbiome

Area of Science:

• Immunology
• Microbiology
• Metabolic Science

Background:

• Transplant recipients need lifelong immunosuppression to prevent organ rejection.
• Current immunosuppressants lack antigen specificity, leading to chronic inflammation, scarring, and graft failure.
• These drugs also cause gut dysbiosis and metabolic disorders.

Purpose of the Study:

• To review the impact of immunosuppressant treatments on alloimmunity, gut microbiome, and metabolism.
• To emphasize the specific effects on metabolic disorders.
• To identify microbial and metabolic signatures associated with different immunosuppressant classes.

Main Methods:

• Literature review of immunosuppressant effects.
• Analysis of impacts on alloimmunity, gut microbiome, and host metabolism.
• Characterization of drug-specific microbial and metabolic signatures.

Main Results:

• Immunosuppressants broadly affect alloimmunity, gut microbiome, and metabolism.
• Distinct microbial and metabolic profiles are associated with different immunosuppressant classes.
• These effects contribute to metabolic disorders and potentially graft dysfunction.

Conclusions:

• A comprehensive understanding of immunosuppressants' on- and off-target effects is crucial.
• Targeting the gut microbiome and host metabolism may optimize immunosuppressive therapy.
• This approach could enhance immunosuppression efficacy, graft acceptance, and patient survival.