Variation in Microbiome LPS Immunogenicity Contributes to Autoimmunity in Humans.

Cell
Authors
Keywords
Abstract

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.

Year of Publication
2016
Journal
Cell
Volume
165
Issue
4
Pages
842-53
Date Published
2016 May 05
ISSN
1097-4172
URL
DOI
10.1016/j.cell.2016.04.007
PubMed ID
27133167
PubMed Central ID
PMC4950857
Links
Grant list
P30 DK043351 / DK / NIDDK NIH HHS / United States
R01 DK092405 / DK / NIDDK NIH HHS / United States
U54 DK102557 / DK / NIDDK NIH HHS / United States