Summary of Study ST004248

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 PR002678. The data can be accessed directly via it's Project DOI: 10.21228/M8GZ65 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.

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Study IDST004248
Study TitleA multi-omics exploration of biological responses upon high carotenoid intake
Study SummaryScope Despite decades of research, aspects of the bioactive properties of carotenoids in vivo remain confounded by our limited understanding of their metabolic fates. Unbiased, systems-level approaches can help capture global metabolic shifts associated with carotenoid-rich diets. Here, we present an exploratory multi-omics integration–combining carotenoid/apocarotenoid concentrations, untargeted lipidomics, and transcriptomics–to elucidate the biological effects of tomato juices differing in b-carotene and lycopene content. Methods and results This study leverages blood samples from a previously conducted 4-week controlled parallel arm clinical trial. Thirty-five healthy adults on standardized background diets consumed daily 360 mL high lycopene tomato juice (42.5 mg lycopene/d), high b-carotene tomato juice (30.4 mg b-carotene/d), or a macronutrient-matched control. Plasma (apo)carotenoids and lipid profiles pre- and post-intervention were assessed, along with whole blood transcriptomes sequenced at week 4 only. Pairwise correlations and multiblock sparse-PLS-DA were utilized for multi-omics integration. Gene-set enrichment revealed carotenoid-specific modulation of transcripts related to immune function. Thirteen lipidomic features were significantly altered after b-carotene intake versus 2 upon high lycopene intake. Multi-omics integration resolved treatment groups, visualizing the distinct molecular signatures altered by two high carotenoid diets. This approach revealed subtle biological shifts are largely impacted by b-apo-13-carotenone levels. We document its inverse relationship with retinoic acid receptors and its downstream genes for the first time in humans, consistent with in vitro reports that b-apo-13-carotenone is an antagonist for retinoic acid signaling. Conclusion Multi-omics integration uncovers testable, hypothesis-generating insights about carotenoid metabolism and how metabolites may modulate molecular signaling pathways in humans.
Institute
Ohio State University
DepartmentFood Science & Technology
LaboratoryCooperstone Lab
Last NameSholola
First NameMaria
Address2255 Kenny Rd
Emailsholola.1@osu.edu
Phone17086463488
Submit Date2025-09-23
Num Groups3
Total Subjects35
Num Males17
Num Females18
Raw Data AvailableYes
Raw Data File Type(s)d, mzML
Analysis Type DetailLC-MS
Release Date2025-10-22
Release Version1
Maria Sholola Maria Sholola
https://dx.doi.org/10.21228/M8GZ65
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Project:

Project ID:PR002678
Project DOI:doi: 10.21228/M8GZ65
Project Title:A multi-omics exploration of biological responses upon high carotenoid intake
Project Summary:Scope Despite decades of research, aspects of the bioactive properties of carotenoids in vivo remain confounded by our limited understanding of their metabolic fates. Unbiased, systems-level approaches can help capture global metabolic shifts associated with carotenoid-rich diets. Here, we present an exploratory multi-omics integration–combining carotenoid/apocarotenoid concentrations, untargeted lipidomics, and transcriptomics–to elucidate the biological effects of tomato juices differing in b-carotene and lycopene content. Methods and results This study leverages blood samples from a previously conducted 4-week controlled parallel arm clinical trial. Thirty-five healthy adults on standardized background diets consumed daily 360 mL high lycopene tomato juice (42.5 mg lycopene/d), high b-carotene tomato juice (30.4 mg b-carotene/d), or a macronutrient-matched control. Plasma (apo)carotenoids and lipid profiles pre- and post-intervention were assessed, along with whole blood transcriptomes sequenced at week 4 only. Pairwise correlations and multiblock sparse-PLS-DA were utilized for multi-omics integration. Gene-set enrichment revealed carotenoid-specific modulation of transcripts related to immune function. Thirteen lipidomic features were significantly altered after b-carotene intake versus 2 upon high lycopene intake. Multi-omics integration resolved treatment groups, visualizing the distinct molecular signatures altered by two high carotenoid diets. This approach revealed subtle biological shifts are largely impacted by b-apo-13-carotenone levels. We document its inverse relationship with retinoic acid receptors and its downstream genes for the first time in humans, consistent with in vitro reports that b-apo-13-carotenone is an antagonist for retinoic acid signaling. Conclusion Multi-omics integration uncovers testable, hypothesis-generating insights about carotenoid metabolism and how metabolites may modulate molecular signaling pathways in humans.
Institute:Ohio State University
Department:Food Science & Technology
Laboratory:Cooperstone Lab
Last Name:Sholola
First Name:Maria
Address:2255 Kenny Rd
Email:sholola.1@osu.edu
Phone:7086463488

Subject:

Subject ID:SU004400
Subject Type:Human
Subject Species:Homo sapiens
Taxonomy ID:9606
Age Or Age Range:21-75
Gender:Male and female
Human Inclusion Criteria:Subjects were required to have blood glucose <126 mg/dL and triglycerides <300 mg/dL
Human Exclusion Criteria:Subjects were excluded if any of the following were present: cancer, type 2 diabetes, gastrointestinal surgeries or malabsorptive disorders, metabolic disease, pregnancy or currently lactating, or use of blood thinning medications

Factors:

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

mb_sample_id local_sample_id Sample source Timepoint
SA496246qc8_c18neg_43blood plasma pooled quality control
SA496247qc1_c18neg_1blood plasma pooled quality control
SA496248qc1_c18pos_1blood plasma pooled quality control
SA496249qc2_c18neg_7blood plasma pooled quality control
SA496250qc2_c18pos_7blood plasma pooled quality control
SA496251qc3_c18neg_13blood plasma pooled quality control
SA496252qc3_c18pos_13blood plasma pooled quality control
SA496253qc4_c18neg_19blood plasma pooled quality control
SA496254qc4_c18pos_19blood plasma pooled quality control
SA496255qc5_c18pos_25blood plasma pooled quality control
SA496256qc6_c18neg_31blood plasma pooled quality control
SA496257qc6_c18pos_31blood plasma pooled quality control
SA496258qc7_c18neg_37blood plasma pooled quality control
SA496259qc7_c18pos_37blood plasma pooled quality control
SA496260qc5_c18neg_25blood plasma pooled quality control
SA496261qc8_c18pos_43blood plasma pooled quality control
SA496262qc12_c18pos_67blood plasma pooled quality control
SA496263qc9_c18neg_49blood plasma pooled quality control
SA496264qc15_c18neg_85blood plasma pooled quality control
SA496265qc14_c18pos_79blood plasma pooled quality control
SA496266qc14_c18neg_79blood plasma pooled quality control
SA496267qc13_c18pos_73blood plasma pooled quality control
SA496268qc13_c18neg_73blood plasma pooled quality control
SA496269qc15_c18pos_85blood plasma pooled quality control
SA496270qc12_c18neg_67blood plasma pooled quality control
SA496271qc11_c18pos_61blood plasma pooled quality control
SA496272qc11_c18neg_61blood plasma pooled quality control
SA496273qc10_c18pos_55blood plasma pooled quality control
SA496274qc10_c18neg_55blood plasma pooled quality control
SA496275qc9_c18pos_49blood plasma pooled quality control
SA4962765114-b3-beta_c18neg_23blood plasma post beta
SA4962775132-b3-beta_c18pos_52blood plasma post beta
SA4962785134-b3-beta_c18pos_64blood plasma post beta
SA4962795136-b3-beta_c18pos_77blood plasma post beta
SA4962805107-b3-beta_c18neg_28blood plasma post beta
SA4962815112-b3-beta_c18neg_56blood plasma post beta
SA4962825113-b3-beta_c18neg_47blood plasma post beta
SA4962835126-b3-beta_c18neg_24blood plasma post beta
SA4962845120-b3-beta_c18neg_54blood plasma post beta
SA4962855121-b3-beta_c18neg_48blood plasma post beta
SA4962865126-b3-beta_c18pos_24blood plasma post beta
SA4962875131-b3-beta_c18neg_3blood plasma post beta
SA4962885132-b3-beta_c18neg_52blood plasma post beta
SA4962895134-b3-beta_c18neg_64blood plasma post beta
SA4962905136-b3-beta_c18neg_77blood plasma post beta
SA4962915131-b3-beta_c18pos_3blood plasma post beta
SA4962925109-b3-beta_c18neg_81blood plasma post beta
SA4962935120-b3-beta_c18pos_54blood plasma post beta
SA4962945121-b3-beta_c18pos_48blood plasma post beta
SA4962955112-b3-beta_c18pos_56blood plasma post beta
SA4962965107-b3-beta_c18pos_28blood plasma post beta
SA4962975113-b3-beta_c18pos_47blood plasma post beta
SA4962985109-b3-beta_c18pos_81blood plasma post beta
SA4962995114-b3-beta_c18pos_23blood plasma post beta
SA4963005133-b3-control_c18neg_15blood plasma post control
SA4963015111-b3-control_c18pos_39blood plasma post control
SA4963025123-b3-control_c18neg_40blood plasma post control
SA4963035116-b3-control_c18pos_20blood plasma post control
SA4963045111-b3-control_c18neg_39blood plasma post control
SA4963055102-b3-control_c18neg_33blood plasma post control
SA4963065101-b3-control_c18neg_66blood plasma post control
SA4963075108-b3-control_c18neg_22blood plasma post control
SA4963085123-b3-control_c18pos_40blood plasma post control
SA4963095119-b3-control_c18pos_58blood plasma post control
SA4963105116-b3-control_c18neg_20blood plasma post control
SA4963115101-b3-control_c18pos_66blood plasma post control
SA4963125119-b3-control_c18neg_58blood plasma post control
SA4963135102-b3-control_c18pos_33blood plasma post control
SA4963145127-b3-control_c18pos_83blood plasma post control
SA4963155124-b3-control_c18neg_68blood plasma post control
SA4963165125-b3-control_c18pos_51blood plasma post control
SA4963175125-b3-control_c18neg_51blood plasma post control
SA4963185127-b3-control_c18neg_83blood plasma post control
SA4963195124-b3-control_c18pos_68blood plasma post control
SA4963205108-b3-control_c18pos_22blood plasma post control
SA4963215133-b3-control_c18pos_15blood plasma post control
SA4963225128-b3-lyc_c18neg_60blood plasma post red
SA4963235118-b3-lyc_c18neg_9blood plasma post red
SA4963245110-b3-lyc_c18neg_84blood plasma post red
SA4963255115-b3-lyc_c18neg_70blood plasma post red
SA4963265122-b3-lyc_c18pos_75blood plasma post red
SA4963275117-b3-lyc_c18neg_2blood plasma post red
SA4963285130-b3-lyc_c18neg_50blood plasma post red
SA4963295118-b3-lyc_c18pos_9blood plasma post red
SA4963305129-b3-lyc_c18neg_16blood plasma post red
SA4963315115-b3-lyc_c18pos_70blood plasma post red
SA4963325135-b3-lyc_c18neg_18blood plasma post red
SA4963335110-b3-lyc_c18pos_84blood plasma post red
SA4963345103-b3-lyc_c18pos_63blood plasma post red
SA4963355128-b3-lyc_c18pos_60blood plasma post red
SA4963365104-b3-lyc_c18pos_32blood plasma post red
SA4963375129-b3-lyc_c18pos_16blood plasma post red
SA4963385105-b3-lyc_c18pos_21blood plasma post red
SA4963395130-b3-lyc_c18pos_50blood plasma post red
SA4963405135-b3-lyc_c18pos_18blood plasma post red
SA4963415103-b3-lyc_c18neg_63blood plasma post red
SA4963425104-b3-lyc_c18neg_32blood plasma post red
SA4963435105-b3-lyc_c18neg_21blood plasma post red
SA4963445117-b3-lyc_c18pos_2blood plasma post red
SA4963455122-b3-lyc_c18neg_75blood plasma post red
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Collection:

Collection ID:CO004393
Collection Summary:This study leveraged blood samples from a previously conducted parallel-arm clinical trial (NCT2550483).
Sample Type:Blood (plasma)

Treatment:

Treatment ID:TR004409
Treatment Summary:The intervention was a high-lycopene (red) tomato juice or a high-β-carotene (orange) tomato juice, both derived from inbred tomato lines developed through conventional breeding. Thirty-five healthy adults on standardized background diets consumed daily 360 mL high lycopene tomato juice (42.5 mg lycopene/d), high b-carotene tomato juice (30.4 mg b-carotene/d), or a macronutrient-matched control. Plasma (apo)carotenoids and lipid profiles pre- and post-intervention were assessed, along with whole blood transcriptomes sequenced at week 4 only.

Sample Preparation:

Sampleprep ID:SP004406
Sampleprep Summary:In low light, blood plasma samples were thawed in cold water and vortexed to ensure redistribution of lipids prior to extraction. Fifty microliters of thawed plasma samples were transferred into centrifuge tubes, followed by an addition of 250 microliters cold methanol with 10 mM ammonium formate to precipitate proteins. Samples were then homogenized in a GenoGrinder 2010 (SPEX Sample Prep, Metuchen, NJ, USA) for 2 min at 1400 RPM, and 250 microliters of butanol with 10 mM ammonium formate was added to each sample. Extracts were centrifuged at 13,000 x g for 10 min at 4 deg C. Process blanks were prepared with water replacing the plasma and following the same steps while quality control (QC) samples were made by pooling 50 microliters from each plasma sample at the end of extraction. This method was adapted from Huynh and colleagues (doi: 10.1016/j.chembiol.2018.10.008)

Combined analysis:

Analysis ID AN007070 AN007071
Chromatography ID CH005368 CH005368
MS ID MS006767 MS006768
Analysis type MS MS
Chromatography type Reversed phase Reversed phase
Chromatography system Agilent 1290 Infinity Agilent 1290 Infinity
Column Agilent ZORBAX Eclipse Plus C18 (100 x 2.1mm,1.8um) Agilent ZORBAX Eclipse Plus C18 (100 x 2.1mm,1.8um)
MS Type ESI ESI
MS instrument type QTOF QTOF
MS instrument name Agilent 6546 QTOF Agilent 6546 QTOF
Ion Mode POSITIVE NEGATIVE
Units Peak height Peak height

Chromatography:

Chromatography ID:CH005368
Instrument Name:Agilent 1290 Infinity
Column Name:Agilent ZORBAX Eclipse Plus C18 (100 x 2.1mm,1.8um)
Column Temperature:45
Flow Gradient:A stepped-linear 16 min gradient was applied at 0.4 mL/min as described: held at 50% B for 2.5 min, quickly increased to 57% B over 0.1 min, increased linearly to 70% B until reaching 9 min, increased quickly to 93% B for 0.1 min and then increased to 96% B for 1.1 min. At 11.1 min, the gradient was held at 100% B until 12 min, decreased to 15% B for 0.2 min, and then held there for 3.8 min.
Flow Rate:0.4 mL/min
Solvent A:50% water/30% acetonitrile/20% isopropanol; 10mM ammonium formate
Solvent B:1% water/9% acetonitrile/90% isopropanol; 10mM ammonium formate
Chromatography Type:Reversed phase

MS:

MS ID:MS006767
Analysis ID:AN007070
Instrument Name:Agilent 6546 QTOF
Instrument Type:QTOF
MS Type:ESI
MS Comments:At a scan rate of 3 spectra/sec, full scan data was acquired in the mass range 50-1700 m/z. In positive ionization mode, the following QTOF-MS parameters were used: a gas temperature of 200 degrees C, gas flow at 10 L/min, nebulizer at 50 psig, sheath gas temperature at 300 degrees C, sheath gas flow at 12 L/min, and capillary voltage at 3500 V.
Ion Mode:POSITIVE
  
MS ID:MS006768
Analysis ID:AN007071
Instrument Name:Agilent 6546 QTOF
Instrument Type:QTOF
MS Type:ESI
MS Comments:In negative ionization mode, all of the parameters were the same, except for the capillary voltage set to 3000 V.
Ion Mode:NEGATIVE
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