Summary of Study ST002836

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 PR001776. The data can be accessed directly via it's Project DOI: 10.21228/M84T59 This work is supported by NIH grant, U2C- DK119886.

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Study IDST002836
Study TitleBacterial tryptophan metabolites increased by prebiotic galactooligosaccharide reduce microglial reactivity and are associated with lower anxiety-like behavior (Intestine)
Study SummaryPrebiotic galactooligosaccharides (GOS) reduce anxiety-like behaviors in mice and humans. However, the biological pathways behind these behavioral changes are not well understood. To begin to study these pathways, C57BL/6 mice were fed a standard diet with or without GOS supplementation for 3 weeks prior to testing on the open field. After behavioral testing, colonic contents and serum were collected for bacteriome (16S rRNA gene sequencing, colonic contents only) and metabolome (UPLC-MS, colonic contents and serum data) analyses. As expected, GOS significantly reduced anxiety-like behavior (i.e., increased time in the center (p < 0.05)). Time in the center was significantly correlated with serum methyl-indole-3-acetate (mI3A). This metabolite, which is a methylated form of indole-3-acetate, is derived from bacterial metabolism of tryptophan. Sequencing analyses showed that GOS significantly increased Akkermansia, which is known to metabolize both GOS and tryptophan. To test the hypothesis that mI3A can reduce anxiety-like behavior and affect microglial activity, we first tested mI3A effects on LPS-stimulated BV2 microglia. Cells treated with mI3A produced significantly less CCL2 and TNF-α than vehicle-treated cells (p<.05). We then treated mice with an intraperitoneal injection of mI3A or vehicle control, and found that mice given mI3A had lower CCL2 in the prefrontal cortex and hippocampus, as well as a reduction in a composite behavioral score in the open field. Together, these data support a novel pathway through which GOS reduces anxiety-like behaviors in mice, and suggests that the bacterial metabolite mI3A, which is elevated by GOS, reduces microglial CCL2, which in turn reduces anxiety-like behavior.
Institute
National Center for Advancing Translational Sciences
Last NameSpencer
First NameKyle
Address9800 Medical Center Dr, Rockville, MD 20850
Emailkyle.spencer@nih.gov
Phone989-708-4858
Submit Date2023-08-21
Analysis Type DetailOther
Release Date2024-02-21
Release Version1
Kyle Spencer Kyle Spencer
https://dx.doi.org/10.21228/M84T59
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Factors:

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

mb_sample_id local_sample_id GROUP_ID
SA307260NACH-00290CON
SA307261NACH-00291CON
SA307262NACH-00293CON
SA307263NACH-00289CON
SA307264NACH-00292CON
SA307265NACH-00288CON
SA307266NACH-00284GOS
SA307267NACH-00283GOS
SA307268NACH-00285GOS
SA307269NACH-00286GOS
SA307270NACH-00287GOS
SA307271NACH-00282GOS
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