A red wine intervention does not modify plasma trimethylamine N-oxide but is associated with broad shifts in the plasma metabolome and gut microbiota composition

Abstract

Background Gut microbiota profiles are closely related to cardiovascular diseases through mechanisms that include the reported deleterious effects of metabolites, such as trimethylamine N-oxide (TMAO), which have been studied as diagnostic and therapeutic targets. Moderate red wine (RW) consumption is reportedly cardioprotective, possibly by affecting the gut microbiota. Objective To investigate the effects of RW consumption on the gut microbiota, plasma TMAO, and the plasma metabolome in males with documented coronary artery disease (CAD) using a multiomics assessment in a crossover trial. Methods We conducted a randomized, crossover, controlled trial involving 42 males (average age, 60 years) with documented CAD comparing 3-week RW consumption (250 mL/day, 5 days/week) with an equal period of alcohol abstention, both preceded by a 2-week washout period. The gut microbiota was analyzed via 16S rRNA high-throughput sequencing. Plasma TMAO was evaluated by liquid chromatography coupled with mass spectrometry (LC-MS/MS). The plasma metabolome of 20 randomly selected participants was evaluated by ultra-high-performance LC-MS/MS. The effect of RW consumption was assessed by individual comparisons using paired tests during the abstention and RW periods. Results Plasma TMAO did not differ between RW intervention and alcohol abstention, and TMAO levels showed low intraindividual concordance over time, with an intraclass correlation coefficient of 0.049 during the control period. After RW consumption, there was significant remodeling of the gut microbiota, with a difference in beta diversity and predominance of Parasutterella, Ruminococcaceae, several Bacteroides species and Prevotella. Plasma metabolomic analysis revealed significant changes in metabolites after RW consumption, consistent with improved redox homeostasis. Conclusions Modulation of the gut microbiota may contribute to the putative cardiovascular benefits of moderate RW consumption. The low intraindividual concordance of TMAO presents challenges regarding its role as a cardiovascular risk biomarker at the individual level. This study was registered at clinical trials.gov, NCT03232099.

Health Effects of Red Wine Consumption: A Narrative Review of an Issue That Still Deserves Debate

“…Similar results in terms of increased faecal microbial diversity, have been obtained both in healthy individuals [81,99] and in patients with metabolic alterations associated with obesity [83]. Plasma trimethylamine N-oxide (TMAO) did not differ between people receiving the RW intervention and ET abstention [99].…”

“…Another study demonstrated that RW consumption induced a significant increase in amounts of Bifidobacterium and Prevotella with a negative correlation with lipopolysaccharide (LPS) plasma concentration [73]. Similar results in terms of increased faecal microbial diversity, have been obtained both in healthy individuals [81,99] and in patients with metabolic alterations associated with obesity [83]. Plasma trimethylamine N-oxide (TMAO) did not differ between people receiving the RW intervention and ET abstention [99].…”

“…Studies have shown that plant-based diets, such as the MD, vegetarian, and vegan diets, can effectively improve TMAO levels, while animal-based diets appear to have the opposite effect [142,143]. The only recent RCT included in the review [99] that evaluated TMAO concluded that TMAO concentrations were unrelated to RW intake. The addition of RW to a plant-based diet would offer no further benefit in reducing blood and urine values of TMAO, as suggested in a previous paper [144].…”

Human gut microbiome: Therapeutic opportunities for metabolic syndrome—Hype or hope?

“…Red wine consumption was significantly associated with an increase in the relative abundance of Bacteroides , Ruminococcaceae , Roseburia and Prevotella . Interestingly, Parasutterella was the most prominent genus for differentiating the gut microbiota of the participants who consumed red wine 52 . A previous study showed that Parasutterella supports interspecies metabolic interactions within the healthy gut ecosystem 53 .…”

“…Interestingly, Parasutterella was the most prominent genus for differentiating the gut microbiota of the participants who consumed red wine. 52 A previous study showed that Parasutterella supports interspecies metabolic interactions within the healthy gut ecosystem. 53 A recent review investigated the potential benefits of theaflavins, found in red wine, on metabolic syndrome, with a focus on the gut microbiome.…”