The gut microbiota mediates protective immunity against tuberculosis via modulation of lncRNA

Yang, Fang1; Yang, Yi1; Chen, Lingming1; Zhang, Zhiyi1; Liu, Linna1; Zhang, Chunmin2; Mai, Qiongdan1; Chen, Yiwei1; Chen, Zixu1; Lin, Tao1; Chen, Liang3; Guo, Huixin3; Zhou, Lin3; Shen, Hongbo4; Chen, Xinchun5; Liu, Lei6; Zhang, Guoliang6; Liao, Hongying7; Zeng, Lingchan8; Zeng, Gucheng1

2022-12-31

10.1080/19490976.2022.2029997

Gut Microbes   影响因子和分区

1949-0976

1949-0984

The gut-lung axis has been implicated as a potential therapeutic target in lung disorders. While increasing evidence suggests that gut microbiota plays a critical role in regulating host immunity and contributing to tuberculosis (TB) development and progression, the underlying mechanisms whereby gut microbiota may impact TB outcomes are not fully understood. Here, we found that broad-spectrum antibiotics treatment increased susceptibility to Mycobacterium tuberculosis (M. tuberculosis) infection and modulated pulmonary inflammatory responses in mouse M. tuberculosis infection model. We then identified a commensal gut bacteria-regulated lncRNA, termed lncRNA-CGB, which was down-regulated by dysbiosis of gut microbiota during TB infection. Furthermore, we found that Bacteroides fragilis (B. fragilis) was a direct regulator of lncRNA-CGB, and oral administration of B. fragilis enhanced expression of lncRNA-CGB and promoted anti-TB immunity. Genomic knock-out of lncRNA-CGB led to reduced IFN-gamma expression and impaired anti-TB immunity, therefore leading to detrimental effects on M. tuberculosis infection. Mechanistically, lncRNA-CGB interacted with EZH2 and negatively regulated H3K27 tri-methylation (H3K27Me3) epigenetic programming, leading to enhanced IFN-gamma expression. Thus, this work not only uncovered previously unrecognized importance of gut bacteria-lncRNA-EZH2-H3K27Me3 axis in conferring immune protection against TB but also identified a potential new paradigm to develop a microbiota-based treatment against TB and potentially other diseases.

Tuberculosis gut-lung axis commensal gut bacteria

SCI

英语

其他

NSFC[82072250] ; National Science and Technology Major Project "Construction of Demonstration Zone for Integrated Prevention and Control of Infectious Diseases"[2018ZX10715004-002-012] ; China Postdoctoral Science Foundation[2017M612811] ; National Key Research and Development Plan["2020YFA0907200","2019YFC0840602"] ; Guangdong Foundation for Basic and Applied Basic Research[2019B1515120041] ; Guangdong Scientific and Technological Foundation[2020B1111170014] ; Shenzhen Scientific and Technological Foundation[KCXFZ202002011007083] ; Shanghai Science and Technology Committee Basic Research[20JC1417800]

Gastroenterology & Hepatology ; Microbiology

Gastroenterology & Hepatology ; Microbiology

WOS:000773727500001

TAYLOR & FRANCIS INC

Web of Science

1.Sun Yat Sen Univ, Dept Microbiol, Key Lab Trop Dis Control, Minist Educ,Zhongshan Sch Med, Guangzhou 510080, Peoples R China
2.Guangzhou Women & Childrens Med Ctr, Drepartment Pediat Intens Care Unit, Guangzhou, Peoples R China
3.Natl Clin Res Ctr TB, Guangdong Ctr TB Control, Guangzhou, Peoples R China
4.Tongji Univ, Shanghai Pulm Hosp, Clin & Res Ctr TB, Inst Adv Study,Sch Med,Shanghai Key Lab TB, Shanghai, Peoples R China
5.Shenzhen Univ, Dept Pathogen Biol, Sch Med, Shenzhen, Guangdong, Peoples R China
6.Southern Univ Sci & Technol, Shenzhen Peoples Hosp 3, Natl Clin Res Ctr Infect Dis, Natl Clin Res Ctr TB,Inst Hepatol,Guangdong Key L, Shenzhen, Peoples R China
7.Sun Yat Sen Univ, Thorac Canc Ctr, Dept Thorac Surg, Affiliated Hosp 6, Guangzhou, Peoples R China
8.Sun Yat Sen Univ, Hosp Stomatol, Clin Res Ctr, Guanghua Sch Stomatol,Dept Med Records Management, Guangzhou, Guangdong, Peoples R China

Yang, Fang,Yang, Yi,Chen, Lingming,et al. The gut microbiota mediates protective immunity against tuberculosis via modulation of lncRNA[J]. Gut Microbes,2022,14(1).

Yang, Fang.,Yang, Yi.,Chen, Lingming.,Zhang, Zhiyi.,Liu, Linna.,...&Zeng, Gucheng.(2022).The gut microbiota mediates protective immunity against tuberculosis via modulation of lncRNA.Gut Microbes,14(1).

Yang, Fang,et al."The gut microbiota mediates protective immunity against tuberculosis via modulation of lncRNA".Gut Microbes 14.1(2022).