Gut Microbiota Composition Is Associated with the Global DNA Methylation Pattern in Obesity
Open accessAbstract
Objective: Obesity and obesity-related metabolic diseases are characterized by gut microbiota and epigenetic alterations. Recent insight has suggested the existence of a crosstalk between the gut microbiome and the epigenome. However, the possible link between alterations in gut microbiome composition and epigenetic marks in obesity has been not explored yet. The aim of this work is to establish a link between the gut microbiota and the global DNA methylation profile in a group of obese subjects and to report potential candidate genes that could be epigenetically regulated by gut microbiota in adipose tissue. Methods: Gut microbiota composition was analyzed in DNA stool samples from 45 obese subjects by 16S rRNA gene sequencing. 20 patients were selected based on their Bacteroidetes-to-Firmicutes ratio (BFR): HighBFR group (BFR>2.5, n=10); LowBFR group (BFR<1.2, n=10). Genome-wide analysis of DNA methylation pattern in both whole blood and visceral adipose tissue of these selected patients was performed with an Infinium EPIC BeadChip array-based platform. Gene expression analysis of candidate genes was done in adipose tissue by real-time quantitative PCR. Results: Genome-wide analysis of DNA methylation revealed a completely different DNA methylome pattern in both blood and adipose tissue in the low BFR group vs. the high BFR group. 258 genes were differentially methylated in both blood and adipose tissue, of which several potential candidates were selected for gene expression analysis. We found that in adipose tissue both HDAC7 and IGF2BP2 were hypomethylated and overexpressed in the low BFR group compared to the high BFR group. β values of both genes significantly correlated with the BFR ratio and the relative abundance of Bacteroidetes and/or Firmicutes. Conclusions: In this study we demonstrate that the DNA methylation status is associated to gut microbiota composition in obese subjects, and that the expression levels of candidate genes implicated in glucose and energy ho meostasis (e.g. HDAC7 and IGF2BP2) could be epigenetically regulated by gut bacterial populations in adipose tissue.
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Expression levels of candidate genes implicated in glucose and energy homeostasis (e.g., HDAC7 and IGF2BP2) could be epigenetically regulated by gut bacterial populations.
“Expression levels of candidate genes implicated in glucose and energy homeostasis (e.g., HDAC7 and IGF2BP2) could be epigenetically regulated by gut bacterial populations [159].”
From Food Addiction and Psychosocial Adversity: Biological Embedding, Contextual Factors, and Public Health Implications (2020) · cites this paper as [159]
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A nexus of dietary restriction and gut microbiota: Recent insights into metabolic health
Wang, L., Wang, F., Xiong, L. H., Song, H., Ren, B., & Shen, X. (2023) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2023.2202750 · Cited by 9 · see citing works
Dual Regulation Mechanism of Obesity: DNA Methylation and Intestinal Flora
Ren, Y., Huang, P., Zhang, L., Tang, Y.-F., Luo, S., She, Z., Peng, H., Chen, Y.-Q., Luo, J., Duan, W.-X., et al. (2024) · Biomedicines · doi:10.3390/biomedicines12081633 · Cited by 8 · see citing works
ComputAgeBench: Epigenetic Aging Clocks BenchmarkPreprint
Kriukov, D. V., Efimov, E., Kuzmina, E., Dudkovskaia, A., Khrameeva, E. E., & Dylov, D. V. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.06.06.597715 · Cited by 6 · see citing works
Gut Microbiome Influence on Human Epigenetics, Health, and Disease
Watson, M. M., van der Giezen, M., & Søreide, K. (2022) · Elsevier eBooks · doi:10.1016/b978-0-323-91909-8.00012-8 · Cited by 5 · see citing works
Exploring the Link Between the Gut Microbiota and Epigenetic Factors in Anorexia Nervosa
Korten, N. M., Thelen, A. C., Voelz, C., Beyer, C., Seitz, J., Trinh, S., & Blischke, L. (2025) · Brain and Behavior · doi:10.1002/brb3.70733 · Cited by 4 · see citing works
Alzahrani, S. S. S. (2026) · Frontiers in Microbiology · doi:10.3389/fmicb.2026.1805937 · Cited by 3 · see citing works
Temporal Transcriptomics of Gut Escherichia coli in Caenorhabditis elegans Models of Aging
Brycki, J. D., See, J. R. C., Letson, G. R., Emlet, C., Unverdorben, L. V., Heibeck, N., Brislawn, C., Buonaccorsi, V. P., Chan, J., & Lamendella, R. (2021) · Microbiology Spectrum · doi:10.1128/spectrum.00498-21 · Cited by 2 · see citing works
Woman’s microbiome and obstetrical and perinatal risks: what do they have in common?
Artyomenko, V., Mnikh, L. V., & Domakova, N. V. (2023) · Reproductive health of woman · doi:10.30841/2708-8731.6.2023.289995 · Cited by 3 · see citing works
Epigenomic mechanisms of dietary prescriptions for obesity therapy
Ramos-López, O. (2025) · Epigenomics · doi:10.1080/17501911.2025.2473309 · Cited by 2 · see citing works
Webb, S. J. N., Whitney, S., Yi, S. V., & Simmons, J. H. (2025) · Aging · doi:10.18632/aging.206223 · Cited by 2 · see citing works
Genetic and Epigenetic Regulation by Gut Microbe-Modulated Metabolites in Chronic Metabolic Diseases
Sumi, S., & Kartha, C. C. (2022) · Springer eBooks · doi:10.1007/978-981-16-7672-7_5 · Cited by 1 · see citing works
El‐Daly, S. M., Fayed, B. E., Talaat, R. M., Gouhar, S. A., Fahmy, C. A., El-Jawad, A. M. A., Hamdy, N. Μ., & Elmageed, Z. Y. A. (2026) · Sub-cellular biochemistry/Subcellular biochemistry · doi:10.1007/978-3-032-08530-6_2 · Cited by 1 · see citing works
Epigenetic regulation is involved in reversal of obesity
Rapps, K., Weller, A., & Meiri, N. (2024) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2024.105906 · Cited by 1 · see citing works
Effects of Normal and Cancer Host Tissues on Microbiota Development, Persistence, and Dynamics
Amadei, S. S., & Notario, V. (2021) · Springer eBooks · doi:10.1007/978-3-030-77595-7_20 · Cited by 1 · see citing works
Inflammation and Its Role in Obesity-Related Complications
Singh, M. M., Sharma, J. R., Agraval, H., & Yadav, U. C. S. (2020) · Springer eBooks · doi:10.1007/978-3-030-53370-0_10
Research Progress on the Relationship between Cerebral Infarction and Intestinal Microbiome
杨, 潇. (2021) · Advances in Clinical Medicine · doi:10.12677/acm.2021.117447
Introduction to gut microbiome and epigenetics
Oshinjo, A. M., Michael, O. S., Adedayo, L. D., Adetunji, C. O., Bamidele, O., Adetunji, J. B., Morakinyo, A., Akinwale, E. O., Ajayi, O. O., Awobajo, F. O., et al. (2024) · Elsevier eBooks · doi:10.1016/b978-0-323-91190-0.00009-6
The Epigenetic Impact of the Human Microbiota on Host Cells
Stein, R. A., Cui, R., Faussete, K. C., & Riber, L. (2024) · Springer eBooks · doi:10.1007/978-981-97-3790-1_5
Obesity, gut bacteria, and the epigenetic control of metabolic disease
Guidi, L., Martínez‐Téllez, B., & Santos, C. P. O. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-18979-1.00013-7
Gut Microbiota and Exercise: Implications for Health Promotion and Athletic Performance
Shi, L., Landberg, R., Qu, Y., Lv, J., Zhou, L., Liu, T., Cao, Y., & Wang, D. (2025) · Epigenetics and human health · doi:10.1007/978-3-032-08045-5_11
The microbiome–epigenome axis: Regulation of host genome function across development and disease
Abuhassan, Q., Atoom, A. M., Ganesan, S., Panigrahi, R., Kumar, V. R., Sharma, V., Chauhan, A. S., & Shodikulova, G. Z. (2026) · Cancer Treatment and Research Communications · doi:10.1016/j.ctarc.2026.101299
Epigenetics, bacterial metabolites and type 2 diabetes: a new view of gut-genome interactions
Taqi, A. F., Albuloushi, A., Saleh, A., Alqaderi, F., AlGharib, T., Al-Abdullah, L., Alzaïd, F., & Kandari, A. (2026) · Frontiers in Microbiology · doi:10.3389/fmicb.2026.1886562
Bonaventura, E. M. D., Botticelli, L., Pucci, M., Einaudi, G., Conte, E., Crestani, M., Luca, A. D., Palermo, F. A., Cifani, C., & Bonaventura, M. V. M. D. (2026) · Pharmacological Research · doi:10.1016/j.phrs.2026.109694
- Authors
- Ramos-Molina, B., Sánchez-Alcoholado, L., Cabrera-Mulero, A., Lopez-Dominguez, R., Carmona-Saez, P., Garcia-Fuentes, E., Moreno-Indias, I., & Tinahones, F. J.
- Affiliations
- Instituto de Salud Carlos III (ES)
- Venue
- Frontiers in Genetics
- Publisher
- Frontiers Media SA
- Published
- 2019-07-03
- Volume
- 10
- Pages
- 613-613
- ISSN
- 1664-8021 (ISSN-L)
- PMC
- PMC6616130
- OpenAlex
- W2953888736
- Cited by
- 64
- References
- 47
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 17 · 2023: 9 · 2022: 7 · 2021: 8 · 2020: 9 · 2019: 2
- FWCI
- 2.15
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Genetics (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- RISalud Institutional Health Repository of Andalucía (submittedVersion, cc-by)
- Institutional Repository of the University of Granada (University of Granada) (submittedVersion, cc-by)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Universidad Carlos III de Madrid
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- obesity, gut microbiota, DNA methylation, Firmicutes/Bacteroidetes ratio, adipose tissue, epigenetic regulation, HDAC7, IGF2BP2, differentially methylated genes
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