Evidence suggesting the role of the gut microbiota in maintaining host health has become mainstream. Multiple strategies to modulate the gut microbiome composition have emerged such as Probiotics, Prebiotics, Synbiotics or Faecal Microbiota Transplant.

Among the list of prebiotic fibers, plant polyphenols with an estimated 90–95% that are not absorbed in the small intestine but reach the colon, where they undergo extensive biotransformation by the gut microbiota. Dr. Robert E. Steinert, main author of this publication, explained that natural products rich in polyphenols have been hypothesized to lower plasma trimethylamine-n-oxide (TMAO), an emerging biomarker known for its proatherogenic effects by beneficially modulating the intestinal microbiota.

Dr. Marcus Claesson added: Previously thought to be a waste product of choline metabolism with no physiological function, trimethylamine-N-oxide (TMAO), a chemical metabolite derived from diet and metabolized by the gut microbiota, is now supported by growing evidence for its involvement in inflammation, cardiovascular disease, and obesity. A high level of TMAO may increase the risk of clot-related events like heart attack and stroke, according to research (2). Thus, a changed gut microbiota and increased intestinal permeability may be the causes of chronic inflammation, which worsens cardiac function (3).

TMA is a microbial metabolite produced by the gut microbiome from dietary phosphatidylcholine and L-carnitine, commonly found in red meat, cheese and eggs. When absorbed by the intestinal epithelium and transported to the liver, TMA is transformed into TMAO. TMAO is known for its proinflammatory and proatherogenic activities. Higher levels of TMAO have been linked to major adverse cardiovascular events.

Evidence suggesting the role of the gut microbiota in maintaining host health has become mainstream. Multiple strategies to modulate the gut microbiome composition have emerged such as Probiotics, Prebiotics, Synbiotics or Faecal Microbiota Transplant.

Among the list of prebiotic fibers, plant polyphenols with an estimated 90–95% that are not absorbed in the small intestine but reach the colon, where they undergo extensive biotransformation by the gut microbiota. Dr. Robert E. Steinert, main author of this publication, explained that natural products rich in polyphenols have been hypothesized to lower plasma trimethylamine-n-oxide (TMAO), an emerging biomarker known for its proatherogenic effects by beneficially modulating the intestinal microbiota.

Dr. Marcus Claesson added: Previously thought to be a waste product of choline metabolism with no physiological function, trimethylamine-N-oxide (TMAO), a chemical metabolite derived from diet and metabolized by the gut microbiota, is now supported by growing evidence for its involvement in inflammation, cardiovascular disease, and obesity. A high level of TMAO may increase the risk of clot-related events like heart attack and stroke, according to research (2). Thus, a changed gut microbiota and increased intestinal permeability may be the causes of chronic inflammation, which worsens cardiac function (3).

TMA is a microbial metabolite produced by the gut microbiome from dietary phosphatidylcholine and L-carnitine, commonly found in red meat, cheese and eggs. When absorbed by the intestinal epithelium and transported to the liver, TMA is transformed into TMAO. TMAO is known for its proinflammatory and proatherogenic activities. Higher levels of TMAO have been linked to major adverse cardiovascular events.

Fruitflow^® significantly decreased fasting blood and urine TMAO when compared to baseline as well as plasma LPS, a marker of intestinal permeability and low-grade inflammation. Moreover, when compared to the placebo group, this was also significantly different for urine TMAO. Dr. Steinert further explained the mechanism of action studied in this trial: Indeed, Fruitflow^® seems to modulate the gut microbiota in a way that resulted in a lowering of urine and plasma TMAO. Moreover, we found that Fruitflow^® reduced plasma lipopolysaccharides (LPS), a gut microbiota-derived factor that has been suggested to drive onset and progression of chronic inflammation-related diseases such as obesity, type 2 diabetes or non-alcoholic fatty liver disease (NAFLD).

As further mentioned by the authors, a clear distinction was observed also between plasma samples when applying untargeted metabolomics, with TMAO being the top-ranking feature driving the differences found across the Fruitflow^® product group compared to the control group. Significant changes in microbial beta diversity were also highlighted. In addition, the microbiome composition changed significantly in the Fruitflow^® product group. Lower levels of Bacteroides, Ruminococccus and Hungatella were found, which are known for the involvement in TMA/TMAO metabolism. Dr. Steinert developed on the framework of these results within the overall gut-heart axis research: certainly, these results support earlier findings that polyphenol-rich extracts can lower TMAO concentrations and that this may be related to a targeted beneficial modulation of the gut microbiota. Dr. Claesson added: In this study, we identified set of bacteria that could possibly lower TMAO levels and can potentially be used as a targeted therapeutic strategy for treating cardiovascular disease. It has been proposed that species from the genus Bacteroides can convert TMAO to TMA. We found that the Bacteroides species namely, Bacteroides uniformis and Bacteroides ovatus and Bacteroides acidifaciens, were less abundant in Fruitflow^® product group compare to controls explaining observed effect on TMAO via reduction in Bacteroides species. We also noted a significant decrease in Rumonococcus faecis and Hungatella hathewayi within the Fruitflow^® product group. It is crucial to remember that Ruminococcus was discovered to have a positive correlation with plasma TMAO levels in a study on rats, while Hungatella hathewayi is known as a TMA producer.

The findings of this study are in line with the studies showing a reduction in plasma TMAO suggesting reproducible effects with polyphenol rich extracts. As a conclusion of this trial we could assert that polyphenol-rich extracts can modulate the gut microbiota conferring a host health benefit.