Intestinal microbiota composition modulates choline bioavailability from diet and accumulation of the proatherogenic metabolite XXXX .

@entity1 @entity66 @entity19 @entity731 @entity204 @entity65 @entity942
Choline is a water-soluble nutrient essential for @entity1 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 @entity66 ( @entity66 ). Recent studies revealed that @entity66 exacerbates @entity731 in @entity19 and positively correlates with the severity of this disease in @entity1 . However, which microbes contribute to TMA production in the @entity1 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 @entity1 intestinal isolates encompassing the major phyla found in the @entity1 gut and identified nine strains capable of producing TMA from choline in vitro. Gnotobiotic @entity19 studies showed that @entity66 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 @entity1 gut and suggest that the TMA-producing status of the gut microbiota should be considered when making recommendations about choline intake requirements for @entity1 . IMPORTANCE: @entity65 ( @entity65 ) is the leading cause of @entity204 and disability worldwide, and increased @entity66 ( @entity66 ) levels have been causally linked with @entity65 development. This work identifies members of the @entity1 gut microbiota responsible for both the accumulation of trimethylamine (TMA), the precursor of the proatherogenic compound @entity66 , and subsequent decreased choline bioavailability to the host. Understanding how to manipulate the representation and function of choline-consuming, TMA-producing species in the intestinal microbiota could potentially lead to novel means for preventing or treating @entity731 and choline @entity942 .
