Epigenetic regulation by gut microbiota

Woo, Vivienne; Alenghat, Theresa

doi:10.1080/19490976.2021.2022407

Cited by 155 publications

(124 citation statements)

References 112 publications

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“…Recently, Ansari et al reported that commensal microbiota induced Tet2/3-dependent DNA methylation at regulatory elements of 'early sentinel' response genes, which is critical for maintaining intestinal homeostasis [70]. Our ndings extend this notion by revealing that Tet2-driven epigenetic regulation, tuned by gut microbiome, have an important role in remotely regulating pulmonary immune response [71].…”

Section: Discussionsupporting

confidence: 77%

Gut microbial GABAergic signaling imprints alveolar macrophages and pulmonary response to viral infection associated with psychological stress

Gao

Liang

Mao

et al. 2022

Preprint

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Background Epidemiological evidences reveal that populations with psychological stress have an increased likelihood of respiratory viral infection involving influenza A virus (IAV) and SARS-CoV-2, but the mechanism remains elusive. Results By exploiting a chronic restraint stress (CRS) mouse model, we demonstrated that psychiatric stress substantially increased hosts’ vulnerability to viral pneumonia, concurrent with deregulated alveolar macrophages (AMs) and disturbed gut microbiome. The central importance of gut microbiome in stress-exacerbated viral pneumonia was confirmed by microbiome depletion and gut microbiome transplantation. In particular, stress exposure induced a decline in Lactobacillaceae abundance and hence γ-aminobutyric acid (GABA) level in mice. Microbial-derived GABA proved to be released in the peripheral and sensed by AMs via GABAAR, leading to enhanced mitochondrial metabolism and α-ketoglutarate (αKG) generation. The metabolic intermediator in turn served as the cofactor for the epigenetic regulator Tet2 to catalyze DNA hydroxymethylation, and promoted PPARγ-centered gene program underpinning survival, self-renewing, and immunoregulation of AMs. We thus uncover an unappreciated GABA/Tet2/PPARγ regulatory circuitry that was initiated by gut microbiome to instruct distant immune cells through a metabolic-epigenetic program. Accordingly, reconstitution with GABA-producing probiotics, or adoptive transferring of GABA-conditioned AMs, or resumption of pulmonary αKG level remarkably improved AMs homeostasis and alleviated severe pneumonia in stressed mice. Conclusions Together, our study identifies a microbiome-derived tonic signaling that is tuned by mental health status to imprint resident immune cells and defensive response in lungs. The findings are particularly significant for the subpopulation with psychiatric stress to combat critical respiratory viral infection.

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Section: Discussionsupporting

confidence: 77%

Gut microbial GABAergic signaling imprints alveolar macrophages and pulmonary response to viral infection associated with psychological stress

Gao

Liang

Mao

et al. 2022

Preprint

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“…Epigenetic changes related to the gut microbiome include modifications to DNA or histones, as well as the regulation of non-coding RNAs [ 148 ]. For example, recent studies have shown that microorganisms can bind to lysine on histones and regulate host chromatin by modifying histone proteins [ 149 ]. In turn, post-translational modifications of histones induced by microorganisms lead to changes in transcriptional gene activity [ 150 , 151 ].…”

Section: Epigenetic Modificationsmentioning

confidence: 99%

Dysbiosis in Inflammatory Bowel Disease: Pathogenic Role and Potential Therapeutic Targets

Santana

Rosas

Ribeiro

et al. 2022

IJMS

138

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Microbe–host communication is essential to maintain vital functions of a healthy host, and its disruption has been associated with several diseases, including Crohn’s disease and ulcerative colitis, the two major forms of inflammatory bowel disease (IBD). Although individual members of the intestinal microbiota have been associated with experimental IBD, identifying microorganisms that affect disease susceptibility and phenotypes in humans remains a considerable challenge. Currently, the lack of a definition between what is healthy and what is a dysbiotic gut microbiome limits research. Nevertheless, although clear proof-of-concept of causality is still lacking, there is an increasingly evident need to understand the microbial basis of IBD at the microbial strain, genomic, epigenomic, and functional levels and in specific clinical contexts. Recent information on the role of diet and novel environmental risk factors affecting the gut microbiome has direct implications for the immune response that impacts the development of IBD. The complexity of IBD pathogenesis, involving multiple distinct elements, suggests the need for an integrative approach, likely utilizing computational modeling of molecular datasets to identify more specific therapeutic targets.

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“…Microbiota is additional suppliers of methyl and acetyl needed by these epigenetic enzymes to perform their catalytic functions. Metabolic degradation of folate by microbiota produces the main substrate for DNA and histone methylation known as S-adenosylmethionine [ 106 ]. Therefore, the data provided here suggest that the relationship between microbiota and epigenetic regulation may prognosticate carcinogenesis in MM.…”

Section: Host Microbiome and Epigenetic Regulationmentioning

confidence: 99%

Microbiomes, Epigenomics, Immune Response, and Splicing Signatures Interplay: Potential Use of Combination of Regulatory Pathways as Targets for Malignant Mesothelioma

Damane

Mkhize‐Kwitshana

Mehrotra³

et al. 2022

IJMS

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Malignant mesotheliomas (MM) are hard to treat malignancies with poor prognosis and high mortality rates. This cancer is highly misdiagnosed in Sub-Saharan African countries. According to literature, the incidence of MM is likely to increase particularly in low-middle-income countries (LMICs). The burden of asbestos-induced diseases was estimated to be about 231,000 per annum. Lack of awareness and implementation of regulatory frameworks to control exposure to asbestos fibers contributes to the expected increase. Exposure to asbestos fibers can lead to cancer initiation by several mechanisms. Asbestos-induced epigenetic modifications of gene expression machinery and non-coding RNAs promote cancer initiation and progression. Furthermore, microbiome–epigenetic interactions control the innate and adaptive immunity causing exacerbation of cancer progression and therapeutic resistance. This review discusses epigenetic mechanisms with more focus on miRNAs and their interaction with the microbiome. The potential use of epigenetic alterations and microbiota as specific biomarkers to aid in the early detection and/or development of therapeutic targets is explored. The advancement of combinatorial therapies to prolong overall patient survival or possible eradication of MM especially if it is detected early is discussed.

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Epigenetic regulation by gut microbiota

Cited by 155 publications

References 112 publications

Gut microbial GABAergic signaling imprints alveolar macrophages and pulmonary response to viral infection associated with psychological stress

Gut microbial GABAergic signaling imprints alveolar macrophages and pulmonary response to viral infection associated with psychological stress

Dysbiosis in Inflammatory Bowel Disease: Pathogenic Role and Potential Therapeutic Targets

Microbiomes, Epigenomics, Immune Response, and Splicing Signatures Interplay: Potential Use of Combination of Regulatory Pathways as Targets for Malignant Mesothelioma

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