Summary of Study ST002862
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 | ST002862 |
| Study Title | Gut Microbiota-associated Metabolites Affected the Susceptibility to Heart Health Abnormality in Young Migrants at High-altitude-Human Faeces 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 |
| 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 |
Select appropriate tab below to view additional metadata details:
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: | SU002974 |
| 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 |
|---|---|---|
| SA309206 | A_155 | high-altitude group |
| SA309207 | A_154 | high-altitude group |
| SA309208 | A_156 | high-altitude group |
| SA309209 | A_158 | high-altitude group |
| SA309210 | A_159 | high-altitude group |
| SA309211 | A_153 | high-altitude group |
| SA309212 | A_157 | high-altitude group |
| SA309213 | A_152 | high-altitude group |
| SA309214 | A_148 | high-altitude group |
| SA309215 | A_147 | high-altitude group |
| SA309216 | A_149 | high-altitude group |
| SA309217 | A_150 | high-altitude group |
| SA309218 | A_151 | high-altitude group |
| SA309219 | A_160 | high-altitude group |
| SA309220 | A_161 | high-altitude group |
| SA309221 | A_170 | high-altitude group |
| SA309222 | A_169 | high-altitude group |
| SA309223 | A_171 | high-altitude group |
| SA309224 | A_172 | high-altitude group |
| SA309225 | A_173 | high-altitude group |
| SA309226 | A_168 | high-altitude group |
| SA309227 | A_167 | high-altitude group |
| SA309228 | A_163 | high-altitude group |
| SA309229 | A_162 | high-altitude group |
| SA309230 | A_164 | high-altitude group |
| SA309231 | A_165 | high-altitude group |
| SA309232 | A_166 | high-altitude group |
| SA309233 | A_146 | high-altitude group |
| SA309234 | A_144 | high-altitude group |
| SA309235 | A_126 | high-altitude group |
| SA309236 | A_125 | high-altitude group |
| SA309237 | A_127 | high-altitude group |
| SA309238 | A_128 | high-altitude group |
| SA309239 | A_130 | high-altitude group |
| SA309240 | A_129 | high-altitude group |
| SA309241 | A_124 | high-altitude group |
| SA309242 | A_123 | high-altitude group |
| SA309243 | A_119 | high-altitude group |
| SA309244 | A_118 | high-altitude group |
| SA309245 | A_120 | high-altitude group |
| SA309246 | A_121 | high-altitude group |
| SA309247 | A_122 | high-altitude group |
| SA309248 | A_131 | high-altitude group |
| SA309249 | A_132 | high-altitude group |
| SA309250 | A_141 | high-altitude group |
| SA309251 | A_140 | high-altitude group |
| SA309252 | A_142 | high-altitude group |
| SA309253 | A_143 | high-altitude group |
| SA309254 | A_174 | high-altitude group |
| SA309255 | A_139 | high-altitude group |
| SA309256 | A_138 | high-altitude group |
| SA309257 | A_134 | high-altitude group |
| SA309258 | A_133 | high-altitude group |
| SA309259 | A_135 | high-altitude group |
| SA309260 | A_136 | high-altitude group |
| SA309261 | A_137 | high-altitude group |
| SA309262 | A_145 | high-altitude group |
| SA309263 | A_175 | high-altitude group |
| SA309264 | A_212 | high-altitude group |
| SA309265 | A_211 | high-altitude group |
| SA309266 | A_213 | high-altitude group |
| SA309267 | A_214 | high-altitude group |
| SA309268 | A_216 | high-altitude group |
| SA309269 | A_215 | high-altitude group |
| SA309270 | A_210 | high-altitude group |
| SA309271 | A_209 | high-altitude group |
| SA309272 | A_205 | high-altitude group |
| SA309273 | A_204 | high-altitude group |
| SA309274 | A_206 | high-altitude group |
| SA309275 | A_207 | high-altitude group |
| SA309276 | A_208 | high-altitude group |
| SA309277 | A_217 | high-altitude group |
| SA309278 | A_218 | high-altitude group |
| SA309279 | A_227 | high-altitude group |
| SA309280 | A_226 | high-altitude group |
| SA309281 | A_228 | high-altitude group |
| SA309282 | A_229 | high-altitude group |
| SA309283 | A_230 | high-altitude group |
| SA309284 | A_225 | high-altitude group |
| SA309285 | A_224 | high-altitude group |
| SA309286 | A_220 | high-altitude group |
| SA309287 | A_219 | high-altitude group |
| SA309288 | A_221 | high-altitude group |
| SA309289 | A_222 | high-altitude group |
| SA309290 | A_223 | high-altitude group |
| SA309291 | A_203 | high-altitude group |
| SA309292 | A_202 | high-altitude group |
| SA309293 | A_184 | high-altitude group |
| SA309294 | A_183 | high-altitude group |
| SA309295 | A_185 | high-altitude group |
| SA309296 | A_186 | high-altitude group |
| SA309297 | A_187 | high-altitude group |
| SA309298 | A_182 | high-altitude group |
| SA309299 | A_181 | high-altitude group |
| SA309300 | A_177 | high-altitude group |
| SA309301 | A_176 | high-altitude group |
| SA309302 | A_178 | high-altitude group |
| SA309303 | A_179 | high-altitude group |
| SA309304 | A_180 | high-altitude group |
| SA309305 | A_188 | high-altitude group |
Collection:
| 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:
| 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 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 | counts |
Chromatography:
| 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:
| MS ID: | MS004440 |
| Analysis ID: | AN004693 |
| 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: | MS004441 |
| Analysis ID: | AN004694 |
| 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 |
