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

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.

SUBMITTER: Wu WK

PROVIDER: S-EPMC7676756 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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

Wu Wei-Kai WK Panyod Suraphan S Liu Po-Yu PY Chen Chieh-Chang CC Kao Hsien-Li HL Chuang Hsiao-Li HL Chen Ying-Hsien YH Zou Hsin-Bai HB Kuo Han-Chun HC Kuo Ching-Hua CH Liao Ben-Yang BY Chiu Tina H T THT Chung Ching-Hu CH Lin Angela Yu-Chen AY Lee Yi-Chia YC Tang Sen-Lin SL Wang Jin-Town JT Wu Yu-Wei YW Hsu Cheng-Chih CC Sheen Lee-Yan LY Orekhov Alexander N AN Wu Ming-Shiang MS

Microbiome 20201119 1

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 wi ...[more]

PMID: 33213511

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Project description:Abstract Objectives A key to a successful personalized nutrition (PN) strategy is tailoring the behavior intervention to achieve sustained behavior change consistent with desired health outcomes. The objective of this study was to evaluate the impact of a digitally-delivered, systems biology-based PN program (Habit, LLC, Oakland, CA), that included nutrition and behavior advice, and meals. Methods In this single-arm, multi-phase, open-label study (clinicaltrials.gov: NCT03424395), participants (n = 107; 67% female), 30–59 years of age, were provided a Fitbit® Activity Tracker and instructions to complete an at-home kit that included collection of DNA and capillary blood before and after (30 and 120 min) consuming a mixed macronutrient challenge beverage. Lifestyle behavior data and activity levels were collected at baseline. Participants completed a 10-week control phase and a 10-week PN program intervention phase that included tailored nutrition and behavior advice, and meals (2 meals/day, 5 days/week). Validated quality of life, perceived stress, diet self-efficacy, and eating behavior questionnaires were administered to assess behavior before and after the intervention. Data from 73 compliant participants (66% female) were included in the analysis. Anthropometric and biological results were used to categorize participants into subgroups including Protein Seekers (PS) and Range Seekers (RS). Results Participants reported feeling fuller faster after the intervention, relative to before (P = 0.002), which could be linked to the dietary recommendations and behavior advice. Analysis by gender showed men reported more control over their eating patterns during negative events at baseline, compared to women (P = 0.005). This difference was not evident at the end of the intervention with women reporting slightly more, and men slightly less control. PS entered the study with a higher weight and BMI (P < 0.001 for both) and reported eating more quickly than RS (P = 0.003). This difference diminished, and by the end of the intervention PS did not differ from RS which could reflect the tailored advice provided. Conclusions These and other data provide novel insights on how a tailored personalized intervention that targeted food behavior may help drive positive changes in health outcomes. Funding Sources Habit, LLC.

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

Publications

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

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