Intestinal Microbiota Composition Modulates Choline Bioavailability from Diet and Accumulation of the Proatherogenic Metabolite Trimethylamine- N -Oxide

Abstract

Choline is a water-soluble nutrient essential for human life. Gut microbial metabolism of choline results in the production of trimethylamine (TMA), which upon absorption by the host is converted in the liver to trimethylamine-N-oxide (TMAO). Recent studies revealed that TMAO exacerbates atherosclerosis in mice and positively correlates with the severity of this disease in humans. However, which microbes contribute to TMA production in the human gut, the extent to which host factors (e.g., genotype) and diet affect TMA production and colonization of these microbes, and the effects TMA-producing microbes have on the bioavailability of dietary choline remain largely unknown. We screened a collection of 79 sequenced human intestinal isolates encompassing the major phyla found in the human gut and identified nine strains capable of producing TMA from choline in vitro. Gnotobiotic mouse studies showed that TMAO accumulates in the serum of animals colonized with TMA-producing species, but not in the serum of animals colonized with intestinal isolates that do not generate TMA from choline in vitro. Remarkably, low levels of colonization by TMA-producing bacteria significantly reduced choline levels available to the host. This effect was more pronounced as the abundance of TMA-producing bacteria increased. Our findings provide a framework for designing strategies aimed at changing the representation or activity of TMA-producing bacteria in the human gut and suggest that the TMA-producing status of the gut microbiota should be considered when making recommendations about choline intake requirements for humans.

Comparing metabolite profiles of habitual diet in serum and urine

“…We found that TMAO was associated with added sugar intake (r = 0.23). Sucrose previously has been shown to modify the gut microbiome (46,47); thus, our findings possibly could indicate an indirect sugar effect on TMAO via changes to the gut microbiome.…”

Trimethylamine‐N‐oxide promotes brain aging and cognitive impairment in mice

“…TMAO, a metabolite of intestinal flora, was shown to be closely associated with age‐related diseases. The level of plasma TMAO can be influenced by several factors (Romano, Vivas, Amadornoguez & Rey, 2015), including gut microbiota, diet, liver FMO enzymes and kidney function. Previous studies have shown that aging can alter the structure and function of intestinal flora (O'Toole & Jeffery, 2015), especially in elderly people (>65 years of age) (Claesson et al., 2012).…”

Microbiology Meets Big Data: The Case of Gut Microbiota–Derived Trimethylamine

“…A resource of interest for large-scale epidemiological studies linking choline consumption and microbiome fluctuations to CVD risk is the US-targeted database for the content of choline-containing metabolites in common foods (http://www.ars.usda.gov/Services/docs.htm?docid=6232). Interestingly, in a recent study colonization of gnotobiotic mice with choline-converting bacteria not only increased cecal TMA production but also lowered choline serum concentrations (42). This suggests that the microbial TMA production potential should be taken into account when formulating dietary choline intake recommendations for humans.…”