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Metabolic, Epigenetic, and Transgenerational Effects of Gut Bacterial Choline Consumption
Open accessAbstract
Choline is an essential nutrient and methyl donor required for epigenetic regulation. Here, we assessed the impact of gut microbial choline metabolism on bacterial fitness and host biology by engineering a microbial community that lacks a single choline-utilizing enzyme. Our results indicate that choline-utilizing bacteria compete with the host for this nutrient, significantly impacting plasma and hepatic levels of methyl-donor metabolites and recapitulating biochemical signatures of choline deficiency. Mice harboring high levels of choline-consuming bacteria showed increased susceptibility to metabolic disease in the context of a high-fat diet. Furthermore, bacterially induced reduction of methyl-donor availability influenced global DNA methylation patterns in both adult mice and their offspring and engendered behavioral alterations. Our results reveal an underappreciated effect of bacterial choline metabolism on host metabolism, epigenetics, and behavior. This work suggests that interpersonal differences in microbial metabolism should be considered when determining optimal nutrient intake requirements.
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“The presence of the microbial cutC/D genes in human microbiota are associated with the ability to generate TMA from choline120, and with subsequent TMAO accumulation121.”
From Gut microbiota and cardiovascular disease. (2020) · cites this paper as [121]
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“Microbial metabolites including folate, butyrate and acetate are cofactors and allosteric regulators of epigenetic processes such as DNA methylation, histone acetylation and RNA interference190–192.”
From The gut microbiota and the brain–gut–kidney axis in hypertension and chronic kidney disease (2018) · cites this paper as [190]
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“Together, the available data suggest that epigenetic changes mediated by the gut microbiota are involved in the pathogenesis of dysbiosis-associated hypertension and CKD.”
From The gut microbiota and the brain–gut–kidney axis in hypertension and chronic kidney disease (2018) · cites this paper as [190]
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Self-citationLucas, L. N., Mallikarjun, J., Cattaneo, L. E., Gangwar, B., Zhang, Q., Clay, A. P., Kerby, R. L., Stevenson, D. M., Blackwell, H. E., Rey, F. E., et al. (2026) · Nature Communications · doi:10.1038/s41467-026-68556-4 · Cited by 28
Self-citation
Metadata
- Authors
- Romano, K. A., Martinez-del Campo, A., Kasahara, K., Chittim, C. L., Vivas, E. I., Amador-Noguez, D., Balskus, E. P., & Rey, F. E.
- Affiliations
- University of Wisconsin–Madison (US)
- Harvard University (US)
- Corresponding author
- Balskus, Emily P.
- Rey, Federico E.
- Venue
- Cell Host & Microbe
- Publisher
- Elsevier BV
- Published
- 2017-09
- Volume
- 22
- Issue
- 3
- Pages
- 279-290.e7
- ISSN
- 1931-3128 (ISSN-L)
- PMC
- PMC5599363
- OpenAlex
- W2750083495
- Cited by
- 224
- References
- 71
- Citations by year
- 2026: 24 · 2025: 34 · 2024: 30 · 2023: 14 · 2022: 24 · 2021: 30 · 2020: 21 · 2019: 21 · 2018: 23 · 2017: 3
- FWCI
- 7.67
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Host & Microbe (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NIH (DK108259)
- Smith Family Award for Biomedical Research
- Packard Fellowship for Science and Engineering (2013-39267)
- Blavatnik Biomedical Accelerator Award
- National Institute of Food and Agriculture, U.S. Department of Agriculture (WIS01910)
- Hatch (WIS01901)
- 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
- Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Nutrition and Physiology
- Keywords
- choline metabolism, gut microbiota, methyl donors, DNA methylation, epigenetics, transgenerational effects, choline deficiency, high-fat diet, metabolic disorders, host behavior, microbial community engineering
- MeSH terms
- Gastrointestinal Microbiome, Animals, Bacteria, Choline, Female, Humans, Intestinal Mucosa, Intestines, Male, Metabolic Diseases, Mice, Inbred C57BL, DNA Methylation, Epigenesis, Genetic
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