Summary of Study ST002861

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001790. The data can be accessed directly via it's Project DOI: 10.21228/M8BD9J This work is supported by NIH grant, U2C- DK119886.

See: https://www.metabolomicsworkbench.org/about/howtocite.php

This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.

Study ID	ST002861
Study Title	Gut Microbiota-associated Metabolites Affected the Susceptibility to Heart Health Abnormality in Young Migrants at High-altitude-Human Serum Metabolomics
Study Summary	Background: Young migrants in plateau are susceptible to heart health abnormality and even high-altitude heart disease (HAHD). Though the gut microbial community was found to be drastically affected when exposed to a hypobaric hypoxia environment, there is limited knowledge about the roles of gut microbiota and gut microbiota-associated serum metabolites (GMSMs) in high-altitude associated heart diseases. Hence, we performed multi-omics integration analysis of 230 graduates from the same university in this study (163 who migrated to Tibet Plateau and 67 matched controls currently living in Chengdu Plain) to explore how the gut microbiota affect the development of high-altitude associated heart health abnormality. Results: Here, we found 206 differential metabolites (82 from serum and 124 from feces) and 369 differential species among the plateau migrants and plain controls. Of these, 27 differential microbial species and 4 differential metabolites (L-Asp, betaine, 3-GUA, and α-KG) that both existed in serum and feces were related to the plateau migrants with undermined heart health (HH-A), which were diagnosed by biomedical detection, electrocardiography (ECG), frequency-domain Cardiogram (FCG) and ultrasonic cardiogram (UCG). Moreover, the abundances of Streptococcus rubneri and Veillonella rogosae were related with the serum levels of L-Asp, betaine, and α-KG in HH-A individuals. And lower these microbiome biomarkers and GMSMs abundances were validated in an independent cohort, both of which together had an excellent discernibility efficacy of heart health abnormality in plateau migrants, with a higher AUC value of 0.7857. Besides, supplement with the two species or each of GMSMs were confirmed to effectively attenuate hypobaric hypoxia-induced higher serum lactic acid, glycolysis, myocardial damage and cardiac hypertrophy. Integrated analysis revealed significant shift in gut microbiome exerted negative regulations in Malate-Aspartate (MA) shuttle, Tricarboxylic acid cycle (TCA) and oxidative phosphorylation in HH-A individuals. Conclusion: Plateau migration altered profoundly the signatures of gut microbiome and metabolome in young migrants. Hypobaric hypoxia-induced lower abundances of Veillonella rogosae, Streptococcus rubneri, and related GMSMs promoted the remodeling of metabolic processes, resulting in higher susceptibility to heart health abnormality in high-altitude. Our findings not only presented elaborate microbial mechanisms, but also provided potential early risk prediction and therapeutic interventions for HAHD.
Institute	Shanghai Center for Systems Biomedicine, Shanghai Jiaotong University
Department	Shanghai Center for Systems Biomedicine
Laboratory	Lu Group
Last Name	Liu
First Name	Jingjing
Address	800 Dongchuan RD. Minhang District, Shanghai, Shanghai, 200240, China
Email	jingjing2018@sjtu.edu.cn
Phone	18818211315
Submit Date	2023-08-30
Raw Data Available	Yes
Raw Data File Type(s)	d
Analysis Type Detail	LC-MS
Release Date	2023-09-27
Release Version	1

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Sample Preparation:

Sampleprep ID:	SP002979
Sampleprep Summary:	The serum samples were mixed with 4-fold volumes of iced acetonitrile, which included 0.001mg/mL 4-chloro-DL-phenylalanine as an internal standard. The mixture was incubated on ice for 15 minutes to facilitate protein removal. Following centrifugation at 20,000 g at 4°C for 10 minutes, the supernatants were carefully collected into new microcentrifuge tubes. After another round of centrifugation under the same conditions, the samples were transferred to sample vials for metabolomics analysis.

Sampleprep ID:

SP002979

Sampleprep Summary:

The serum samples were mixed with 4-fold volumes of iced acetonitrile, which included 0.001mg/mL 4-chloro-DL-phenylalanine as an internal standard. The mixture was incubated on ice for 15 minutes to facilitate protein removal. Following centrifugation at 20,000 g at 4°C for 10 minutes, the supernatants were carefully collected into new microcentrifuge tubes. After another round of centrifugation under the same conditions, the samples were transferred to sample vials for metabolomics analysis.