The Dose–Response Effect of Fluoride Exposure on the Gut Microbiome and Its Functional Pathways in Rats

Abstract

Metabolic activities within the gut microbiome are intimately linked to human health and disease, especially within the context of environmental exposure and its potential ramifications. Perturbations within this microbiome, termed “gut microbiome perturbations”, have emerged as plausible intermediaries in the onset or exacerbation of diseases following environmental chemical exposures, with fluoride being a compound of particular concern. Despite the well-documented adverse impacts of excessive fluoride on various human physiological systems—ranging from skeletal to neurological—the nuanced dynamics between fluoride exposure, the gut microbiome, and the resulting dose–response relationship remains a scientific enigma. Leveraging the precision of 16S rRNA high-throughput sequencing, this study meticulously examines the ramifications of diverse fluoride concentrations on the gut microbiome’s composition and functional capabilities within Wistar rats. Our findings indicate a profound shift in the intestinal microbial composition following fluoride exposure, marked by a dose-dependent modulation in the abundance of key genera, including Pelagibacterium, Bilophila, Turicibacter, and Roseburia. Moreover, discernible alterations were observed in critical functional and metabolic pathways of the microbiome, such as D-lyxose ketol-isomerase and DNA polymerase III subunit gamma/tau, underscoring the broad-reaching implications of fluoride exposure. Intriguingly, correlation analyses elucidated strong associations between specific bacterial co-abundance groups (CAGs) and these shifted metabolic pathways. In essence, fluoride exposure not only perturbs the compositional equilibrium of the gut microbiota but also instigates profound shifts in its metabolic landscape. These intricate alterations may provide a mechanistic foundation for understanding fluoride’s potential toxicological effects mediated via gut microbiome modulation.

Control of Dental Caries in Children and Adolescents Using Fluoride: An Overview of Community-Level Fluoridation Methods

“…The risk of developing fluorotic lesions of enamel due to the ingestion of recommended levels of fluoride during amelogenesis has been deemed acceptable when compared to the anticaries benefits of fluoride [ 53 , 64 ]. However, excessive fluoride intake can have negative effects on thyroid function, the skeletal system, the reproductive system, and cardiovascular health [ 65 , 66 , 67 ]. The risk of fluorosis depends on the dose, duration, and timing of fluoride exposure during tooth enamel formation [ 53 , 68 ].…”

Progress in research on the role of fluoride in immune damage

“…In addition, using high-throughput 16S rRNA gene sequencing technology, it has been found that fungi may be one of the important factors affecting intestinal function, and excessive fluorine can affect the species richness of intestinal fungi in mice, suggesting that fluorine may cause adverse intestinal symptoms by causing an imbalance in the intestinal fungal population, thus affecting the normal intestinal function ( 81 , 82 ). Moreover, fluoride exposure not only disturbed the compositional balance of the gut microbiome, but also triggered metabolic disorders ( 83 ). Alterations in intestinal microbiota and metabolome play a critical role in regulating disease susceptibility and multi-organ damage after excessive fluoride exposure ( 73 ).…”