Summary of Study ST004196
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 PR002645. The data can be accessed directly via it's Project DOI: 10.21228/M8RN9P 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.
| Study ID | ST004196 |
| Study Title | High fluoride exposure disrupts the intestinal microbiota and induces intestinal barrier damage |
| Study Summary | Our study establishes an acute high-fluoride exposure model by gavaging 3-week-old C57BL/6J mice with 0 (control, C), 12 (low fluoride, FL), or 24 mg/kg (high fluoride, FH) sodium fluoride (NaF) for 8 weeks (n=10 per group), with standardized housing conditions (22±2℃, 12 h light/dark cycle). After euthanasia, ileal tissues, ileal contents, and serum were collected for histological, molecular, metagenomic, and non-targeted metabolomic analyses. Histological and biochemical results showed that high fluoride (FH group) increased ileal crypt depth, elevated serum intestinal permeability indicators (LPS, DAO, D-LA), and reduced ileal antioxidant capacity (decreased T-AOC, GSH, SOD; increased H₂O₂). Immunofluorescence, Western blotting, and transmission electron microscopy revealed that high fluoride activated the RhoA/ROCK pathway (upregulated RhoA, ROCK1/2, p-MLC), induced abnormal rearrangement and aggregation of F-actin (P<0.001 vs C), and disrupted the apical junctional complex (AJC)—manifested by downregulated expression and cytoplasmic translocation of ZO-1, Claudin-1, and β-catenin. Metagenomic analysis of ileal contents indicated high fluoride-induced gut microbiota dysbiosis, with reduced abundance of Akkermansia muciniphila and enrichment of Lactobacillus johnsonii; two key species (Bifidobacterium sp. SO1 and Schaalia turicensis) were screened, showing strong correlations with intestinal barrier phenotypes, RhoA/ROCK pathway molecules, and cytoskeleton-related metabolites. Non-targeted metabolomics identified 620 differential metabolites, with 11 linked to cytoskeleton function; high fluoride enriched linoleic acid metabolism (upregulated 9-HODE, 13-KODE; P<0.05 vs C) and sphingolipid metabolism (downregulated sphingosine) pathways. These findings confirm that high fluoride impairs the mouse intestinal barrier via the gut microbiota-mediated "RhoA/ROCK-cytoskeleton remodeling" axis, providing novel insights into fluoride-induced intestinal toxicity mechanisms and a basis for preventing fluoride-related intestinal diseases. |
| Institute | Animal Microecology Institute, Sichuan Agricultural University |
| Department | College Of Veterinary Medicine |
| Laboratory | Animal Microecology Institute, Sichuan Agricultural University |
| Last Name | DanDan |
| First Name | Wang |
| Address | Huimin Road, Wenjiang District, Chengdu, Sichuan, 611100, China |
| 1150784177@qq.com | |
| Phone | 17656691293 |
| Submit Date | 2025-09-14 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | mzML, raw(Thermo) |
| Analysis Type Detail | LC-MS |
| Release Date | 2025-10-08 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Project:
| Project ID: | PR002645 |
| Project DOI: | doi: 10.21228/M8RN9P |
| Project Title: | High Fluoride Exposure Disrupts Gut Microbiota and Induces Intestinal Barrier Damage via RhoA/ROCK-Mediated Cytoskeletal Remodeling |
| Project Summary: | Fluoride is an environmental pollutant that causes intestinal barrier damage, but the role of the "gut microbiota-RhoA/ROCK-cytoskeleton" axis in this process remains unclear. The aim of this project is to investigate the damage mechanism of high fluoride exposure on the intestinal barrier in mice. Focusing on the core objective of how high fluoride affects the intestinal barrier through the gut microbiota-mediated "RhoA/ROCK - cytoskeleton remodeling" axis, the study combines metagenomic approaches and leverages untargeted metabolomic analysis to reveal the gut microbiota dysbiosis and significant changes in intestinal metabolites induced by high fluoride. It clarifies the variation of cytoskeleton-related differential metabolites and screens out the key bacterial species that are strongly associated with the phenotypic characteristics of intestinal barrier damage, cytoskeletal core proteins, key tight junction proteins, and RhoA/ROCK pathway molecules in mice. In doing so, this research provides a new perspective for studying the mechanism of fluoride-induced intestinal barrier damage and lays a foundation for the prevention of fluoride-related intestinal diseases. |
| Institute: | Sichuan Agricultural University |
| Department: | College Of Veterinary Medicine |
| Laboratory: | Animal Microecology Institute, Sichuan Agricultural University |
| Last Name: | DanDan |
| First Name: | Wang |
| Address: | Huimin Road, Wenjiang District, Chengdu, Sichuan, 611100, China |
| Email: | 1150784177@qq.com |
| Phone: | 17656691293 |
Subject:
| Subject ID: | SU004348 |
| Subject Type: | Mammal |
| Subject Species: | Mus musculus |
| Taxonomy ID: | 10090 |
Factors:
Subject type: Mammal; Subject species: Mus musculus (Factor headings shown in green)
| mb_sample_id | local_sample_id | experimental factor(s) | Sample source |
|---|---|---|---|
| SA483706 | FH-6 | gavage with high-concentration sodium fluoride | mouse ileum |
| SA483707 | FH-5 | gavage with high-concentration sodium fluoride | mouse ileum |
| SA483708 | FH-4 | gavage with high-concentration sodium fluoride | mouse ileum |
| SA483709 | FH-3 | gavage with high-concentration sodium fluoride | mouse ileum |
| SA483710 | FH-2 | gavage with high-concentration sodium fluoride | mouse ileum |
| SA483711 | FH-1 | gavage with high-concentration sodium fluoride | mouse ileum |
| SA483712 | FL-5 | gavage with low-concentration sodium fluoride | mouse ileum |
| SA483713 | FL-6 | gavage with low-concentration sodium fluoride | mouse ileum |
| SA483714 | FL-4 | gavage with low-concentration sodium fluoride | mouse ileum |
| SA483715 | FL-3 | gavage with low-concentration sodium fluoride | mouse ileum |
| SA483716 | FL-2 | gavage with low-concentration sodium fluoride | mouse ileum |
| SA483717 | FL-1 | gavage with low-concentration sodium fluoride | mouse ileum |
| SA483718 | C-2 | gavage with normal saline | mouse ileum |
| SA483719 | C-6 | gavage with normal saline | mouse ileum |
| SA483720 | C-5 | gavage with normal saline | mouse ileum |
| SA483721 | C-4 | gavage with normal saline | mouse ileum |
| SA483722 | C-3 | gavage with normal saline | mouse ileum |
| SA483723 | C-1 | gavage with normal saline | mouse ileum |
| Showing results 1 to 18 of 18 |
Collection:
| Collection ID: | CO004341 |
| Collection Summary: | After the mice are euthanized, the intestinal tissues are immediately removed. The ileal segments are separated, cut longitudinally to collect the contents of the mouse ileum. The samples are stored in a -80℃ refrigerator. |
| Sample Type: | Ileum |
Treatment:
| Treatment ID: | TR004357 |
| Treatment Summary: | The control group (C) was given 0.2 ml of normal saline by gavage; the low-concentration sodium fluoride group (FL) was given an equal volume of 12 mg/kg sodium fluoride solution by gavage; and the high-concentration sodium fluoride group (FH) was given an equal volume of 24 mg/kg sodium fluoride solution by gavage. |
Sample Preparation:
| Sampleprep ID: | SP004354 |
| Sampleprep Summary: | After collecting the mouse ileal contents, they were stored at -80°C. Subsequently, the methanol-water extraction method was adopted: using different proportions of methanol and water (e.g., 80% methanol aqueous solution), the mouse ileal content samples were subjected to operations such as vortex oscillation and ultrasonic treatment at low temperature to promote the release of polar and moderately polar metabolites in the samples into the extract. Methanol can precipitate proteins, avoiding protein interference with subsequent metabolite analysis, and effectively extract various polar metabolites such as amino acids, organic acids, and carbohydrates. The composition of metabolites was analyzed, and a comprehensive analysis was performed. |
Chromatography:
| Chromatography ID: | CH005294 |
| Instrument Name: | Thermo Vanquish |
| Column Name: | Waters ACQUITY UPLC HSS T3 (100 x 2.1 mm, 1.8 μm) |
| Column Temperature: | 40℃ |
| Flow Gradient: | 0-1 min:5%B; 1-4.7 min:5%-95%B; 4.7-6 min:95%B; 6-6.1 min:95%-5%B; 6.1-8.5 min:5%B. |
| Flow Rate: | 0.4 mL/min |
| Solvent A: | 100% Water; 0.1% Formic acid |
| Solvent B: | 100% Acetonitrile; 0.1% Formic acid |
| Chromatography Type: | Normal phase |
Analysis:
| Analysis ID: | AN006973 |
| Analysis Type: | MS |
| Chromatography ID: | CH005294 |
| Has Mz: | 1 |
| Has Rt: | 1 |
| Rt Units: | Minutes |
| Results File: | ST004196_AN006973_Results.txt |
| Units: | peak area |
| Analysis ID: | AN006974 |
| Analysis Type: | MS |
| Chromatography ID: | CH005294 |
| Has Mz: | 1 |
| Has Rt: | 1 |
| Rt Units: | Minutes |
| Results File: | ST004196_AN006974_Results.txt |
| Units: | peak area |
