ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2019
Two-carbon folate cycle of commensal Lactobacillus reuteri 6475 gives rise to immunomodulatory ethionine, a source for histone ethylation.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 33 citations in OpenAlex.
- Methanosarcina acetivorans requires methanol:coenzyme M methyltransferases for ethane formation from ethanol.Antonie van Leeuwenhoek · 2025Article
- Chemical interplay between gut microbiota and epigenetics: Implications in circadian biology.Cell chemical biology · 2025Review
- Postbiotics Implication in the Microbiota-Host Intestinal Epithelial Cells Mutualism.Probiotics and antimicrobial proteins · 2024Review
- The potential of short-chain fatty acid epigenetic regulation in chronic low-grade inflammation and obesity.Frontiers in immunology · 2024Review
- Multi-omics analysis of fecal samples in colorectal cancer Egyptians patients: a pilot study.BMC microbiology · 2023Article
- The possible role of gut microbiota dysbiosis in the pathophysiology of delirium in older persons.Microbiome research reports · 2023Review
- Microbiome and Metabolomics in Liver Cancer: Scientific Technology.International journal of molecular sciences · 2022Review
- Airway microbiome-immune crosstalk in chronic obstructive pulmonary disease.Frontiers in immunology · 2022Review
- Next-Generation Probiotic Therapy to Protect the Intestines From Injury.Frontiers in cellular and infection microbiology · 2022Review
- Metabolic folate profiling as a function of time during cultivation suggests potential C2-metabolism inFrontiers in nutrition · 2022Article
- The probiotic and immunomodulation effects ofFrontiers in cellular and infection microbiology · 2022Article
- Review
- Review
- Gut microbial metabolites as multi-kingdom intermediates.Nature reviews. Microbiology · 2021Review
- Emerging Evidence on the Effects of Dietary Factors on the Gut Microbiome in Colorectal Cancer.Frontiers in nutrition · 2021Review
- "Osteomicrobiology": The Nexus Between Bone and Bugs.Frontiers in microbiology · 2021Review
- Epigenome-metabolome-microbiome axis in health and IBD.Current opinion in microbiology · 2020Review
- Gut Microbiota as Important Mediator Between Diet and DNA Methylation and Histone Modifications in the Host.Nutrients · 2020Review
- Complex Responses to Hydrogen Peroxide and Hypochlorous Acid by the Probiotic Bacterium Lactobacillus reuteri.mSystems · 2019Article
- Microbial Metabolic Capacity for Intestinal Folate Production and Modulation of Host Folate Receptors.Frontiers in microbiology · 2019Article
Corrections and comments
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Authors and funding
7 authors at 5 institutions in 1 country.
Funding
Abstract
Colonization of the gut by certain probiotic Lactobacillus reuteri strains has been associated with reduced risk of inflammatory diseases and colorectal cancer. Previous studies pointed to a functional link between immunomodulation, histamine production, and folate metabolism, the central 1-carbon pathway for the transfer of methyl groups. Using mass spectrometry and NMR spectroscopy, we analyzed folate metabolites of L. reuteri strain 6475 and discovered that the bacterium produces a 2-carbon-transporting folate in the form of 5,10-ethenyl-tetrahydrofolyl polyglutamate. Isotopic labeling permitted us to trace the source of the 2-carbon unit back to acetate of the culture medium. We show that the 2C folate cycle of L. reuteri is capable of transferring 2 carbon atoms to homocysteine to generate the unconventional amino acid ethionine, a known immunomodulator. When we treated monocytic THP-1 cells with ethionine, their transcription of TNF-α was inhibited and cell proliferation reduced. Mass spectrometry of THP-1 histones revealed incorporation of ethionine instead of methionine into proteins, a reduction of histone-methylation, and ethylation of histone lysine residues. Our findings suggest that the microbiome can expose the host to ethionine through a novel 2-carbon transporting variant of the folate cycle and modify human chromatin via ethylation.-Röth, D., Chiang, A. J., Hu, W., Gugiu, G. B., Morra, C. N., Versalovic, J., Kalkum, M. The two-carbon folate cycle of commensal Lactobacillus reuteri 6475 gives rise to immunomodulatory ethionine, a source for histone ethylation.
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Registered trials
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