Summary of Study ST000885

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench,, 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.
Broad Institute of MIT and Harvard
Last NameAvila-Pacheco
First NameJulian
Address415 Main Street
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 application/zip

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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
Contributors:Marion Soto, Clémence Herzog, Julian Avila-Pacheco, Shiho Fujisaka, Kevin Bullock, Clary B. Clish, and C. Ronald Kahn