Variation in Microbiome LPS Immunogenicity Contributes to Autoimmunity in Humans

Area of Science:

• Immunology
• Microbiology
• Environmental Health

Background:

• The hygiene hypothesis posits that reduced microbial exposure in early life alters immune maturation, potentially increasing autoimmune disease incidence.
• Autoimmune diseases are more prevalent in Westernized countries, suggesting environmental factors, like gut microbiome composition, play a role.

Purpose of the Study:

• To investigate the relationship between gut microbiome development in infancy and the prevalence of autoimmune diseases.
• To compare gut microbiome composition in infants from Northern European regions with differing autoimmune disease rates (Finland, Estonia, Russia).

Main Methods:

• Longitudinal study of gut microbiome development in 222 infants from birth to age three.
• Analysis of lipopolysaccharide (LPS) exposure from dominant gut bacteria, specifically Bacteroides and Escherichia coli.
• Assessment of LPS effects on innate immune signaling and in a mouse model of autoimmune diabetes.

Main Results:

• Bacteroides species were abundant in Finnish and Estonian infants but scarce in Russian infants.
• Infants from Finland and Estonia had higher lipopolysaccharide (LPS) exposure from Bacteroides, unlike Russian infants who had more exposure from Escherichia coli.
• Bacteroides LPS exhibited distinct structural and functional properties compared to E. coli LPS, inhibiting innate immune signaling and failing to protect against autoimmune diabetes in mice.

Conclusions:

• Early gut colonization by immunologically silencing microbiota, such as Bacteroides, may influence immune education.
• Differences in early microbial exposure, specifically LPS from Bacteroides versus E. coli, could contribute to varying autoimmune disease incidence.