Dataset Information

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

ABSTRACT: 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.

SUBMITTER: Yang F

PROVIDER: S-EPMC8966992 | biostudies-literature | 2022 Jan-Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Yang Fang F Yang Yi Y Chen Lingming L Zhang Zhiyi Z Liu Linna L Zhang Chunmin C Mai Qiongdan Q Chen Yiwei Y Chen Zixu Z Lin Tao T Chen Liang L Guo Huixin H Zhou Lin L Shen Hongbo H Chen Xinchun X Liu Lei L Zhang Guoliang G Liao Hongying H Zeng Lingchan L Zeng Gucheng G

Gut microbes 20220101 1

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< ...[more]

PMID: 35343370

Similar Datasets

Project description:BackgroundBerberine is an isoquinoline alkaloid compound derived from many herbs, which has been used extensively to improve liver function. But action mechanism of its hepatoprotection in alcoholic liver disease (ALD) is far from being clear.AimTo investigate the underlying mechanism of berberine's therapeutic effect on ALD associated with gut microbiota-immune system axis.MethodAn animal model fed with ethanol that mimics drinking pattern ideally in ALD patients was established. Liver function was evaluated by biochemical test and histological examination. Immune cells were detected by flow cytometry and feces samples were collected for 16S rRNA gene amplicon sequencing.ResultsWe first reported the promising beneficial effect of berberine on ameliorating acute-on-chronic alcoholic hepatic damage and explored the underlying mechanism involving gut microbiota-immune system axis. Notably, berberine activated a population with immune suppressive function, defined as granulocytic- myeloid-derived suppressor cell (G-MDSC)-like population, in the liver of mice with alleviating alcohol-induced hepatic injury. Berberine remarkably enhanced the increase of G-MDSC-like cells in blood and liver and decreased cytotoxic T cells correspondingly. Suppression of G-MDSC-like population significantly attenuated the protective effect of berberine against alcohol. Berberine activated IL6/STAT3 signaling in in vitro culture of G-MSDCs-like population, while inhibition of STAT3 activity attenuated the activation of this population by berberine. Moreover, berberine changed the overall gut microbial community, primarily increased the abundance of Akkermansia muciniphila. Of note, depletion of gut microbiota abolished the inducing effect of berberine on G-MDSC-like population, and attenuated its hepatoprotective effect against alcohol in mice, suggesting intestinal flora might be involved in mediating the expansion of this protective population.ConclusionCollectively, this study delivered insight into the role of immunosuppressive response in ALD, and facilitated the understanding of the pharmacological effects and action mechanisms of berberine.

Dataset Information

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

Publications

The gut microbiota mediates protective immunity against tuberculosis <i>via</i> modulation of lncRNA.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets