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ToolsDay-Walsh, Priscilla, Shehata, Emad, Saha, Shikha, Savva, George M., Nemeckova, Barbora, Speranza, Jasmine, Kellingray, Lee, Narbad, Arjan and Kroon, Paul A. (2021) The use of an in-vitro batch fermentation (human colon) model for investigating mechanisms of TMA production from choline, L-carnitine and related precursors by the human gut microbiota. European Journal of Nutrition, 60 (7). pp. 3987-3999. ISSN 1436-6207
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Abstract
Purpose: Plasma trimethylamine-N-oxide (TMAO) levels have been shown to correlate with increased risk of metabolic diseases including cardiovascular diseases. TMAO exposure predominantly occurs as a consequence of gut microbiota-dependent trimethylamine (TMA) production from dietary substrates including choline, carnitine and betaine, which is then converted to TMAO in the liver. Reducing microbial TMA production is likely to be the most effective and sustainable approach to overcoming TMAO burden in humans. Current models for studying microbial TMA production have numerous weaknesses including the cost and length of human studies, differences in TMA(O) metabolism in animal models and the risk of failing to replicate multi-enzyme/multi-strain pathways when using isolated bacterial strains. The purpose of this research was to investigate TMA production from dietary precursors in an in-vitro model of the human colon. Methods: TMA production from choline, l-carnitine, betaine and γ-butyrobetaine was studied over 24–48 h using an in-vitro human colon model with metabolite quantification performed using LC–MS. Results: Choline was metabolised via the direct choline TMA-lyase route but not the indirect choline–betaine-TMA route, conversion of l-carnitine to TMA was slower than that of choline and involves the formation of the intermediate γ-BB, whereas the Rieske-type monooxygenase/reductase pathway for l-carnitine metabolism to TMA was negligible. The rate of TMA production from precursors was choline > carnitine > betaine > γ-BB. 3,3-Dimethyl-1-butanol (DMB) had no effect on the conversion of choline to TMA. Conclusion: The metabolic routes for microbial TMA production in the colon model are consistent with observations from human studies. Thus, this model is suitable for studying gut microbiota metabolism of TMA and for screening potential therapeutic targets that aim to attenuate TMA production by the gut microbiota. Trial registration number: NCT02653001 (http://www.clinicaltrials.gov), registered 12 Jan 2016.
| Item Type: | Article |
|---|---|
| Additional Information: | Funding information: This research was funded by the Biotechnology and Biological Sciences Research Council (UK) through the Institute Strategic Programme Grants ‘Food and Health’ (Grant No. BB/J004545/1) and ‘Food Innovation and Health’ (Grant No. BB/R012512/1 and its constituent projects BBS/E/F/000PR10343, BBS/E/F/000PR10346 and BBS/E/F/000PR10347) to the Quadram Institute Bioscience. Emad Shehata was funded by the Newton-Mosharafa Scholarship Fund from the Egyptian Ministry of Higher Education (Cultural Affairs and Mission sector), the British Council and the British Embassy in Egypt. GS is supported by the BBSRC Core Capability Grant BB/CCG1860/1. |
| Uncontrolled Keywords: | betaine,cardiovascular disease,carnitine,fish odour syndrome,human gut microbiota,lecithin,metabolic disease,phosphatidylcholine,tmao,γ-butyrobetaine,medicine (miscellaneous),nutrition and dietetics ,/dk/atira/pure/subjectarea/asjc/2700/2701 |
| Faculty \ School: | Faculty of Medicine and Health Sciences > School of Health Sciences Faculty of Science > School of Biological Sciences |
| Related URLs: | |
| Depositing User: | LivePure Connector |
| Date Deposited: | 19 Feb 2025 09:30 |
| Last Modified: | 21 Feb 2025 09:30 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/98547 |
| DOI: | 10.1007/s00394-021-02572-6 |
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