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Microbiome. 2018 Apr 20;6(1):73. doi: 10.1186/s40168-018-0461-0.

Metabolic retroconversion of trimethylamine N-oxide and the gut microbiota.

Author information

1
Integrative Systems Medicine and Digestive Disease, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Exhibition Road, London, SW7 2AZ, UK.
2
Food Microbial Sciences Unit, Department of Food and Nutritional Sciences, School of Chemistry, Food and Pharmacy, Faculty of Life Sciences, The University of Reading, Whiteknights Campus, Reading, RG6 6UR, UK.
3
Sorbonne Universities, University Pierre & Marie Curie, University Paris Descartes, Sorbonne Paris Cité, INSERM UMR_S 1138, Cordeliers Research Centre, Paris, France.
4
Sorbonne Paris Cité, Université Denis Diderot, Unité de Biologie Fonctionnelle et Adaptative, CNRS UMR 8251, 75205, Paris, France.
5
Department of Gastroenterology, Guy's and St Thomas' NHS Foundation Trust and King's College London, London, UK.
6
Food Microbial Sciences Unit, Department of Food and Nutritional Sciences, School of Chemistry, Food and Pharmacy, Faculty of Life Sciences, The University of Reading, Whiteknights Campus, Reading, RG6 6UR, UK. a.l.mccartney@reading.ac.uk.
7
Integrative Systems Medicine and Digestive Disease, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Exhibition Road, London, SW7 2AZ, UK. m.dumas@imperial.ac.uk.

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.

KEYWORDS:

Co-metabolic axis; Enterobacteriaceae; Gut–liver axis; Lactic acid bacteria; Metabolomics

PMID:
29678198
PMCID:
PMC5909246
DOI:
10.1186/s40168-018-0461-0
[Indexed for MEDLINE]
Free PMC Article

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