Effects of pomegranate polyphenols on the gut microbiota-dependent production of proatherogenic trimethylamine from L-carnitine

Haarhuis, Julia Eva (2025) Effects of pomegranate polyphenols on the gut microbiota-dependent production of proatherogenic trimethylamine from L-carnitine. Doctoral thesis, University of East Anglia.

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Abstract

Background: Cardiovascular disease (CVD) is the leading cause of mortality worldwide, with circulating trimethylamine N-oxide (TMAO) levels receiving increasing attention as a potential risk factor. TMAO is formed from trimethylamine (TMA), a microbial metabolite of dietary precursors including L-carnitine. Dietary polyphenols have been proposed to reduce TMAO production, but mechanistic evidence and pharmacokinetic studies investigating the effect of polyphenols on TMAO production are limited.

Objectives: The research described here aimed to determine whether a polyphenol-rich pomegranate extract can reduce microbial TMA production from L-carnitine and lower circulating TMAO concentrations, and to elucidate several possible underlying mechanisms involved.

Approaches: In vitro colon models were used to test the effects of a pomegranate extract on microbial L-carnitine metabolism. A two-phase, double-blind, randomised, placebo-controlled, crossover intervention study in 16 healthy adults investigated the effect of a pomegranate extract on plasma TMAO levels. Mechanistic experiments involved colony forming unit (CFU) counting, quantitative polymerase chain reaction (qPCR) assays, and a metagenomic analysis.

Results: The extract and its main polyphenol, punicalagin, substantially suppressed TMA production. Mechanistic experiments suggested that the effects were not due to general or selective antibacterial activity. The intervention study showed that a single 1.6 g dose of the pomegranate extract did not significantly reduce plasma TMAO production from an oral L-carnitine challenge in the overall study population. However, in male and premenopausal female participants, the extract modestly reduced TMAO production.

Conclusion: Together, these findings provide evidence that a pomegranate extract and punicalagin inhibit microbial TMA formation and may attenuate TMAO responses in specific population subgroups. These results support the broader concept that polyphenol-rich foods could represent a dietary strategy for reducing TMAO exposure and potentially CVD risk. Further work is required to clarify underlying mechanisms and determine the effects among different population groups through larger, longer-term intervention studies.

Item Type:	Thesis (Doctoral)
Faculty \ School:	Faculty of Science > School of Biological Sciences
Depositing User:	Chris White
Date Deposited:	22 Dec 2025 10:47
Last Modified:	22 Dec 2025 10:47
URI:	https://ueaeprints.uea.ac.uk/id/eprint/101470
DOI:

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