Summary of Study ST002723

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 PR001689. The data can be accessed directly via it's Project DOI: 10.21228/M8CT6V 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 IDST002723
Study TitleINFLAMMATORY STIMULUS IN HUMANIZED MOUSE MODELS REVEALS THE ANTIOXIDANT EFFECTS OF ARONIA SUPPLEMENTATION
Study SummaryThe goal of this project is to elucidate interactions among the gut microbiome, anti-inflammatory food metabolomic signatures, and human inflammation phenotypes. Inflammation plays both direct and indirect roles in the development of type 2 diabetes (T2D), atherogenic cardiovascular diseases, and other causes of morbidity and mortality. In preliminary USDA-NIFA funded studies, we found that individuals of distinct low and high inflammation phenotypes have distinct metabolomic signatures in their blood. Anthocyanins and fiber of bioactive components of foods that have been shown to lower inflammation. However, there is tremendous inter-individual variability in bioavailability of anthocyanins and production of phenolic and aromatic metabolites in the colon that depends, at least in part, on digestive metabolism by microorganisms (the microbiota) in the gut. Fiber which acts as a prebiotic to enrich favorable gut microbes and as a fermentation substrate to produce favorable or unfavorable metabolites according to the unique makeup of the gut microbiota. However, little is known about the complex interactions among the gut microbiome, anti-inflammatory food metabolomic signatures, and human inflammation phenotypes. We propose a of human mechanistic clinical trials and mice humanized with fecal microbiome transplants to disentangle these complex interactions. To determine the metabolomic signatures anti-inflammatory foods and key bioactive components and determine associations with constituents of the gut microbiome (Aim 1A), we will measure in a human cohort the makeup of the gut microbiome and metabolomic changes induced by acute (3 d) ingestion of 1) chokeberry and chokeberry anthocyanins (n=75), and 2) lentils and lentil fiber (n=75). To determine whether these foods are related to the metabolomic signatures of low versus high inflammation phenotypes (Aim 1B), we will compare the metabolites and associated metabolic pathways of chokeberry, chokeberry anthocyanins, lentils, and lentil fiber to those associated with low and high inflammation phenotypes. To determine the impact of inter-individual variability of the gut microbiome on metabolomic signatures (Aim 2A), we will humanize mice with a diverse collection of human gut microbiomes and determine whether the makeup of the microbiome predicts features (metabolites) of chokeberry/anthocyanin, lentils/fiber metabolomic signatures. Findings from these experiments directly address the PAR-18-727 program area priority of “identification and validation of food and nutrient specific metabolic signatures that correlate with nutrient quality and efficacy and provide insights to develop synergistic food prebiotic based therapies to convert humans from high to low inflammation phenotypes to reduce disease risk and severity.
Institute
Montana State University
Last NamePeach
First NameJesse
AddressPO Box 173400, Bozeman, MT 59717
Emailjessepeach@gmail.com
Phone406-595-3100
Submit Date2023-05-28
Raw Data AvailableYes
Raw Data File Type(s)d
Analysis Type DetailLC-MS
Release Date2023-06-26
Release Version1
Jesse Peach Jesse Peach
https://dx.doi.org/10.21228/M8CT6V
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

Select appropriate tab below to view additional metadata details:

Project:

Project ID:PR001689
Project DOI:doi: 10.21228/M8CT6V
Project Title:A systems-level approach for disentangling complex interactions among the gut microbiome, anti-inflammatory food metabolomic signatures, and human inflammation phenotypes
Project Summary:The goal of this project is to elucidate interactions among the gut microbiome, anti-inflammatory food metabolomic signatures, and human inflammation phenotypes. Inflammation plays both direct and indirect roles in the development of type 2 diabetes (T2D), atherogenic cardiovascular diseases, and other causes of morbidity and mortality. In preliminary USDA-NIFA funded studies, we found that individuals of distinct low and high inflammation phenotypes have distinct metabolomic signatures in their blood. Anthocyanins and fiber of bioactive components of foods that have been shown to lower inflammation. However, there is tremendous inter-individual variability in bioavailability of anthocyanins and production of phenolic and aromatic metabolites in the colon that depends, at least in part, on digestive metabolism by microorganisms (the microbiota) in the gut. Fiber which acts as a prebiotic to enrich favorable gut microbes and as a fermentation substrate to produce favorable or unfavorable metabolites according to the unique makeup of the gut microbiota. However, little is known about the complex interactions among the gut microbiome, anti-inflammatory food metabolomic signatures, and human inflammation phenotypes. We propose a of human mechanistic clinical trials and mice humanized with fecal microbiome transplants to disentangle these complex interactions. To determine the metabolomic signatures anti-inflammatory foods and key bioactive components and determine associations with constituents of the gut microbiome (Aim 1A), we will measure in a human cohort the makeup of the gut microbiome and metabolomic changes induced by acute (3 d) ingestion of 1) chokeberry and chokeberry anthocyanins (n=75), and 2) lentils and lentil fiber (n=75). To determine whether these foods are related to the metabolomic signatures of low versus high inflammation phenotypes (Aim 1B), we will compare the metabolites and associated metabolic pathways of chokeberry, chokeberry anthocyanins, lentils, and lentil fiber to those associated with low and high inflammation phenotypes. To determine the impact of inter-individual variability of the gut microbiome on metabolomic signatures (Aim 2A), we will humanize mice with a diverse collection of human gut microbiomes and determine whether the makeup of the microbiome predicts features (metabolites) of chokeberry/anthocyanin, lentils/fiber metabolomic signatures. Findings from these experiments directly address the PAR-18-727 program area priority of “identification and validation of food and nutrient specific metabolic signatures that correlate with nutrient quality and efficacy and provide insights to develop synergistic food prebiotic based therapies to convert humans from high to low inflammation phenotypes to reduce disease risk and severity.
Institute:Montana State University
Last Name:Jesse
First Name:Peach
Address:PO Box 173400, Bozeman, MT 59717
Email:jessepeach@gmail.com
Phone:406-595-3100

Subject:

Subject ID:SU002829
Subject Type:Mammal
Subject Species:Mus musculus
Taxonomy ID:10090
Species Group:Mammals

Factors:

Subject type: Mammal; Subject species: Mus musculus (Factor headings shown in green)

mb_sample_id local_sample_id Donor Treatment Time
SA27386011 Aronia 0
SA27386161 Aronia 0
SA273862111 Aronia 0
SA27386371 Aronia 2
SA273864121 Aronia 2
SA27386521 Aronia 2
SA27386681 Aronia 4
SA27386731 Aronia 4
SA273868131 Aronia 4
SA273869141 Aronia 6
SA27387041 Aronia 6
SA27387191 Aronia 6
SA27387251 Aronia 8
SA273873101 Aronia 8
SA273874151 Aronia 8
SA273875211 Control 0
SA273876161 Control 0
SA273877261 Control 0
SA273878221 Control 2
SA273879171 Control 2
SA273880271 Control 2
SA273881231 Control 4
SA273882181 Control 4
SA273883281 Control 4
SA273884291 Control 6
SA273885241 Control 6
SA273886191 Control 6
SA273887201 Control 8
SA273888251 Control 8
SA273889301 Control 8
SA273890467 Aronia 0
SA273891417 Aronia 0
SA273892317 Aronia 0
SA273893687 Aronia 0
SA273894367 Aronia 0
SA273895477 Aronia 2
SA273896327 Aronia 2
SA273897427 Aronia 2
SA273898377 Aronia 2
SA273899337 Aronia 4
SA273900437 Aronia 4
SA273901487 Aronia 4
SA273902387 Aronia 4
SA273903347 Aronia 6
SA273904397 Aronia 6
SA273905497 Aronia 6
SA273906447 Aronia 6
SA273907407 Aronia 8
SA273908507 Aronia 8
SA273909357 Aronia 8
SA273910457 Aronia 8
SA273911517 Control 0
SA273912567 Control 0
SA273913617 Control 0
SA273914577 Control 2
SA273915627 Control 2
SA273916527 Control 2
SA273917537 Control 4
SA273918637 Control 4
SA273919587 Control 4
SA273920547 Control 6
SA273921597 Control 6
SA273922647 Control 6
SA273923557 Control 8
SA273924657 Control 8
SA273925607 Control 8
SA273926BlankBlank Blank Blank
SA27392767Extraction Blank Extraction Blank Extraction Blank
SA27392866Extraction Blank Extraction Blank Extraction Blank
Showing results 1 to 69 of 69

Collection:

Collection ID:CO002822
Collection Summary:Two human stool donors were selected based on their inflammation profile which occurred prior to gut microbial community profiling. Female germ- free (GF) C57BL/6J mice, originally purchased from the Jackson Laboratory (Bar Harbor, ME) were housed and bred at the American Association for the Accreditation of Laboratory Animal Care-accredited Animal Resource Center at Montana State University. Mice were held in individually ventilated cages with sterile bedding before and after fecal transplantation from selected human stool donors. Two female mice received an inoculation with fecal material from a human donor categorized as having low or high systemic inflammation based on serum levels of six proinflammatory cytokines. Human donor stool slurry aliquots were administered to GF mice through oral gavage. Sexually mature male GF C57BL/6J mice were added to each cage approximately one week after transplantation. Male mice removed prior to birth of pups. Pups from the inoculated dams were co-housed by sex (3 – 5 mice/cage) with different microbial inoculations placed in separate isolators. Mice from each microbial inoculation were assigned to one of two juice groups: Aronia (ARO LO , = 3, ARO HI , n=5), or a sugar-matched juice (CON LO ,n=3, CON HI , n = 3). Weekly measurements of body weight and food and fluid intake were recorded. Blood samples were collected at the same interval into serum separating tubes. Whole blood was allowed to clot for 15 minutes before centrifugation at 1200 RPM for 15 minutes with resulting serum aliquoted and stored at -80ºC until analysis. After T8 sample collection, mice were euthanized via rapid CO 2 asphyxiation.
Sample Type:Blood (serum)

Treatment:

Treatment ID:TR002838
Treatment Summary:At baseline (T0), regular drinking water was replaced with ARO or CON juice to begin a two-week familiarization period with the juice. ARO mice received an unpasteurized blend of Aronia juice, and CON mice received a sugar-matched beverage containing water, sorbitol, glucose, and fructose. The mice were housed in cages with free access to their respective juice. During the familiarization period, all mice received standard chow (LabDiet 5013).  After the 2-week familiarization period (T2), mice began a 6-week high-fat diet, delivered ad libitum concomitant with juice consumption. The HFD (Teklad TD.96132) was chosen to induce obesity and present an inflammatory stimulus (Duan et al., 2018) . The HFD mimics a Western style diet and consisted of 40.6% fat, 40.7% carbohydrate, and 18.7% protein and was particularly rich in sugars and trans-fatty acids. All chow provided was sterilized via autoclaving or irradiation. A total of 150 mL of juice was provided per cage each week. Juice was refilled three times each week.  

Sample Preparation:

Sampleprep ID:SP002835
Sampleprep Summary:Samples were stored at -80 deg. C until ready for analysis. A liquid extraction was completed with a protein precipitation. Samples were then concentrated and stored dry until LCMS analysis.

Combined analysis:

Analysis ID AN004414
Analysis type MS
Chromatography type HILIC
Chromatography system Agilent 1290 Infinity II
Column Waters ACQUITY UPLC BEH HILIC (150 x 2.1mm,1.7um)
MS Type ESI
MS instrument type QTOF
MS instrument name Agilent 6530 QTOF
Ion Mode POSITIVE
Units area

Chromatography:

Chromatography ID:CH003313
Instrument Name:Agilent 1290 Infinity II
Column Name:Waters ACQUITY UPLC BEH HILIC (150 x 2.1mm,1.7um)
Column Temperature:40
Flow Gradient:Linear 45-70%A
Flow Rate:0.4mL/min
Solvent A:Water with 0.1% formic acid
Solvent B:Acetonitrile with 0.1% formic acid
Chromatography Type:HILIC

MS:

MS ID:MS004161
Analysis ID:AN004414
Instrument Name:Agilent 6530 QTOF
Instrument Type:QTOF
MS Type:ESI
MS Comments:Mass Hunter to acquire data. Processed with msconvert and mzMine. Annotation with SIRIUS software.
Ion Mode:POSITIVE
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