The microbiome and immunodeficiencies: Lessons from rare diseases

Area of Science:

• Immunology
• Microbiology
• Genetics

Background:

• Primary immunodeficiencies (PIDs) are inherited immune system disorders.
• PIDs increase susceptibility to infections, malignancy, inflammation, and autoimmunity.
• Immune dysregulation in PIDs is increasingly linked to gut microbiota alterations.

Purpose of the Study:

• To review literature on gut microbiota dysbiosis in PIDs.
• To explore the bidirectional relationship between PIDs and gut microbiota.
• To discuss potential therapeutic strategies involving microbiota manipulation.

Main Methods:

• Literature review of studies on PIDs and gut microbiota.
• Analysis of mechanisms linking genetic defects to gut barrier dysfunction.
• Examination of preclinical models for microbiota-targeted interventions.

Main Results:

• Genetic defects in PIDs disrupt gut homeostasis, leading to increased permeability and bacterial translocation.
• Dysbiosis is prevalent in PIDs, potentially causing or resulting from immune dysregulation.
• Infections exacerbate pathobiont colonization, increasing disease susceptibility.

Conclusions:

• Gut microbiota plays a significant role in the pathogenesis and complications of PIDs.
• Targeting gut microbiota through dietary interventions or other methods shows promise for managing PIDs.
• Further research into the PID-microbiota axis is crucial for developing novel therapies.