The gut microbiota mediates protective immunity against tuberculosis via modulation of lncRNA
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...
| Main Authors: | , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2022-12-01
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| Series: | Gut Microbes |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/19490976.2022.2029997 |
| _version_ | 1819159746302705664 |
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| author | Fang Yang Yi Yang Lingming Chen Zhiyi Zhang Linna Liu Chunmin Zhang Qiongdan Mai Yiwei Chen Zixu Chen Tao Lin Liang Chen Huixin Guo Lin Zhou Hongbo Shen Xinchun Chen Lei Liu Guoliang Zhang Hongying Liao Lingchan Zeng Gucheng Zeng |
| author_facet | Fang Yang Yi Yang Lingming Chen Zhiyi Zhang Linna Liu Chunmin Zhang Qiongdan Mai Yiwei Chen Zixu Chen Tao Lin Liang Chen Huixin Guo Lin Zhou Hongbo Shen Xinchun Chen Lei Liu Guoliang Zhang Hongying Liao Lingchan Zeng Gucheng Zeng |
| author_sort | Fang Yang |
| collection | DOAJ |
| description | 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-γ 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-γ 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. |
| first_indexed | 2024-12-22T16:45:27Z |
| format | Article |
| id | doaj.art-e58f4145df79420387cb7050d04a1b1c |
| institution | Directory Open Access Journal |
| issn | 1949-0976 1949-0984 |
| language | English |
| last_indexed | 2024-12-22T16:45:27Z |
| publishDate | 2022-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Gut Microbes |
| spelling | doaj.art-e58f4145df79420387cb7050d04a1b1c2022-12-21T18:19:45ZengTaylor & Francis GroupGut Microbes1949-09761949-09842022-12-0114110.1080/19490976.2022.2029997The gut microbiota mediates protective immunity against tuberculosis via modulation of lncRNAFang Yang0Yi Yang1Lingming Chen2Zhiyi Zhang3Linna Liu4Chunmin Zhang5Qiongdan Mai6Yiwei Chen7Zixu Chen8Tao Lin9Liang Chen10Huixin Guo11Lin Zhou12Hongbo Shen13Xinchun Chen14Lei Liu15Guoliang Zhang16Hongying Liao17Lingchan Zeng18Gucheng Zeng19Department of Microbiology Zhongshan School of Medicine, Key Laboratory for Tropical Diseases Control of the Ministry of Education, Sun Yat-sen University, Guangzhou ChinaDepartment of Microbiology Zhongshan School of Medicine, Key Laboratory for Tropical Diseases Control of the Ministry of Education, Sun Yat-sen University, Guangzhou ChinaDepartment of Microbiology Zhongshan School of Medicine, Key Laboratory for Tropical Diseases Control of the Ministry of Education, Sun Yat-sen University, Guangzhou ChinaDepartment of Microbiology Zhongshan School of Medicine, Key Laboratory for Tropical Diseases Control of the Ministry of Education, Sun Yat-sen University, Guangzhou ChinaDepartment of Microbiology Zhongshan School of Medicine, Key Laboratory for Tropical Diseases Control of the Ministry of Education, Sun Yat-sen University, Guangzhou ChinaDrepartment of Pediatric Intensive Care Unit, Guangzhou Women and Children’s Medical Center, Picu, Guangzhou ChinaDepartment of Microbiology Zhongshan School of Medicine, Key Laboratory for Tropical Diseases Control of the Ministry of Education, Sun Yat-sen University, Guangzhou ChinaDepartment of Microbiology Zhongshan School of Medicine, Key Laboratory for Tropical Diseases Control of the Ministry of Education, Sun Yat-sen University, Guangzhou ChinaDepartment of Microbiology Zhongshan School of Medicine, Key Laboratory for Tropical Diseases Control of the Ministry of Education, Sun Yat-sen University, Guangzhou ChinaDepartment of Microbiology Zhongshan School of Medicine, Key Laboratory for Tropical Diseases Control of the Ministry of Education, Sun Yat-sen University, Guangzhou ChinaGuangdong Center for Tuberculosis Control, National Clinical Research Center for Tuberculosis, Guangzhou ChinaGuangdong Center for Tuberculosis Control, National Clinical Research Center for Tuberculosis, Guangzhou ChinaGuangdong Center for Tuberculosis Control, National Clinical Research Center for Tuberculosis, Guangzhou ChinaClinic and Research Center of Tuberculosis, Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Institute for Advanced Study, Tongji University School of Medicine, Shanghai, ChinaDepartment of Pathogen Biology, Shenzhen University School of Medicine, Shenzhen, Guangdong ChinaInstitute for Hepatology, National Clinical Research Center for Infectious Disease, Guangdong Key Laboratory for Emerging Infectious Diseases, Shenzhen Third People’s Hospital, National Clinical Research Center for Tuberculosis, Southern University of Science and Technology, National Clinical Research Center for Tuberculosis, Shenzhen, ChinaInstitute for Hepatology, National Clinical Research Center for Infectious Disease, Guangdong Key Laboratory for Emerging Infectious Diseases, Shenzhen Third People’s Hospital, National Clinical Research Center for Tuberculosis, Southern University of Science and Technology, National Clinical Research Center for Tuberculosis, Shenzhen, ChinaDe partment of Thoracic Surgery, Thoracic Cancer Center, the Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, ChinaClinical Research Center, Department of Medical Records Management, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong, ChinaDepartment of Microbiology Zhongshan School of Medicine, Key Laboratory for Tropical Diseases Control of the Ministry of Education, Sun Yat-sen University, Guangzhou ChinaThe 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-γ 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-γ 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.https://www.tandfonline.com/doi/10.1080/19490976.2022.2029997Tuberculosisgut-lung axiscommensal gut bacteria |
| spellingShingle | Fang Yang Yi Yang Lingming Chen Zhiyi Zhang Linna Liu Chunmin Zhang Qiongdan Mai Yiwei Chen Zixu Chen Tao Lin Liang Chen Huixin Guo Lin Zhou Hongbo Shen Xinchun Chen Lei Liu Guoliang Zhang Hongying Liao Lingchan Zeng Gucheng Zeng The gut microbiota mediates protective immunity against tuberculosis via modulation of lncRNA Gut Microbes Tuberculosis gut-lung axis commensal gut bacteria |
| title | The gut microbiota mediates protective immunity against tuberculosis via modulation of lncRNA |
| title_full | The gut microbiota mediates protective immunity against tuberculosis via modulation of lncRNA |
| title_fullStr | The gut microbiota mediates protective immunity against tuberculosis via modulation of lncRNA |
| title_full_unstemmed | The gut microbiota mediates protective immunity against tuberculosis via modulation of lncRNA |
| title_short | The gut microbiota mediates protective immunity against tuberculosis via modulation of lncRNA |
| title_sort | gut microbiota mediates protective immunity against tuberculosis via modulation of lncrna |
| topic | Tuberculosis gut-lung axis commensal gut bacteria |
| url | https://www.tandfonline.com/doi/10.1080/19490976.2022.2029997 |
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