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Intestinal changes associated with fluoride exposure in rats: Integrative morphological, proteomic and microbiome
Aline Dionizio1, Dawud Abduweli Uyghurturk2, Carina Guimarães Souza Melo1
1Department of Biological Sciences, Bauru School of Dentistry, University of São Paulo, Bauru, Brazil.
Chemosphere
|January 28, 2021
Summary
Subchronic fluoride (F) exposure alters rat ileum morphology, neuronal signaling, and gut microbiome composition. These changes suggest potential inflammation and gut dysfunction, warranting further investigation into fluoride
Area of Science:
- Toxicology
- Gastroenterology
- Microbiome Research
Background:
- Gastrointestinal issues are early indicators of fluoride toxicity.
- Subchronic, lower-level fluoride exposure's impact on the gut remains unclear.
- Investigating fluoride's effects on the ileum is crucial for understanding gut health.
Purpose of the Study:
- To assess the impact of subchronic fluoride exposure on rat ileum morphology, proteome, and microbiome.
- To evaluate dose-dependent effects of fluoride on gut physiology.
- To identify specific molecular and microbial changes induced by fluoride.
Main Methods:
- Male rats were exposed to 0, 10, or 50 mg F/L in drinking water for 30 days.
- Ileum tissues were analyzed for morphological changes, neuronal markers (HuC/D, CGRP, SP, VIP), and protein expression (proteomics).
- Gut microbiome composition was assessed using metagenomics.
Main Results:
- Fluoride exposure decreased HuC/D-IR neurons and increased CGRP-IR and SP-IR varicosities.
- Ileum wall thickness and tunica muscularis increased significantly at both fluoride doses.
- Proteomics revealed increased myosin isoforms and decreased Gastrotopin; microbiome analysis showed reduced Class Clostridia and Ureaplasma at specific doses.
Conclusions:
- Subchronic fluoride exposure induces significant morphological and proteomic changes in the rat ileum.
- Fluoride exposure alters gut microbiome composition, with dose-dependent effects.
- Observed alterations suggest a link between fluoride, inflammation, and gut microbiome dysbiosis.

