Characterization of TMAO productivity from carnitine challenge facilitates personalized nutrition and microbiome signatures discovery.

Microbiome
Wei-Kai WuMing-Shiang Wu

Abstract

The capability of gut microbiota in degrading foods and drugs administered orally can result in diversified efficacies and toxicity interpersonally and cause significant impact on human health. Production of atherogenic trimethylamine N-oxide (TMAO) from carnitine is a gut microbiota-directed pathway and varies widely among individuals. Here, we demonstrated a personalized TMAO formation and carnitine bioavailability from carnitine supplements by differentiating individual TMAO productivities with a recently developed oral carnitine challenge test (OCCT). By exploring gut microbiome in subjects characterized by TMAO producer phenotypes, we identified 39 operational taxonomy units that were highly correlated to TMAO productivity, including Emergencia timonensis, which has been recently discovered to convert γ-butyrobetaine to TMA in vitro. A microbiome-based random forest classifier was therefore constructed to predict the TMAO producer phenotype (AUROC = 0.81) which was then validated with an external cohort (AUROC = 0.80). A novel bacterium called Ihubacter massiliensis was also discovered to be a key microbe for TMA/TMAO production by using an OCCT-based humanized gnotobiotic mice model. Simply combining the presence of E. ti...Continue Reading

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Citations

Jul 2, 2020·Seminars in Cancer Biology·Wei-Kai WuAlexander N Orekhov
Jun 29, 2021·Gut Microbes·Jennifer Y ChoAnsel Hsiao
Aug 8, 2021·Proceedings of the National Academy of Sciences of the United States of America·Lauren J RajakovichEmily P Balskus
Aug 17, 2021·Journal of Agricultural and Food Chemistry·Ying Qi GohYulan Wang

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Methods Mentioned

BETA
Illumina
PCR

Clinical Trials Mentioned

NCT02838732
NCT03781011

Software Mentioned

Phylogeny
MiSeq
MUSCLE
ROCR
PhyML
R package vegan
Gblocks
ADONIS
fossil
R

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