Variation in Microbiome LPS Immunogenicity Contributes to Autoimmunity in Humans

被引：848

作者：

Vatanen, Tommi ^{[1
,2
]}

Kostic, Aleksandar D. ^{[1
,3
,4
,5
]}

d'Hennezel, Eva ^{[6
]}

Siljander, Heli ^{[7
,8
,9
,10
]}

Franzosa, Eric A. ^{[1
,5
]}

Yassour, Moran ^{[1
]}

Kolde, Raivo ^{[3
,4
]}

Vlamakis, Hera ^{[1
]}

Arthur, Timothy D. ^{[1
]}

Hamalainen, Anu-Maaria ^{[11
]}

Peet, Aleksandr ^{[12
,13
]}

Tillmann, Vallo ^{[12
,13
]}

Uibo, Raivo ^{[14
]}

Mokurov, Sergei ^{[15
]}

Dorshakova, Natalya ^{[16
]}

Ilonen, Jorma ^{[17
,18
]}

Virtanen, Suvi M. ^{[19
,20
,21
,22
]}

Szabo, Susanne J. ^{[6
]}

Porter, Jeffrey A. ^{[6
]}

Lahdesmaki, Harri ^{[2
]}

Huttenhower, Curtis ^{[1
,5
]}

Gevers, Dirk ^{[1
]}

Cullen, Thomas W. ^{[6
]}

Knip, Mikael ^{[7
,8
,9
,10
,23
]}

Xavier, Ramnik J. ^{[1
,3
,4
,24
,25
,26
,27
]}

机构：

[1] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA

[2] Aalto Univ, Dept Comp Sci, Sch Sci, Espoo 02150, Finland

[3] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA

[4] Harvard Univ, Sch Med, Boston, MA 02114 USA

[5] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA

[6] Novartis Inst Biomed Res Inc, Cambridge, MA 02139 USA

[7] Univ Helsinki, Childrens Hosp, Stenbackinkatu 11, FIN-00290 Helsinki, Finland

[8] Helsinki Univ Hosp, Helsinki 00290, Finland

[9] Univ Helsinki, Res Programs Unit, Diabet & Obes Res Program, FIN-00290 Helsinki, Finland

[10] Tampere Univ Hosp, Dept Pediat, Tampere 33521, Finland

[11] Helsinki Univ Hosp, Jorvi Hosp, Dept Pediat, Espoo 02740, Finland

[12] Univ Tartu, Dept Pediat, Tartu 51014, Estonia

[13] Tartu Univ Hosp, Tartu 51014, Estonia

[14] Univ Tartu, Ctr Excellence Translat Med, Inst Biomed & Translat Med, Dept Immunol, Tartu 50411, Estonia

[15] Minist Hlth & Social Dev, Lenin St 6, Petrozavodsk 185035, Russia

[16] Petrozavodsk State Univ, Dept Family Med, Lenin St 33, Petrozavodsk 185910, Russia

[17] Univ Turku, Immunogenet Lab, FIN-20520 Turku, Finland

[18] Univ Eastern Finland, Dept Clin Microbiol, Kuopio 70211, Finland

[19] Natl Inst Hlth & Welf, Dept Hlth, Helsinki 00271, Finland

[20] Univ Tampere, Sch Hlth Sci, Tampere 33014, Finland

[21] Tampere Univ Hosp, Pirkanmaa Hosp Dist, Sci Ctr, Tampere 33521, Finland

[22] Tampere Univ Hosp, Res Ctr Child Hlth, Sci Ctr, Tampere 33521, Finland

[23] Folkhalsan Res Ctr, Helsinki 00290, Finland

[24] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA

[25] Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA

[26] Harvard Univ, Sch Med, Boston, MA 02114 USA

[27] MIT, Ctr Microbiome Informat & Therapeut, 77 Massachusetts Ave, Cambridge, MA 02139 USA

来源：

CELL | 2016年 / 165卷 / 04期

基金：

芬兰科学院;

关键词：

INFANT GUT MICROBIOME; MILK OLIGOSACCHARIDES; NEWBORN-INFANTS; RUSSIAN KARELIA; CELIAC-DISEASE; LIPOPOLYSACCHARIDE; SENSITIZATION; CHILDREN; SUSCEPTIBILITY; REACTIVITY;

D O I：

10.1016/j.cell.2016.04.007

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：842 / 853

页数：12

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