Summary of Study ST002862

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench,, 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.


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.

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Study IDST002862
Study TitleGut Microbiota-associated Metabolites Affected the Susceptibility to Heart Health Abnormality in Young Migrants at High-altitude-Human Faeces Metabolomics
Study SummaryBackground: 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.
Shanghai Center for Systems Biomedicine, Shanghai Jiaotong University
DepartmentShanghai Center for Systems Biomedicine
LaboratoryLu Group
Last NameLiu
First NameJingjing
Address800 Dongchuan RD. Minhang District, Shanghai, Shanghai, 200240, China
Submit Date2023-08-30
Raw Data AvailableYes
Raw Data File Type(s)d
Analysis Type DetailLC-MS
Release Date2023-09-27
Release Version1
Jingjing Liu Jingjing Liu application/zip

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Project ID:PR001790
Project DOI:doi: 10.21228/M8BD9J
Project Title:Gut Microbiota-associated Metabolites Affected the Susceptibility to Heart Health Abnormality in Young Migrants at High-altitude
Project Type:Targeted MS quantitative analysis
Project Summary:Characteristics of human serum and faeces metabolomics in the plateau migrants and plain controls
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


Subject ID:SU002974
Subject Type:Human
Subject Species:Homo sapiens
Taxonomy ID:9606


Subject type: Human; Subject species: Homo sapiens (Factor headings shown in green)

mb_sample_id local_sample_id Treatment
SA309206A_155high-altitude group
SA309207A_154high-altitude group
SA309208A_156high-altitude group
SA309209A_158high-altitude group
SA309210A_159high-altitude group
SA309211A_153high-altitude group
SA309212A_157high-altitude group
SA309213A_152high-altitude group
SA309214A_148high-altitude group
SA309215A_147high-altitude group
SA309216A_149high-altitude group
SA309217A_150high-altitude group
SA309218A_151high-altitude group
SA309219A_160high-altitude group
SA309220A_161high-altitude group
SA309221A_170high-altitude group
SA309222A_169high-altitude group
SA309223A_171high-altitude group
SA309224A_172high-altitude group
SA309225A_173high-altitude group
SA309226A_168high-altitude group
SA309227A_167high-altitude group
SA309228A_163high-altitude group
SA309229A_162high-altitude group
SA309230A_164high-altitude group
SA309231A_165high-altitude group
SA309232A_166high-altitude group
SA309233A_146high-altitude group
SA309234A_144high-altitude group
SA309235A_126high-altitude group
SA309236A_125high-altitude group
SA309237A_127high-altitude group
SA309238A_128high-altitude group
SA309239A_130high-altitude group
SA309240A_129high-altitude group
SA309241A_124high-altitude group
SA309242A_123high-altitude group
SA309243A_119high-altitude group
SA309244A_118high-altitude group
SA309245A_120high-altitude group
SA309246A_121high-altitude group
SA309247A_122high-altitude group
SA309248A_131high-altitude group
SA309249A_132high-altitude group
SA309250A_141high-altitude group
SA309251A_140high-altitude group
SA309252A_142high-altitude group
SA309253A_143high-altitude group
SA309254A_174high-altitude group
SA309255A_139high-altitude group
SA309256A_138high-altitude group
SA309257A_134high-altitude group
SA309258A_133high-altitude group
SA309259A_135high-altitude group
SA309260A_136high-altitude group
SA309261A_137high-altitude group
SA309262A_145high-altitude group
SA309263A_175high-altitude group
SA309264A_212high-altitude group
SA309265A_211high-altitude group
SA309266A_213high-altitude group
SA309267A_214high-altitude group
SA309268A_216high-altitude group
SA309269A_215high-altitude group
SA309270A_210high-altitude group
SA309271A_209high-altitude group
SA309272A_205high-altitude group
SA309273A_204high-altitude group
SA309274A_206high-altitude group
SA309275A_207high-altitude group
SA309276A_208high-altitude group
SA309277A_217high-altitude group
SA309278A_218high-altitude group
SA309279A_227high-altitude group
SA309280A_226high-altitude group
SA309281A_228high-altitude group
SA309282A_229high-altitude group
SA309283A_230high-altitude group
SA309284A_225high-altitude group
SA309285A_224high-altitude group
SA309286A_220high-altitude group
SA309287A_219high-altitude group
SA309288A_221high-altitude group
SA309289A_222high-altitude group
SA309290A_223high-altitude group
SA309291A_203high-altitude group
SA309292A_202high-altitude group
SA309293A_184high-altitude group
SA309294A_183high-altitude group
SA309295A_185high-altitude group
SA309296A_186high-altitude group
SA309297A_187high-altitude group
SA309298A_182high-altitude group
SA309299A_181high-altitude group
SA309300A_177high-altitude group
SA309301A_176high-altitude group
SA309302A_178high-altitude group
SA309303A_179high-altitude group
SA309304A_180high-altitude group
SA309305A_188high-altitude group
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Collection ID:CO002967
Collection Summary:Fecal samples were collected from participants using fecal sampling tubes (Shenzhen Medico Biomedical Technology Co., Ltd) and were also stored at -80°C after sampling.
Sample Type:Feces


Treatment ID:TR002983
Treatment Summary:The study enrolled two distinct groups: a plain group (PL) comprising 67 adult males from the Chengdu plain in Sichuan, and a high-altitude group (HA) comprising 163 adult males from Tibet residing at altitudes ranging from 3500m to 4500m. They were all graduated from Chengdu Medical College and enrolled in this study with the patients' consent and the sampling process was strictly consistent.The study received approval from the Ethics Committee of the Academy of Military Medicine, Chinese Academy of Military Sciences, with the approval number AF/SC-08/02.153.

Sample Preparation:

Sampleprep ID:SP002980
Sampleprep Summary:For fecal samples, 60mg of the sample was mixed with 600μL of 80% iced methanol, which included 0.001mg/mL 4-chloro-DL-phenylalanine as an internal standard. Zirconia crushing beads were added to the mixture, and the samples were disrupted using a vibratory crusher operating at 60 hertz. Subsequently, the samples were processed by ultrasonication in an ice bath for 10 minutes and left to stand at -20℃ for 30 minutes. The supernatants were collected by centrifugation at 20,000 g under 4 C for 10 minutes and then mixed with three-fold volumes of distilled water. After ultrasonication for 3 minutes to ensure even mixing, the samples were placed in a -20℃ environment for 2 hours. Finally, the supernatants obtained from centrifugation were transferred to sample vials for metabolomics analysis

Combined analysis:

Analysis ID AN004693 AN004694
Analysis type MS MS
Chromatography type Reversed phase Reversed phase
Chromatography system Agilent 1290 Infinity Agilent 1290 Infinity
Column Waters ACQUITY UPLC HSS T3 (100 x 2.1mm,1.8um) Waters ACQUITY UPLC HSS T3 (100 x 2.1mm,1.8um)
MS instrument type Triple quadrupole Triple quadrupole
MS instrument name Agilent 6495 QQQ Agilent 6495 QQQ
Units counts counts


Chromatography ID:CH003534
Chromatography Summary:In this study, a newly developed precision-targeted metabolomics method with a UPLC-TQ/MS system (Agilent 1290 Infnity, Agilent Technologies, USA; Agilent 6495 QQQ, Agilent Technologies, USA) in a DMRM scan-mode was applied to analyze the metabolome of interest from trial samples (serum, liver tissues and stool). Briefly, the method was performed with an ACQUITY UPLC HSS T3 column (2.1 mm i.d. × 100 mm, 1.8 μm; Waters); mobile phase A and B were water and acetonitrile with 0.1% formic acid (v/v) respectively. The flow rate was at 0.3 mL/min and the column temperature was maintained at 40 ℃. The samples were placed in an auto-sampler maintained at 4 °C with a 5 μL injection volume. The optimized gradient-elution program, as follows: 0-2 min, 98% A; 2-10 min, 98-65% A; 10-12 min, 65-20% A; 12-14 min, 20-2% A; 14-30 min, 2% A.
Methods Filename:Chromatography.pdf
Instrument Name:Agilent 1290 Infinity
Column Name:Waters ACQUITY UPLC HSS T3 (100 x 2.1mm,1.8um)
Column Temperature:40 ℃
Flow Gradient:0-2 minutes, 98% A 2-10 minutes, 98%-65% A 10-12 minutes, 65%-20% A 12-14 minutes, 20%-2% A 14-30 minutes, 2% A.
Flow Rate:0.3 ml/min
Solvent A:100% water + 0.1% formic acid
Solvent B:100% acetonitrile + 0.1% formic acid
Chromatography Type:Reversed phase


MS ID:MS004440
Analysis ID:AN004693
Instrument Name:Agilent 6495 QQQ
Instrument Type:Triple quadrupole
MS Comments:Agilent MassHunter Workstation Data Acquisition Agilent MassHunter
Analysis Protocol File:MS.pdf
MS ID:MS004441
Analysis ID:AN004694
Instrument Name:Agilent 6495 QQQ
Instrument Type:Triple quadrupole
MS Comments:Agilent MassHunter Workstation Data Acquisition Agilent MassHunter
Analysis Protocol File:MS.pdf