Cell
Volume 165, Issue 4, 5 May 2016, Pages 842-853
Journal home page for Cell

Article
Variation in Microbiome LPS Immunogenicity Contributes to Autoimmunity in Humans

https://doi.org/10.1016/j.cell.2016.04.007Get rights and content
Under an Elsevier user license
open archive

Highlights

  • Finnish and Estonian infants have a distinct early gut microbiome compared to Russians

  • B. dorei and other Bacteroides species are highly abundant in Finland and Estonia

  • B. dorei LPS inhibits the immunostimulatory activity of E. coli LPS

  • LPS from B. dorei does not protect NOD mice from type 1 diabetes

Summary

According to the hygiene hypothesis, the increasing incidence of autoimmune diseases in western countries may be explained by changes in early microbial exposure, leading to altered immune maturation. We followed gut microbiome development from birth until age three in 222 infants in Northern Europe, where early-onset autoimmune diseases are common in Finland and Estonia but are less prevalent in Russia. We found that Bacteroides species are lowly abundant in Russians but dominate in Finnish and Estonian infants. Therefore, their lipopolysaccharide (LPS) exposures arose primarily from Bacteroides rather than from Escherichia coli, which is a potent innate immune activator. We show that Bacteroides LPS is structurally distinct from E. coli LPS and inhibits innate immune signaling and endotoxin tolerance; furthermore, unlike LPS from E. coli, B. dorei LPS does not decrease incidence of autoimmune diabetes in non-obese diabetic mice. Early colonization by immunologically silencing microbiota may thus preclude aspects of immune education.

Cited by (0)

22

Co-first author

23

Co-senior author