Plasma TMAO Concentrations and Gut Microbiota Composition in Subjects with and Without Metabolic Syndrome: Results from Pilot Study

<b>Background/Objectives</b>: Trimethylamine N-oxide (TMAO) is a gut microbiota-dependent metabolite considered as a risk metabolite for various non-communicable diseases. This study aims to identify differences in the gut microbiota composition and concentrations of TMAO and related met...

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Main Authors: Mohammed E. Hefni, Cornelia M. Witthöft, Patrik Hellström, Ingegerd Johansson, Anders Esberg
Format: Article
Language:English
Published: MDPI AG 2025-05-01
Series:Metabolites
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Online Access:https://www.mdpi.com/2218-1989/15/6/364
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author Mohammed E. Hefni
Cornelia M. Witthöft
Patrik Hellström
Ingegerd Johansson
Anders Esberg
author_facet Mohammed E. Hefni
Cornelia M. Witthöft
Patrik Hellström
Ingegerd Johansson
Anders Esberg
author_sort Mohammed E. Hefni
collection DOAJ
description <b>Background/Objectives</b>: Trimethylamine N-oxide (TMAO) is a gut microbiota-dependent metabolite considered as a risk metabolite for various non-communicable diseases. This study aims to identify differences in the gut microbiota composition and concentrations of TMAO and related metabolites in subjects with and without metabolic syndrome (MetS). <b>Methods</b>: Plasma samples were collected following an overnight fast on two occasions from subjects with (n = 12) and without (n = 21) MetS. Feces samples were collected on the day before the first blood sampling. The gut microbiota was profiled using 16S rRNA full-gene amplification sequencing. TMAO and related methylamines were quantified using UPLC-MSMS. The fasted plasma glucose, plasma lipid profile, and HbA1c were determined, and blood pressure, circumference, height, and weight were measured. <b>Results</b>: A divergent gut microbiota composition was observed in feces samples from both groups. In contrast to subjects without MetS, subjects with MetS had a reduced microbial diversity, with lower <i>Blautia glucerasea</i> and higher <i>Ruminococcus torques</i>—a pattern associated with (increased) inflammation. Trimethylamine (TMA)-producing bacteria were low in abundance across both groups. While plasma TMAO and related methylamines displayed no significant differences between both groups, L-carnitine was elevated (<i>p</i> = 0.0191) in subjects with MetS. A strong positive correlation was detected between TMAO and TMA (<i>r</i> = 0.439, <i>p</i> = 0.003), with a tendency to correlate with carnitine (<i>r</i> = 0.212, <i>p</i> = 0.087). <b>Conclusions</b>: Subjects with MetS were characterized by gut microbiota favoring inflammation-associated species but not TMA producers. This suggests that TMAO may not play a role in MetS subjects without overt comorbidities, e.g., CVD or T2D. The influence of the gut microbiota on early MetS is likely mediated through inflammatory mechanisms driven by specific bacterial shifts rather than TMAO production.
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spelling doaj-art-cad658fb94334c94808b6c2bc2fd238a2025-08-20T03:27:40ZengMDPI AGMetabolites2218-19892025-05-0115636410.3390/metabo15060364Plasma TMAO Concentrations and Gut Microbiota Composition in Subjects with and Without Metabolic Syndrome: Results from Pilot StudyMohammed E. Hefni0Cornelia M. Witthöft1Patrik Hellström2Ingegerd Johansson3Anders Esberg4Department of Chemistry and Biomedical Sciences, Linnaeus University, 392 31 Kalmar, SwedenDepartment of Chemistry and Biomedical Sciences, Linnaeus University, 392 31 Kalmar, SwedenDepartment of Health and Caring Sciences, Linnaeus University, 392 31 Kalmar, SwedenDepartment of Odontology, Umeå University, 901 87 Umeå, SwedenDepartment of Odontology, Umeå University, 901 87 Umeå, Sweden<b>Background/Objectives</b>: Trimethylamine N-oxide (TMAO) is a gut microbiota-dependent metabolite considered as a risk metabolite for various non-communicable diseases. This study aims to identify differences in the gut microbiota composition and concentrations of TMAO and related metabolites in subjects with and without metabolic syndrome (MetS). <b>Methods</b>: Plasma samples were collected following an overnight fast on two occasions from subjects with (n = 12) and without (n = 21) MetS. Feces samples were collected on the day before the first blood sampling. The gut microbiota was profiled using 16S rRNA full-gene amplification sequencing. TMAO and related methylamines were quantified using UPLC-MSMS. The fasted plasma glucose, plasma lipid profile, and HbA1c were determined, and blood pressure, circumference, height, and weight were measured. <b>Results</b>: A divergent gut microbiota composition was observed in feces samples from both groups. In contrast to subjects without MetS, subjects with MetS had a reduced microbial diversity, with lower <i>Blautia glucerasea</i> and higher <i>Ruminococcus torques</i>—a pattern associated with (increased) inflammation. Trimethylamine (TMA)-producing bacteria were low in abundance across both groups. While plasma TMAO and related methylamines displayed no significant differences between both groups, L-carnitine was elevated (<i>p</i> = 0.0191) in subjects with MetS. A strong positive correlation was detected between TMAO and TMA (<i>r</i> = 0.439, <i>p</i> = 0.003), with a tendency to correlate with carnitine (<i>r</i> = 0.212, <i>p</i> = 0.087). <b>Conclusions</b>: Subjects with MetS were characterized by gut microbiota favoring inflammation-associated species but not TMA producers. This suggests that TMAO may not play a role in MetS subjects without overt comorbidities, e.g., CVD or T2D. The influence of the gut microbiota on early MetS is likely mediated through inflammatory mechanisms driven by specific bacterial shifts rather than TMAO production.https://www.mdpi.com/2218-1989/15/6/364gut microbiotametabolic syndromeTMAOTMAcholinecarnitine
spellingShingle Mohammed E. Hefni
Cornelia M. Witthöft
Patrik Hellström
Ingegerd Johansson
Anders Esberg
Plasma TMAO Concentrations and Gut Microbiota Composition in Subjects with and Without Metabolic Syndrome: Results from Pilot Study
Metabolites
gut microbiota
metabolic syndrome
TMAO
TMA
choline
carnitine
title Plasma TMAO Concentrations and Gut Microbiota Composition in Subjects with and Without Metabolic Syndrome: Results from Pilot Study
title_full Plasma TMAO Concentrations and Gut Microbiota Composition in Subjects with and Without Metabolic Syndrome: Results from Pilot Study
title_fullStr Plasma TMAO Concentrations and Gut Microbiota Composition in Subjects with and Without Metabolic Syndrome: Results from Pilot Study
title_full_unstemmed Plasma TMAO Concentrations and Gut Microbiota Composition in Subjects with and Without Metabolic Syndrome: Results from Pilot Study
title_short Plasma TMAO Concentrations and Gut Microbiota Composition in Subjects with and Without Metabolic Syndrome: Results from Pilot Study
title_sort plasma tmao concentrations and gut microbiota composition in subjects with and without metabolic syndrome results from pilot study
topic gut microbiota
metabolic syndrome
TMAO
TMA
choline
carnitine
url https://www.mdpi.com/2218-1989/15/6/364
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