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.

中文翻译：

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肉碱攻击对TMAO生产力的表征有助于个性化营养和微生物组特征的发现

肠道菌群降解口服食品和药物的能力会导致人际关系的多种功效和毒性，并对人体健康产生重大影响。由肉碱生产致动脉粥样硬化的三甲胺N-氧化物（TMAO）是肠道菌群控制的途径，在个体之间差异很大。在这里，我们通过使用最近开发的口服肉碱攻击试验（OCCT）来区分个体TMAO的生产力，从肉碱补充剂中展示了个性化的TMAO形成和肉碱的生物利用度。通过在以TMAO生产者表型为特征的受试者中研究肠道微生物组，我们确定了39个与TMAO生产力高度相关的操作分类单位，包括Emergencia timonensis，最近已发现它可以在体外将γ-丁甜菜碱转化为TMA。因此，构建了基于微生物组的随机森林分类器，以预测TMAO生产者表型（AUROC = 0.81），然后通过外部队列（AUROC = 0.80）对其进行验证。通过使用基于OCCT的人源化gnotobiotic小鼠模型，还发现了一种名为马氏Ihubacter的新型细菌，它是TMA / TMAO生产的关键微生物。简单地将timonensis和I. massiliensis的存在结合起来，可以构成高TMAO生产者的43％，特异性为97％。总的来说，这种以人肠道菌群为表型的方法为开发精密医学提供了潜力，并为转化研究提供了见识。通过使用基于OCCT的人源化gnotobiotic小鼠模型，还发现了一种名为马氏Ihubacter的新型细菌，它是TMA / TMAO生产的关键微生物。简单地将timonensis和I. massiliensis的存在结合起来，可以构成高TMAO生产者的43％，特异性为97％。总的来说，这种以人肠道菌群为表型的方法为开发精密医学提供了潜力，并为转化研究提供了见识。通过使用基于OCCT的人源化gnotobiotic小鼠模型，还发现了一种名为马氏Ihubacter的新型细菌，它是TMA / TMAO生产的关键微生物。简单地将timonensis和I. massiliensis的存在结合起来，可以构成高TMAO生产者的43％，特异性为97％。总的来说，这种以人肠道菌群为表型的方法为开发精密医学提供了潜力，并为转化研究提供了见识。