Relationships between gut microbiota, plasma metabolites, and metabolic syndrome traits in the METSIM cohort

Abstract

BackgroundThe gut microbiome is a complex and metabolically active community that directly influences host phenotypes. In this study, we profile gut microbiota using 16S rRNA gene sequencing in 531 well-phenotyped Finnish men from the Metabolic Syndrome In Men (METSIM) study.ResultsWe investigate gut microbiota relationships with a variety of factors that have an impact on the development of metabolic and cardiovascular traits. We identify novel associations between gut microbiota and fasting serum levels of a number of metabolites, including fatty acids, amino acids, lipids, and glucose. In particular, we detect associations with fasting plasma trimethylamine N-oxide (TMAO) levels, a gut microbiota-dependent metabolite associated with coronary artery disease and stroke. We further investigate the gut microbiota composition and microbiota–metabolite relationships in subjects with different body mass index and individuals with normal or altered oral glucose tolerance. Finally, we perform microbiota co-occurrence network analysis, which shows that certain metabolites strongly correlate with microbial community structure and that some of these correlations are specific for the pre-diabetic state.ConclusionsOur study identifies novel relationships between the composition of the gut microbiota and circulating metabolites and provides a resource for future studies to understand host–gut microbiota relationships.Electronic supplementary materialThe online version of this article (doi:10.1186/s13059-017-1194-2) contains supplementary material, which is available to authorized users.

Composition of gut microbiota in obese and normal‐weight Mexican school‐age children and its association with metabolic traits

“…Gut microbiota has been recently found to be an important contributor to the increased serum BCAA and aromatic amino acid levels in obesity and its metabolic complications . In consistency with these studies, we observed significantly higher serum levels of BCAA (valine and leucine/isoleucine) and aromatic amino acids (phenylalanine and tyrosine) in obese children.…”

“…Interestingly, phenylalanine serum levels were found to have a negative and significant correlation with both B. plebeius and unclassified Christensenellaceae abundance. Although these correlations have not been previously reported, Christensenellaceae family abundance was negatively correlated with isoleucine and valine serum levels in Finnish adults .…”

“…Other studies have reported decreased gut microbial diversity in individuals with obesity and metabolic complications (6,7). Interestingly, abundance of certain bacterial species have recently been associated with high levels of aromatic and branched-chain amino acids (BCAA) (8,9), both linked to obesity and insulin resistance (10).…”

Effect of Vegan Fecal Microbiota Transplantation on Carnitine‐ and Choline‐Derived Trimethylamine‐N‐Oxide Production and Vascular Inflammation in Patients With Metabolic Syndrome

“…Interestingly, individuals on a vegan diet are known to have an altered intestinal microbiota composition, which might partly explain the diminished capacity to produce TMAO and the tendency toward decreased cardiovascular risk in vegans compared with omnivores . In contrast, omnivorous metabolic syndrome patients are known to have a 2‐fold increased cardiovascular risk as well as increased TMAO production . Plasma TMAO level in metabolic syndrome patients has been found to be an independent risk factor for CVD‐associated mortality, and TMAO production and associated atherosclerotic risk were transmittable by FMT in mice .…”

Gut microbiota‐derived metabolite trimethylamine N‐oxide (TMAO) potentially increases the risk of obesity in adults: An exploratory systematic review and dose‐response meta‐ analysis

“…Egg yolks, milk, dairy products, organ and muscle meats, and seafood such as mollusks, crustaceans, and fish are major dietary sources of TMAO and its precursors, although whether circulating TMAO is affected by dietary source needs to be further evaluated . There are numerous studies regarding the association between TMAO and biomarkers or risk factors of CVD, increased insulin resistance, impaired glucose metabolism, and metabolic syndrome . Possible suggested mechanisms about the association between TMAO and cardiovascular risk factors could be increased cholesterol accumulation in macrophages and in foam cells of artery walls or increased human platelet hyper‐responsiveness and potential of thrombosis in higher TMAO concentrations.…”