Summary of Study ST000885

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 PR000614. The data can be accessed directly via it's Project DOI: 10.21228/M8KD9Q This work is supported by NIH grant, U2C- DK119886.

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Study IDST000885
Study TitleGut Microbiota Modulate Brain Insulin Sensitivity and Neurobehavior
Study TypeMetabolite profiling of cecal contents and brains of mice under diet-induced obesity (DIO) with and without antibiotic treatments.
Study SummaryC57BL/6J mice were purchased from Jackson Laboratory and maintained on either a normal chow containing 22% of calories from fat, 23% from protein, and 55% from carbohydrates (Mouse diet 9F 5020; PharmaServ) or a high-fat diet (Open Source Diet, D12492; Research Diets) containing 60% of calories from fat, 20% from protein, and 20% from carbohydrates for 6 weeks. During the last 2 weeks, some of the HFD mice were treated with vancomycin or metronidazole (1 g/L in the drinking water). All mice were housed at 22°C on a 12 h light/dark cycle. All animal studies were approved by the IACUC of Joslin Diabetes Center (# 97-05) and Harvard Medical School (# 05131) and were in accordance with NIH guidelines. The metabolite profiling was conducted on plasma, hypothalamus and nucleus accumbens.
Institute
Broad Institute of MIT and Harvard
Last NameAvila-Pacheco
First NameJulian
Address415 Main Street
Emailjravilap@broadinstitute.org
Phone617-714-8264
Submit Date2017-10-30
Num Groups12
Total Subjects24
Raw Data AvailableYes
Raw Data File Type(s)d
Analysis Type DetailLC-MS
Release Date2017-10-30
Release Version1
Julian Avila-Pacheco Julian Avila-Pacheco
https://dx.doi.org/10.21228/M8KD9Q
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Project:

Project ID:PR000614
Project DOI:doi: 10.21228/M8KD9Q
Project Title:Gut Microbiota Modulate Brain Insulin Sensitivity and Neurobehavior
Project Type:Metabolite profiling of cecal contents and brains of mice under diet-induced obesity (DIO) with and without antibiotic treatments.
Project Summary:Obesity and diabetes in humans are associated with increased rates of anxiety and depression. To understand the role of the gut microbiome and brain insulin resistance in these disorders, we evaluated behaviors and insulin action in brain of mice with diet-induced obesity (DIO) with and without antibiotic treatment. We find that DIO mice have behaviors reflective of increased anxiety and depression. This is associated with decreased insulin signaling and increased inflammation in multiple brain regions. Treatment with oral metronidazole or vancomycin decreases inflammation, improves insulin signaling in the brain and reduces signs of anxiety and depression. These effects are transferable to germ-free mice by fecal transplant of gut microbiota and are associated with changes in the levels of tryptophan, GABA, BDNF, amino acids and multiple acylcarnitines in the brain. Thus, changes in gut microbiota can control brain insulin signaling and metabolite levels, and this leads to altered neurobehaviors.
Institute:Broad Institute of MIT and Harvard
Department:Metabolomics Platform
Last Name:Avila-Pacheco
First Name:Julian
Address:415 Main Street, Rm 7175, Cambridge, MA, 02142, USA
Email:jravilap@broadinstitute.org
Phone:6177148264
Contributors:Marion Soto, Clémence Herzog, Julian Avila-Pacheco, Shiho Fujisaka, Kevin Bullock, Clary B. Clish, and C. Ronald Kahn

Subject:

Subject ID:SU000919
Subject Type:Animal
Subject Species:Mus musculus
Taxonomy ID:10090

Factors:

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

mb_sample_id local_sample_id Diet Treatment Tissue
SA0513860002.dChow none hypothalamus
SA0513870004.dChow none hypothalamus
SA0513880014.dChow none hypothalamus
SA0513890022.dChow none hypothalamus
SA0513900015.dChow none hypothalamus
SA0513910010.dChow none hypothalamus
SA0513920039.dChow none nucleus accumbens
SA0513930034.dChow none nucleus accumbens
SA0513940026.dChow none nucleus accumbens
SA0513950046.dChow none nucleus accumbens
SA0513960028.dChow none nucleus accumbens
SA0513970038.dChow none nucleus accumbens
SA0513980050.dChow none plasma
SA0513990058.dChow none plasma
SA0514000063.dChow none plasma
SA0514010062.dChow none plasma
SA0514020052.dChow none plasma
SA0514030070.dChow none plasma
SA0514040008.dHFD metronidazole hypothalamus
SA0514050012.dHFD metronidazole hypothalamus
SA0514060006.dHFD metronidazole hypothalamus
SA0514070001.dHFD metronidazole hypothalamus
SA0514080018.dHFD metronidazole hypothalamus
SA0514090047.dHFD metronidazole nucleus accumbens
SA0514100036.dHFD metronidazole nucleus accumbens
SA0514110025.dHFD metronidazole nucleus accumbens
SA0514120042.dHFD metronidazole nucleus accumbens
SA0514130030.dHFD metronidazole nucleus accumbens
SA0514140032.dHFD metronidazole nucleus accumbens
SA0514150060.dHFD metronidazole plasma
SA0514160071.dHFD metronidazole plasma
SA0514170054.dHFD metronidazole plasma
SA0514180066.dHFD metronidazole plasma
SA0514190049.dHFD metronidazole plasma
SA0514200056.dHFD metronidazole plasma
SA0514210013.dHFD none hypothalamus
SA0514220021.dHFD none hypothalamus
SA0514230024.dHFD none hypothalamus
SA0514240020.dHFD none hypothalamus
SA0514250007.dHFD none hypothalamus
SA0514260011.dHFD none hypothalamus
SA0514270035.dHFD none nucleus accumbens
SA0514280037.dHFD none nucleus accumbens
SA0514290044.dHFD none nucleus accumbens
SA0514300031.dHFD none nucleus accumbens
SA0514310045.dHFD none nucleus accumbens
SA0514320048.dHFD none nucleus accumbens
SA0514330069.dHFD none plasma
SA0514340059.dHFD none plasma
SA0514350055.dHFD none plasma
SA0514360061.dHFD none plasma
SA0514370068.dHFD none plasma
SA0514380072.dHFD none plasma
SA0514390019.dHFD vancomycin hypothalamus
SA0514400005.dHFD vancomycin hypothalamus
SA0514410009.dHFD vancomycin hypothalamus
SA0514420016.dHFD vancomycin hypothalamus
SA0514430017.dHFD vancomycin hypothalamus
SA0514440003.dHFD vancomycin hypothalamus
SA0514450043.dHFD vancomycin nucleus accumbens
SA0514460040.dHFD vancomycin nucleus accumbens
SA0514470041.dHFD vancomycin nucleus accumbens
SA0514480029.dHFD vancomycin nucleus accumbens
SA0514490027.dHFD vancomycin nucleus accumbens
SA0514500033.dHFD vancomycin nucleus accumbens
SA0514510067.dHFD vancomycin plasma
SA0514520065.dHFD vancomycin plasma
SA0514530064.dHFD vancomycin plasma
SA0514540057.dHFD vancomycin plasma
SA0514550051.dHFD vancomycin plasma
SA0514560053.dHFD vancomycin plasma
Showing results 1 to 71 of 71

Collection:

Collection ID:CO000913
Collection Summary:The mice were fasted for 2 hours and anesthetized with isoflurane before collecting cecum and plasma.
Sample Type:Blood
Blood Serum Or Plasma:Plasma

Treatment:

Treatment ID:TR000933
Treatment Summary:6 weeks-old male C57BL/6J mice were purchased from Jackson Laboratory and maintained on either a normal chow containing 22% of calories from fat, 23% from protein, and 55% from carbohydrates (Mouse diet 9F 5020; PharmaServ) or a high-fat diet (Open Source Diet, D12492; Research Diets) containing 60% of calories from fat, 20% from protein, and 20% from carbohydrates for 6 weeks. During the last 2 weeks, some of the HFD mice were treated with vancomycin or metronidazole (1 g/L in the drinking water).

Sample Preparation:

Sampleprep ID:SP000926
Sampleprep Summary:Plasma: LC-MS samples were prepared from plasma (10 μL) via protein precipitation with the addition of nine volumes of 74.9:24.9:0.2 v/v/v acetonitrile/methanol/formic acid containing stable isotope-labeled internal standards (valine-d8, Isotec; and phenylalanine-d8, Cambridge Isotope Laboratories; Andover, MA). The samples are centrifuged (10 min, 9,000 x g, 4°C), and the supernatants were injected directly. Nucleus accumbens and Hypothalamus: Frozen brain tissue samples were homogenized in 4 volumes of HPLC water (J. T. Baker, Center Valley Pa.) using a TissueLyser II (Qiagen, Hilden, Germany) with 3mm tungsten beads at 20 Hz in two 2-minute cycles. Homogenates were then aliquoted for profiling. Samples were prepared from lysates(10 μL) via protein precipitation with the addition of nine volumes of 74.9:24.9:0.2 v/v/v acetonitrile/methanol/formic acid containing stable isotope-labeled internal standards (valine-d8, Isotec; and phenylalanine-d8, Cambridge Isotope Laboratories; Andover, MA). The samples are centrifuged (10 min, 9,000 x g, 4°C), and the supernatants were injected directly.

Combined analysis:

Analysis ID AN001442
Analysis type MS
Chromatography type HILIC
Chromatography system Agilent 1290 infinity II
Column Waters Atlantis HILIC (150 x 2mm)
MS Type ESI
MS instrument type Triple quadrupole
MS instrument name Agilent 6495 QQQ
Ion Mode POSITIVE
Units Peak area

Chromatography:

Chromatography ID:CH001013
Chromatography Summary:A 150 x 2.1 mm Atlantis HILIC column (Waters) was eluted isocratically at a flow rate of 250 µL/min with 5% mobile phase A (10 mM ammonium formate and 0.1% formic acid in water) for 1 minute followed by a linear gradient to 40% mobile phase B (acetonitrile with 0.1% formic acid) over 10 minutes
Instrument Name:Agilent 1290 infinity II
Column Name:Waters Atlantis HILIC (150 x 2mm)
Solvent A:100% water; 0.1% formic acid; 10 mM ammonium formate
Solvent B:100% acetonitrile; 0.1% formic acid
Chromatography Type:HILIC

MS:

MS ID:MS001332
Analysis ID:AN001442
Instrument Name:Agilent 6495 QQQ
Instrument Type:Triple quadrupole
MS Type:ESI
Ion Mode:POSITIVE
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