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Fecal Microbiome Composition Does Not Predict Diet-Induced TMAO Production in Healthy Adults.

ABSTRACT: Background Trimethylamine-N-oxide (TMAO) is a small molecule derived from the metabolism of dietary nutrients by gut microbes and contributes to cardiovascular disease. Plasma TMAO increases following consumption of red meat. This metabolic change is thought to be partly because of the expansion of gut microbes able to use nutrients abundant in red meat. Methods and Results We used data from a randomized crossover study to estimate the degree to which TMAO can be estimated from fecal microbial composition. Healthy participants received a series of 3 diets that differed in protein source (red meat, white meat, and non-meat), and fecal, plasma, and urine samples were collected following 4 weeks of exposure to each diet. TMAO was quantitated in plasma and urine, while shotgun metagenomic sequencing was performed on fecal DNA. While the cai gene cluster was weakly correlated with plasma TMAO (rho=0.17, P=0.0007), elastic net models of TMAO were not improved by abundances of bacterial genes known to contribute to TMAO synthesis. A global analysis of all taxonomic groups, genes, and gene families found no meaningful predictors of TMAO. We postulated that abundances of known genes related to TMAO production do not predict bacterial metabolism, and we measured choline- and carnitine-trimethylamine lyase activity during fecal culture. Trimethylamine lyase genes were only weakly correlated with the activity of the enzymes they encode. Conclusions Fecal microbiome composition does not predict systemic TMAO because, in this case, gene copy number does not predict bacterial metabolic activity. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01427855.

SUBMITTER: Ferrell M

PROVIDER: S-EPMC8751816 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:The gut microbiome has an important role in health, and diet represents a key lever for shaping the gut microbiome across all stages of life. Maternal milk consumption in neonates leads to long-term health effects, indicating that pliability in the infant gut microbiome in response to diet can drive enduring change. The ability of diet to drive lasting changes in the adult gut microbiome is less understood. We studied the effect of an extreme dietary shift on the fecal microbiome of 46 Labrador retriever dogs (mean age, 4.6 years) over 11 months. Dogs were fed a nutritionally complete, commercially available complex diet (CD) for a minimum of 5 weeks, followed by highly purified diets (PDs) for 36 weeks, and the initial CD for at least a further 4 weeks. Fecal samples were collected at regular intervals for DNA extraction. By analyzing 16S rRNA genes and the metagenomes, we observed minor effects on microbial diversity but significant changes in bacterial taxa and genetic potential when a PD was fed. Specifically, metagenomics identified an enrichment of quinone- and GABA-related pathways on PD, providing insights into dietary effects on cross-feeding strategies impacting community structure. When dogs returned to the CD, no significant differences were found with the initial time point. These findings are consistent with the gut microbiome being rapidly adaptable but capable of being reconstituted when provided with similar diets. These data highlight that long-term changes in the adult dog gut microbiome may only be achieved through long-term maintenance on a specified diet, rather than through feeding a transitionary diet.IMPORTANCE Diet can influence the adult gut microbiome (the community of bacteria) and health outcomes, but the ability to make changes persisting beyond feeding of a particular diet is poorly understood. We investigated whether feeding highly purified diets to adult dogs for 36 weeks would alter bacterial populations sufficiently to result in a persistent change following the dogs' return to a commercial diet. As expected, the microbiome changed when the purified diet was fed, but the original microbiome was reconstituted within weeks of the dogs returning to the commercial diet. The significance of these findings is in identifying an intrinsic stability of the host microbiome in healthy dogs, suggesting that dietary changes to support adult dog health through modifying the gut microbiome may be achieved only through maintenance on a specified diet, rather than through feeding transitionary diets.

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Fecal Microbiome Composition Does Not Predict Diet-Induced TMAO Production in Healthy Adults.

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