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

Author:

Mo Zhe12ORCID,Wang Jian1,Meng Xinyue1,Li Ailin1,Li Zhe1,Que Wenjun1,Wang Tuo1,Tarnue Korto Fatti1,Ma Xu1,Liu Ying1,Yan Shirui1,Wu Lei1,Zhang Rui1,Pei Junrui1,Wang Xiaofeng2

Affiliation:

1. Key Laboratory of Etiology and Epidemiology, Chinese Center for Disease Control and Prevention, Center for Endemic Disease Control, Education Bureau of Heilongjiang Province & National Health Commission (23618504), Institute for Fluorosis Disease Control, Harbin Medical University, Harbin 150081, China

2. Department of Environmental Health, Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou 310051, China

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.

Funder

National Natural Science Foundation of China

Natural Science Foundation of Zhejiang Province, China

Opening Foundation of NHC Key Laboratory of Etiology and Epidemiology

Publisher

MDPI AG

Subject

Molecular Biology,Biochemistry,Endocrinology, Diabetes and Metabolism

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