Characterization of TMAO productivity from carnitine challenge facilitates personalized nutrition and microbiome signatures discovery
Posted on 2020-11-20 - 15:02
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. timonensis and I. massiliensis could account for 43% of high TMAO producers with 97% specificity. Collectively, this human gut microbiota phenotype-directed approach offers potential for developing precision medicine and provides insights into translational research. Video Abstract
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Wu, Wei-Kai; Panyod, Suraphan; Liu, Po-Yu; Chen, Chieh-Chang; Kao, Hsien-Li; Chuang, Hsiao-Li; et al. (2020). Characterization of TMAO productivity from carnitine challenge facilitates personalized nutrition and microbiome signatures discovery. figshare. Collection. https://doi.org/10.6084/m9.figshare.c.5214059.v1
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AUTHORS (22)
WW
Wei-Kai Wu
SP
Suraphan Panyod
PL
Po-Yu Liu
CC
Chieh-Chang Chen
HK
Hsien-Li Kao
HC
Hsiao-Li Chuang
YC
Ying-Hsien Chen
HZ
Hsin-Bai Zou
HK
Han-Chun Kuo
CK
Ching-Hua Kuo
BL
Ben-Yang Liao
TC
Tina H. T. Chiu
CC
Ching-Hu Chung
AL
Angela Yu-Chen Lin
YL
Yi-Chia Lee
ST
Sen-Lin Tang
JW
Jin-Town Wang
YW
Yu-Wei Wu
CH
Cheng-Chih Hsu
LS
Lee-Yan Sheen