Microbial 'Old Friends', immunoregulation and stress resilience

Area of Science:

• Immunology and Psychiatry
• Microbiome Research
• Public Health Epidemiology

Background:

• Rising prevalence of chronic inflammatory and psychiatric diseases in urban, high-income settings.
• The 'Old Friends' hypothesis suggests reduced exposure to evolutionarily important microbes impairs immunoregulation.
• Inflammation is increasingly recognized as a factor in psychiatric disorders, affecting brain development and mood.

Purpose of the Study:

• To explore the link between diminished exposure to 'Old Friends' microbes and increased risk of inflammatory and psychiatric conditions.
• To investigate how reduced immunoregulation, particularly in early life, interacts with psychosocial stressors.
• To propose novel interpretations of epidemiological data and potential new strategies for addressing psychiatric disease burden.

Main Methods:

• Review and synthesis of epidemiological data on chronic inflammatory and psychiatric diseases in urban vs. rural populations.
• Analysis of the 'hygiene hypothesis' or 'Old Friends' mechanism in the context of modern environmental exposures.
• Conceptual framework integrating immunoregulatory deficits, psychosocial stressors, and microbiota modulation.

Main Results:

• Increased risk for both chronic inflammatory and psychiatric conditions in urban environments and among immigrants.
• Critical disease risk modulation occurs during pregnancy and infancy due to reduced microbial exposures.
• Perinatal 'Old Friends' deficiency may exacerbate psychosocial stress impacts, leading to inflammation and psychiatric symptoms.

Conclusions:

• Reduced exposure to immunoregulation-inducing microbes in early life contributes to poor stress resilience in urban populations.
• The interaction between immunoregulatory deficits and psychosocial stressors is a key factor in modern psychiatric disease.
• This understanding offers new perspectives on disease etiology and potential therapeutic targets.