Variation in Microbiome LPS Immunogenicity Contributes to Autoimmunity in Humans

Tommi Vatanen, Aleksandar D. Kostic, Eva D'Hennezel, Heli Siljander, Eric A. Franzosa, Moran Yassour, Raivo Kolde, Hera Vlamakis, Timothy D. Arthur, Anu Maaria Hämäläinen, Aleksandr Peet, Vallo Tillmann, Raivo Uibo, Sergei Mokurov, Natalya Dorshakova, Jorma Ilonen, Suvi M. Virtanen, Susanne J. Szabo, Jeffrey A. Porter, Harri LähdesmäkiCurtis Huttenhower, Dirk Gevers, Thomas W. Cullen, Mikael Knip, Ramnik J. Xavier*

*Corresponding author for this work

Research output: Contribution to journalArticleScientificpeer-review

426 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)842-853
Number of pages12
JournalCELL
Volume165
Issue number4
DOIs
Publication statusPublished - 5 May 2016
MoE publication typeA1 Journal article-refereed

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