Drosophila Histone Demethylase KDM5 Regulates Social Behavior through Immune Control and Gut Microbiota Maintenance

被引：168

作者：

Chen, Kun ^{[1
,2
,3
,4
]}

Luan, Xiaoting ^{[1
]}

Liu, Qisha ^{[1
,2
]}

Wang, Jianwei ^{[1
,2
]}

Chang, Xinxia ^{[1
,2
]}

Snijders, Antoine M. ^{[5
]}

Mao, Jian-Hua ^{[5
]}

Secombe, Julie ^{[6
,7
]}

Dan, Zhou ^{[1
]}

Chen, Jian-Huan ^{[8
]}

Wang, Zibin ^{[9
]}

Dong, Xiao ^{[6
,7
]}

Qiu, Chen ^{[1
]}

Chang, Xiaoai ^{[3
]}

Zhang, Dong ^{[1
]}

Celniker, Susan E. ^{[5
]}

Liu, Xingyin ^{[1
,2
,3
,4
]}

机构：

[1] Nanjing Med Univ, Dept Pathogen Biol, Microbiol Div, State Key Lab Reprod Med, Nanjing 211166, Jiangsu, Peoples R China

[2] Nanjing Med Univ, Ctr Global Hlth, Key Lab Pathogen Jiangsu Prov, Nanjing 211166, Jiangsu, Peoples R China

[3] Nanjing Med Univ, Key Lab Human Funct Genom Jiangsu Prov, Nanjing 211166, Jiangsu, Peoples R China

[4] Nanjing Med Univ, Affiliated Hosp 2, Key Lab Holist Integrat Enterol, Nanjing 210011, Jiangsu, Peoples R China

[5] Lawrence Berkeley Natl Lab, Biol Syst & Engn Div, Berkeley, CA 94720 USA

[6] Albert Einstein Coll Med, Dept Genet, Bronx, NY 10467 USA

[7] Albert Einstein Coll Med, Dept Neurosci, Bronx, NY 10467 USA

[8] Jiangnan Univ, Wuxi Sch Med, Dept Publ Hlth, Genom & Precis Med Lab, Wuxi 214122, Peoples R China

[9] Nanjing Med Univ, Ctr Anal & Testing, Nanjing 211166, Jiangsu, Peoples R China

来源：

CELL HOST & MICROBE | 2019年 / 25卷 / 04期

基金：

中国国家自然科学基金; 美国国家卫生研究院;

关键词：

INTELLECTUAL DISABILITY; MUTATIONS; MODEL; PGRP; HOMEOSTASIS; EXPRESSION; LOCOMOTION; RESPONSES; RECEPTOR;

D O I：

10.1016/j.chom.2019.02.003

中图分类号：

Q93 [微生物学];

学科分类号：

071005 [微生物学];

摘要：

Loss-of-function mutations in the histone demethylases KDM5A, KDM5B, or KDM5C are found in intellectual disability (ID) and autism spectrum disorders (ASD) patients. Here, we use the model organism Drosophilamelanogaster to delineate how KDM5 contributes to ID and ASD. We show that reducing KDM5 causes intestinal barrier dysfunction and changes in social behavior that correlates with compositional changes in the gut microbiota. Therapeutic alteration of the dysbiotic microbiota through antibiotic administration or feeding with a probiotic Lactobacillus strain partially rescues the behavioral, lifespan, and cellular phenotypes observed in kdm5-deficient flies. Mechanistically, KDM5 was found to transcriptionally regulate component genes of the immune deficiency (IMD) signaling pathway and subsequent maintenance of host-commensal bacteria homeostasis in a demethylase-dependent manner. Together, our study uses a genetic approach to dissect the role of KDM5 in the gut-microbiome-brain axis and suggests that modifying the gut microbiome may provide therapeutic benefits for ID and ASD patients.

引用

页码：537 / +

页数：24

共 62 条

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