Salt-responsive gut commensal modulates TH17 axis and disease

被引：1202

作者：

Wilck, Nicola ^{[1
,2
,3
,4
,5
,6
]}

Matus, Mariana G. ^{[7
,8
,9
]}

Kearney, Sean M. ^{[7
,8
]}

Olesen, Scott W. ^{[7
,8
]}

Forslund, Kristoffer ^{[10
]}

Bartolomaeus, Hendrik ^{[1
,2
,3
,4
,5
,6
]}

Haase, Stefanie ^{[11
]}

Maehler, Anja ^{[1
,2
]}

Balogh, Andras ^{[1
,2
,3
,4
,5
,6
]}

Marko, Lajos ^{[3
,4
,5
,6
]}

Vedenskaya, Olga V. ^{[4
,12
,13
]}

Kleiner, Friedrich H. ^{[1
,2
]}

Tsvetkov, Dmitry ^{[1
,2
,3
]}

Klug, Lars

Costea, Paul I. ^{[10
]}

Sunagawa, Shinichi ^{[10
,14
]}

Maier, Lisa ^{[15
]}

Rakova, Natalia ^{[1
,2
]}

Schatz, Valentin ^{[16
]}

Neubert, Patrick ^{[16
]}

Fraetzer, Christian ^{[17
]}

Krannich, Alexander

Gollasch, Maik ^{[1
,2
,3
,4
]}

Grohme, Diana A. ^{[18
]}

Corte-Real, Beatriz F. ^{[19
]}

Gerlach, Roman G. ^{[20
]}

Basic, Marijana ^{[21
,22
]}

Typas, Athanasios

Wu, Chuan ^{[23
]}

Titze, Jens M. ^{[24
]}

Jantsch, Jonathan

Boschmann, Michael ^{[1
,2
]}

Dechend, Ralf ^{[1
,2
,3
,4
]}

Kleinewietfeld, Markus ^{[25
]}

Kempa, Stefan ^{[4
,12
]}

Bork, Peer ^{[4
,26
,27
]}

Linker, Ralf A.

Alm, Eric J. ^{[7
,8
]}

Mueller, Dominik N. ^{[1
,2
,3
,4
,5
,6
]}

机构：

[1] Max Delbruck Ctr Mol Med, Expt & Clin Res Ctr, D-13125 Berlin, Germany

[2] Charite Univ Med Berlin, D-13125 Berlin, Germany

[3] Charite Univ Med Berlin, D-10117 Berlin, Germany

[4] Max Delbruck Ctr Mol Med, Helmholtz Assoc, D-13125 Berlin, Germany

[5] DZHK German Ctr Cardiovasc Res, Partner Site Berlin, Berlin, Germany

[6] BIH, Berlin, Germany

[7] MIT, Ctr Microbiome Informat & Therapeut, Cambridge, MA 02139 USA

[8] MIT, Dept Biol Engn, Cambridge, MA 02139 USA

[9] MIT, Computat & Syst Biol Program, Cambridge, MA 02139 USA

[10] European Mol Biol Lab, Struct & Computat Biol Unit, D-69117 Heidelberg, Germany

[11] Friedrich Alexander Univ Erlangen Nuremberg, Dept Neurol, D-91054 Erlangen, Germany

[12] Inst Med Syst Biol BIMSB, Integrat Prote & Metabol Platform, D-13125 Berlin, Germany

[13] Charite Univ Med Berlin, Berlin Sch Integrat Oncol, Berlin, Germany

[14] Swiss Fed Inst Technol, Inst Microbiol, CH-8092 Zurich, Switzerland

[15] European Mol Biol Lab, Genome Biol Unit, D-69117 Heidelberg, Germany

[16] Univ Regensburg, Univ Hosp Regensburg, Inst Clin Microbiol & Hyg, D-93053 Regensburg, Germany

[17] Lipidomix GmbH, D-13125 Berlin, Germany

[18] Tech Univ Dresden, Med Fac Carl Gustav Carus, Dept Clin Pathobiochem, Translat Immunol, D-01307 Dresden, Germany

[19] Hasselt Univ, VIB Ctr Inflammat Res IRC, VIB Lab Translat Immunomodulat, Campus Diepenbeek, B-3590 Diepenbeek, Belgium

[20] Robert Koch Inst, Project Grp 5, D-38855 Wernigerode, Germany

[21] Inst Lab Anim Sci, Hannover Med Sch, D-30625 Hannover, Germany

[22] Cent Anim Facil, D-30625 Hannover, Germany

[23] US Natl Inst Hlth, Natl Canc Inst, Exp Immunol Branch, Bethesda, MD USA

[24] Vanderbilt Univ, Sch Med, Div Clin Pharmacol, Nashville, TN 37212 USA

[25] Ctr Regenerat Therapies Dresden CRTD, D-01307 Dresden, Germany

[26] Heidelberg Univ, Mol Med Partnership Unit, D-69120 Heidelberg, Germany

[27] Univ Wurzburg, Dept Bioinformat, Bioctr, D-970740 Wurzburg, Germany

来源：

NATURE | 2017年 / 551卷 / 7682期

基金：

欧洲研究理事会;

关键词：

ARYL-HYDROCARBON RECEPTOR; II-INDUCED HYPERTENSION; BLOOD-PRESSURE; SODIUM-INTAKE; T-CELL; MICROBIOTA; LACTOBACILLI; COMMUNITY; IMPACT; HOMEOSTASIS;

D O I：

10.1038/nature24628

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

A Western lifestyle with high salt consumption can lead to hypertension and cardiovascular disease. High salt may additionally drive autoimmunity by inducing T helper 17 (T(H)17) cells, which can also contribute to hypertension. Induction of T(H)17 cells depends on gut microbiota; however, the effect of salt on the gut microbiome is unknown. Here we show that high salt intake affects the gut microbiome in mice, particularly by depleting Lactobacillus murinus. Consequently, treatment of mice with L. murinus prevented salt-induced aggravation of actively induced experimental autoimmune encephalomyelitis and salt-sensitive hypertension by modulating T(H)17 cells. In line with these findings, a moderate high-salt challenge in a pilot study in humans reduced intestinal survival of Lactobacillus spp., increased T(H)17 cells and increased blood pressure. Our results connect high salt intake to the gut-immune axis and highlight the gut microbiome as a potential therapeutic target to counteract salt-sensitive conditions.

引用

页码：585 / +

页数：23

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