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Metabolic retroconversion of trimethylamine N-oxide and the gut microbiota

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Title: Metabolic retroconversion of trimethylamine N-oxide and the gut microbiota
Authors: Hoyles, L
Jiménez-Pranteda, MJ
Chilloux, J
Brial, F
Myridakis, A
Aranias, T
Magnan, C
Gibson, GR
Sanderson, JD
Nicholson, JK
Gauguier, D
McCartney, AL
Dumas, ME
Item Type: Journal Article
Abstract: Background: The dietary methylamines choline, carnitine, and phosphatidylcholine are used by the gut microbiota to produce a range of metabolites, including trimethylamine (TMA). However, little is known about the use of trimethylamine N-oxide (TMAO) by this consortium of microbes. Results: A feeding study using deuterated TMAO in C57BL6/J mice demonstrated microbial conversion of TMAO to TMA, with uptake of TMA into the bloodstream and its conversion to TMAO. Microbial activity necessary to convert TMAO to TMA was suppressed in antibiotic-treated mice, with deuterated TMAO being taken up directly into the bloodstream. In batch-culture fermentation systems inoculated with human faeces, growth of Enterobacteriaceae was stimulated in the presence of TMAO. Human-derived faecal and caecal bacteria (n = 66 isolates) were screened on solid and liquid media for their ability to use TMAO, with metabolites in spent media analysed by 1H-NMR. As with the in vitro fermentation experiments, TMAO stimulated the growth of Enterobacteriaceae; these bacteria produced most TMA from TMAO. Caecal/small intestinal isolates of Escherichia coli produced more TMA from TMAO than their faecal counterparts. Lactic acid bacteria produced increased amounts of lactate when grown in the presence of TMAO but did not produce large amounts of TMA. Clostridia (sensu stricto), bifidobacteria, and coriobacteria were significantly correlated with TMA production in the mixed fermentation system but did not produce notable quantities of TMA from TMAO in pure culture. Conclusions: Reduction of TMAO by the gut microbiota (predominantly Enterobacteriaceae) to TMA followed by host uptake of TMA into the bloodstream from the intestine and its conversion back to TMAO by host hepatic enzymes is an example of metabolic retroconversion. TMAO influences microbial metabolism depending on isolation source and taxon of gut bacterium. Correlation of metabolomic and abundance data from mixed microbiota fermentation systems did not give a true picture of which members of the gut microbiota were responsible for converting TMAO to TMA; only by supplementing the study with pure culture work and additional metabolomics was it possible to increase our understanding of TMAO bioconversions by the human gut microbiota.
Issue Date: 20-Apr-2018
Date of Acceptance: 12-Apr-2018
URI: http://hdl.handle.net/10044/1/59055
DOI: https://dx.doi.org/10.1186/s40168-018-0461-0
ISSN: 2049-2618
Publisher: BioMed Central
Journal / Book Title: Microbiome
Volume: 6
Copyright Statement: © The Author(s). 2018. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/ ) applies to the data made available in this article, unless otherwise stated.
Sponsor/Funder: Commission of the European Communities
Medical Research Council
Medical Research Council (MRC)
Funder's Grant Number: 305312
MRC Intermediate Research Fellow in Data Science
Keywords: Science & Technology
Life Sciences & Biomedicine
Co-metabolic axis
Gut-liver axis
Lactic acid bacteria
Gut–liver axis
Publication Status: Published
Article Number: 73
Appears in Collections:Department of Surgery and Cancer