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

Abstract

BackgroundIntestinal microbiota have been found to be linked to cardiovascular disease via conversion of the dietary compounds choline and carnitine to the atherogenic metabolite TMAO (trimethylamine‐N‐oxide). Specifically, a vegan diet was associated with decreased plasma TMAO levels and nearly absent TMAO production on carnitine challenge.Methods and ResultsWe performed a double‐blind randomized controlled pilot study in which 20 male metabolic syndrome patients were randomized to single lean vegan‐donor or autologous fecal microbiota transplantation. At baseline and 2 weeks thereafter, we determined the ability to produce TMAO from d6‐choline and d3‐carnitine (eg, labeled and unlabeled TMAO in plasma and 24‐hour urine after oral ingestion of 250 mg of both isotope‐labeled precursor nutrients), and fecal samples were collected for analysis of microbiota composition. 18F‐fluorodeoxyglucose positron emission tomography/computed tomography scans of the abdominal aorta, as well as ex vivo peripheral blood mononuclear cell cytokine production assays, were performed. At baseline, fecal microbiota composition differed significantly between vegans and metabolic syndrome patients. With vegan‐donor fecal microbiota transplantation, intestinal microbiota composition in metabolic syndrome patients, as monitored by global fecal microbial community structure, changed toward a vegan profile in some of the patients; however, no functional effects from vegan‐donor fecal microbiota transplantation were seen on TMAO production, abdominal aortic 18F‐fluorodeoxyglucose uptake, or ex vivo cytokine production from peripheral blood mononuclear cells.ConclusionsSingle lean vegan‐donor fecal microbiota transplantation in metabolic syndrome patients resulted in detectable changes in intestinal microbiota composition but failed to elicit changes in TMAO production capacity or parameters related to vascular inflammation.Clinical Trial Registration URL: http://www.trialregister.nl. Unique identifier: NTR 4338.

Gut microbiota: a promising target against cardiometabolic diseases

“…Vegetarians and vegans have lower endogenous TMAO levels than individuals following an omnivorous diet [96], due to their low carnitine intake or beneficial properties of their GM. However, FMT from lean-vegan donors to patients with metabolic syndrome did not change TMAO levels or markers of vascular inflammation [126]. In a recent study, mice with autoimmune myocarditis who received FMT from healthy mice had less myocardial injury due to reduced inflammatory infiltration [162].…”

“…A study in healthy controls did not show an effect of increased serum TMAO levels on cardiovascular mortality or hospitalization [125]; however, meta-analyses which included recent negative studies still confirmed the positive association between TMAO, CVD events, and mortality [113][114][115]. Likewise, FMT was not able to alter TMAO fluxes and vascular inflammation despite an effect on GM composition [126]. These processes can lead to atherosclerosis and as previously discussed, are influenced by the GM, which underlines the critical association between TMAO, GM, and CVD.…”

Gut microbiota and obesity: An opportunity to alter obesity through faecal microbiota transplant (FMT)

“…78 No changes in microbial diversity were observed in two of three FMT studies on patients with metabolic syndrome, although the gut microbiota composition was observed to be more similar to that of the donor. 55,78 The discrepancy observed in these studies compared with FMT trials on CDI that showed an increased microbial diversity in recipients may be a result of antibiotic use before FMT in the CDI trials or differing baseline gut microbiota composition between patients with CDI and metabolic syndrome. Albeit that there were positive changes in the recipient gut microbiota, there was no decrease in pro-atherosclerotic factors in the study by Smits et al, 55 suggesting that changes in gut microbiota may not necessarily result in functional change in metabolism.…”

“…Kootte et al also observed that FMT success was determined by decreased baseline microbial diversity . No changes in microbial diversity were observed in two of three FMT studies on patients with metabolic syndrome, although the gut microbiota composition was observed to be more similar to that of the donor . The discrepancy observed in these studies compared with FMT trials on CDI that showed an increased microbial diversity in recipients may be a result of antibiotic use before FMT in the CDI trials or differing baseline gut microbiota composition between patients with CDI and metabolic syndrome.…”

“…In more recent FMT studies in patients with metabolic syndrome, the gut microbiota of the recipient post-transplant resembled that of the donor. 55,78,107 Specifically, there was a noted increase in SCFAproducing bacteria, such as Roseburia intestinalis, 48 Bryantella formatexigens and Megamonas hypermegale, 55 which may have contributed to the improvements in insulin sensitivity in donor patients with metabolic syndrome. Donor-specific microbes, Roseburia hominis, Ruminococcus lactaris and A. muciniphila, were also able to successfully colonize the recipients, 103 with the latter being linked to improved host glucose tolerance.…”