Modulating microbial production of trimethylamine from choline with probiotics and polyphenols

Peck, Barbora (2024) Modulating microbial production of trimethylamine from choline with probiotics and polyphenols. Doctoral thesis, University of East Anglia.

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Abstract

Background: The gut microbiota is essential in metabolising dietary components like choline and carnitine, producing trimethylamine (TMA) in the colon which is then converted into trimethylamine N-oxide (TMAO) in the liver. TMAO has been linked to cardiovascular disease (CVD) risk and development of atherosclerosis. Despite debates on the use of TMAO as a disease marker, due to its prognostic properties in CVD pathogenesis it is paramount to identify effective treatments for at-risk individuals.

Objective: This thesis aimed to investigate the capacity of human gut microbiota to produce TMA and develop strategies for modulating microbial TMA production from choline using probiotics and polyphenols.

Approaches: In-vivo TMAO levels were assessed in plasma and urine and their relationship with the in-vitro capacity to produce TMA from choline was investigated for correlations with the structure and function of the gut microbiota using shotgun metagenomics approach. A mixed-strain probiotic supplement and its components were tested using in-vitro colon models for their effect on TMA production in faecal samples and TMA-producing strains, while polyphenols were screened for inhibitory effects on TMA production from choline.

Results: In-vivo TMAO status did not correlate with TMA production capacity measured in-vitro, but significant correlations were found between these variables and gut microbiota composition and function. Mixed probiotic supplement minimally affected TMA production, yet its individual strains showed promise in faecal matrices. Polyphenols, particularly more complex structures, demonstrated inhibitory effects on choline metabolism though different mechanisms of action.

Conclusion: This work deepened our understanding of the role of the gut microbiota in TMA production and its relationship with in-vivo TMAO status. By investigating the role of probiotics and polyphenols in reducing TMA production from choline, targeted strategies for mitigating risks associated with elevated TMAO levels can be established in the future. These insights may guide the development of dietary interventions to modulate the gut microbiota-mediated and reduce elevated TMAO levels.

Item Type:	Thesis (Doctoral)
Faculty \ School:	Faculty of Science > School of Biological Sciences
Depositing User:	Zoe White
Date Deposited:	18 Feb 2025 16:05
Last Modified:	18 Feb 2025 16:05
URI:	https://ueaeprints.uea.ac.uk/id/eprint/98544
DOI:

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