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 Lähdesmäki, Curtis Huttenhower, Dirk Gevers, Thomas W Cullen, Mikael Knip, DIABIMMUNE Study Group, Ramnik J Xavier, 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 Lähdesmäki, Curtis Huttenhower, Dirk Gevers, Thomas W Cullen, Mikael Knip, DIABIMMUNE Study Group, Ramnik J Xavier
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.
Copyright © 2016 Elsevier Inc. All rights reserved.
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Source: PubMed