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Cell DOI:10.1016/j.cell.2016.04.007

Variation in Microbiome LPS Immunogenicity Contributes to Autoimmunity in Humans.

Publication TypeJournal Article
Year of Publication2016
AuthorsVatanen, T, Kostic, AD, d'Hennezel, E, Siljander, H, Franzosa, EA, Yassour, M, Kolde, R, Vlamakis, H, Arthur, TD, Hämäläinen, A-M, Peet, A, Tillmann, V, Uibo, R, Mokurov, S, Dorshakova, N, Ilonen, J, Virtanen, SM, Szabo, SJ, Porter, JA, Lähdesmäki, H, Huttenhower, C, Gevers, D, Cullen, TW, Knip, M, Xavier, RJ
Corporate AuthorsDIABIMMUNE Study Group
Date Published2016 May 05
KeywordsAnimals, Bacteroides, Diabetes Mellitus, Type 1, Estonia, Feces, Finland, Food Microbiology, Gastrointestinal Microbiome, Humans, Infant, Lipopolysaccharides, Mice, Mice, Inbred NOD, Milk, Human, Russia

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.


Alternate JournalCell
PubMed ID27133167
PubMed Central IDPMC4950857
Grant ListP30 DK043351 / DK / NIDDK NIH HHS / United States
R01 DK092405 / DK / NIDDK NIH HHS / United States
U54 DK102557 / DK / NIDDK NIH HHS / United States