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.

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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 IDST002861
Study TitleGut Microbiota-associated Metabolites Affected the Susceptibility to Heart Health Abnormality in Young Migrants at High-altitude-Human Serum 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.
Institute
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
Emailjingjing2018@sjtu.edu.cn
Phone18818211315
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
https://dx.doi.org/10.21228/M8BD9J
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Project:

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
Email:jingjing2018@sjtu.edu.cn
Phone:18818211315

Subject:

Subject ID:SU002973
Subject Type:Human
Subject Species:Homo sapiens
Taxonomy ID:9606

Factors:

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

mb_sample_id local_sample_id Treatment
SA308976A_155high-altitude group
SA308977A_154high-altitude group
SA308978A_156high-altitude group
SA308979A_158high-altitude group
SA308980A_159high-altitude group
SA308981A_153high-altitude group
SA308982A_157high-altitude group
SA308983A_152high-altitude group
SA308984A_148high-altitude group
SA308985A_147high-altitude group
SA308986A_149high-altitude group
SA308987A_150high-altitude group
SA308988A_151high-altitude group
SA308989A_160high-altitude group
SA308990A_161high-altitude group
SA308991A_170high-altitude group
SA308992A_169high-altitude group
SA308993A_171high-altitude group
SA308994A_172high-altitude group
SA308995A_173high-altitude group
SA308996A_168high-altitude group
SA308997A_167high-altitude group
SA308998A_163high-altitude group
SA308999A_162high-altitude group
SA309000A_164high-altitude group
SA309001A_165high-altitude group
SA309002A_166high-altitude group
SA309003A_146high-altitude group
SA309004A_144high-altitude group
SA309005A_126high-altitude group
SA309006A_125high-altitude group
SA309007A_127high-altitude group
SA309008A_128high-altitude group
SA309009A_130high-altitude group
SA309010A_129high-altitude group
SA309011A_124high-altitude group
SA309012A_123high-altitude group
SA309013A_119high-altitude group
SA309014A_118high-altitude group
SA309015A_120high-altitude group
SA309016A_121high-altitude group
SA309017A_122high-altitude group
SA309018A_131high-altitude group
SA309019A_132high-altitude group
SA309020A_141high-altitude group
SA309021A_140high-altitude group
SA309022A_142high-altitude group
SA309023A_143high-altitude group
SA309024A_174high-altitude group
SA309025A_139high-altitude group
SA309026A_138high-altitude group
SA309027A_134high-altitude group
SA309028A_133high-altitude group
SA309029A_135high-altitude group
SA309030A_136high-altitude group
SA309031A_137high-altitude group
SA309032A_145high-altitude group
SA309033A_175high-altitude group
SA309034A_212high-altitude group
SA309035A_211high-altitude group
SA309036A_213high-altitude group
SA309037A_214high-altitude group
SA309038A_216high-altitude group
SA309039A_215high-altitude group
SA309040A_210high-altitude group
SA309041A_209high-altitude group
SA309042A_205high-altitude group
SA309043A_204high-altitude group
SA309044A_206high-altitude group
SA309045A_207high-altitude group
SA309046A_208high-altitude group
SA309047A_217high-altitude group
SA309048A_218high-altitude group
SA309049A_227high-altitude group
SA309050A_226high-altitude group
SA309051A_228high-altitude group
SA309052A_229high-altitude group
SA309053A_230high-altitude group
SA309054A_225high-altitude group
SA309055A_224high-altitude group
SA309056A_220high-altitude group
SA309057A_219high-altitude group
SA309058A_221high-altitude group
SA309059A_222high-altitude group
SA309060A_223high-altitude group
SA309061A_203high-altitude group
SA309062A_202high-altitude group
SA309063A_184high-altitude group
SA309064A_183high-altitude group
SA309065A_185high-altitude group
SA309066A_186high-altitude group
SA309067A_187high-altitude group
SA309068A_182high-altitude group
SA309069A_181high-altitude group
SA309070A_177high-altitude group
SA309071A_176high-altitude group
SA309072A_178high-altitude group
SA309073A_179high-altitude group
SA309074A_180high-altitude group
SA309075A_188high-altitude group
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Collection:

Collection ID:CO002966
Collection Summary:Blood samples were obtained from both groups using evacuated blood collection tubes (Becton Dickinson MEDICAL DEVICES (Shanghai) Co., Ltd). The samples were left undisturbed for 30 minutes and then subjected to centrifugation at 5000 rpm/min for 15 minutes at a temperature of 4℃. After centrifugation the serum samples were collected and stored at -80°C before use.
Sample Type:Serum

Treatment:

Treatment ID:TR002982
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: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.

Combined analysis:

Analysis ID AN004691 AN004692
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 Type ESI ESI
MS instrument type Triple quadrupole Triple quadrupole
MS instrument name Agilent 6495 QQQ Agilent 6495 QQQ
Ion Mode POSITIVE NEGATIVE
Units counts count

Chromatography:

Chromatography ID:CH003533
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:

MS ID:MS004438
Analysis ID:AN004691
Instrument Name:Agilent 6495 QQQ
Instrument Type:Triple quadrupole
MS Type:ESI
MS Comments:Agilent MassHunter Workstation Data Acquisition Agilent MassHunter
Ion Mode:POSITIVE
Analysis Protocol File:MS.pdf
  
MS ID:MS004439
Analysis ID:AN004692
Instrument Name:Agilent 6495 QQQ
Instrument Type:Triple quadrupole
MS Type:ESI
MS Comments:Agilent MassHunter Workstation Data Acquisition Agilent MassHunter
Ion Mode:NEGATIVE
Analysis Protocol File:MS.pdf
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