Summary of project PR001776
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.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Project ID: | PR001776 |
| Project DOI: | doi: 10.21228/M84T59 |
| Project Title: | Bacterial tryptophan metabolites increased by prebiotic galactooligosaccharide reduce microglial reactivity and are associated with lower anxiety-like behavior |
| Project Summary: | Prebiotic 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-? 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 Name: | Spencer |
| First Name: | Kyle |
| Address: | 9800 Medical Center Dr, Rockville, MD 20850 |
| Email: | kyle.spencer@nih.gov |
| Phone: | 989-708-4858 |
Summary of all studies in project PR001776
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST002836 | Bacterial tryptophan metabolites increased by prebiotic galactooligosaccharide reduce microglial reactivity and are associated with lower anxiety-like behavior (Intestine) | Mus musculus | National Center for Advancing Translational Sciences | MS | 2024-02-21 | 1 | 12 | Not available |
| ST002837 | Bacterial tryptophan metabolites increased by prebiotic galactooligosaccharide reduce microglial reactivity and are associated with lower anxiety-like behavior (Blood) | Mus musculus | National Center for Advancing Translational Sciences | MS | 2024-02-21 | 1 | 11 | Not available |
