Circulating TMAO, the gut microbiome and cardiometabolic disease risk: an exploration in key precursor disorders

• Published in: Diabetology and metabolic syndrome Vol. 16; no. 1; pp. 1 - 16
• Main Authors: Naghipour, Saba, Cox, Amanda J, Fisher, Joshua J, Plan, Manuel, Stark, Terra, West, Nic, Peart, Jason N, Headrick, John P, Du Toit, Eugene F
• Format: Journal Article
• Language: English
• Published: London BioMed Central Ltd 17.06.2024; BioMed Central; BMC
• Subjects: Analysis; Australia; Bacteria; Biological markers; Biomarkers; Body mass index; Cardiometabolic disease; Cardiovascular diseases; Care and treatment; Carnitine; Cholesterol; Chronic illnesses; Composition; Development and progression; Diabetes; Diagnosis; Diet; Diseases; Gut microbiota; Health aspects; Heart failure; High density lipoprotein; Hypertension; Instrument industry; Intestinal microflora; Japan; Kidney diseases; Metabolic diseases; Metabolic disorders; Metabolic syndrome; Metabolism; Metabolites; Microbiomes; Microbiota (Symbiotic organisms); Obesity; Overweight; Pathology; Phenotypes; Phenotypic variations; Plasma; Risk factors; Seafood; Taxonomy; Triglycerides; Trimethylamine; Trimethylamine-N-oxide; Type 2 diabetes; Womens health; Australia; Japan; United States > US; Melbourne Victoria Australia
• ISSN: 1758-5996; 1758-5996
• DOI: 10.1186/s13098-024-01368-y

Background Elevations in the gut metabolite trimethylamine-N-oxide (TMAO) have been linked to cardiovascular and metabolic diseases. Whether elevated TMAO levels reflect early mechanistic involvement or a sequela of evolving disease awaits elucidation. The purpose of this study was to further explore these potential associations. Methods We investigated relationships between circulating levels of TMAO and its pre-cursor substrates, dietary factors, gut microbiome profiles and disease risk in individuals with a Healthy BMI (18.5 < BMI < 25, n = 41) or key precursor states for cardiometabolic disease: Overweight (25 < BMI < 30 kg/m.sup.2, n = 33), Obese (BMI > 30, n = 27) and Metabolic Syndrome (MetS; [greater than or equal to] 3 ATPIII report criteria, n = 39). Results Unexpectedly, plasma [TMAO] did not vary substantially between groups (means of 3-4 [micro]M; p > 0.05), although carnitine was elevated in participants with MetS. Gut microbial diversity and Firmicutes were also significantly reduced in the MetS group (p < 0.05). Exploratory analysis across diverse parameters reveals significant correlations between circulating [TMAO] and seafood intake (p = 0.007), gut microbial diversity (p = 0.017-0.048), and plasma [trimethylamine] (TMA; p = 0.001). No associations were evident with anthropometric parameters or cardiometabolic disease risk. Most variance in [TMAO] within and between groups remained unexplained. Conclusions Data indicate that circulating [TMAO] may be significantly linked to seafood intake, levels of TMA substrate and gut microbial diversity across healthy and early disease phenotypes. However, mean concentrations remain < 5 [micro]M, with little evidence of links between TMAO and cardiometabolic disease risk. These observations suggest circulating TMAO may not participate mechanistically in cardiometabolic disease development, with later elevations likely a detrimental sequela of extant disease. Keywords: Cardiometabolic disease, Diet, Gut microbiota, Metabolic syndrome, Obesity, Trimethylamine-N-oxide, Diabetes