Characterization of TMAO productivity from carnitine challenge facilitates personalized nutrition and microbiome signatu
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RESEARCH
Open Access
Characterization of TMAO productivity from carnitine challenge facilitates personalized nutrition and microbiome signatures discovery Wei-Kai Wu1, Suraphan Panyod2†, Po-Yu Liu3†, Chieh-Chang Chen4†, Hsien-Li Kao4, Hsiao-Li Chuang5, Ying-Hsien Chen4, Hsin-Bai Zou6, Han-Chun Kuo7, Ching-Hua Kuo7,8, Ben-Yang Liao9, Tina H. T. Chiu10, Ching-Hu Chung11, Angela Yu-Chen Lin12, Yi-Chia Lee4, Sen-Lin Tang13, Jin-Town Wang4,14, Yu-Wei Wu15, Cheng-Chih Hsu6, Lee-Yan Sheen2, Alexander N. Orekhov16,17 and Ming-Shiang Wu3,4*
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. Keywords: Gut microbiome, Trimethylamine N-oxide, Oral carnitine challenge test, Personalized nutrition, Cardiovascular disease, Machine learning, Emergencia timonensis, Ihubacter massiliensis
* Correspondence: [email protected] † Suraphan Panyod, Po-Yu Liu and Chieh-Chang Chen contributed equally to this work. 3 Department of Internal Medicine, College of Medicine, National Taiwan University, No. 7, Chung-Shan South Road, Taipei 100, Taiwan 4 Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or ot
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