A1 Refereed original research article in a scientific journal
Variation in Microbiome LPS Immunogenicity Contributes to Autoimmunity in Humans
Authors: Tommi Vatanen, Aleksandar D. Kostic, Eva d'Hennezel, Heli Siljander, Eric A. Franzosa, Moran Yassour, Raivo Kolde, Hera Vlamakis, Timothy D. Arthur, Anu-Maaria Hämälainen, Aleksandr Peet, Vallo Tillmann, Raivo Uibo, Sergei Mokurov, Natalya Dorshakova, Jorma Ilonen, Suvi M. Virtanen, Susanne Szabo, Jeffrey A. Porter, Harri Lähdesmäki, Curtis Huttenhower, Dirk Gevers, Tomas W. Cullen, Mikael Knip, Ramnik J. Xavier
Publisher: CELL PRESS
Publication year: 2016
Journal: Cell
Journal name in source: CELL
Journal acronym: CELL
Volume: 165
Issue: 4
First page : 842
Last page: 853
Number of pages: 12
ISSN: 0092-8674
DOI: https://doi.org/10.1016/j.cell.2016.04.007
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.
