Abstract
Chronic exposure to excessive environmental fluoride has caused fluorosis to become a major public health problem worldwide. Although studies on stress pathways, signaling pathways, and apoptosis induced by fluoride have provided an in-depth understanding of the mechanism of this disease, its exact pathogenesis remains unclear. We hypothesized that the human gut microbiota and metabolome are associated with the pathogenesis of this disease. To get further insight into the profiles of intestinal microbiota and metabolome in coal-burning-induced endemic fluorosis patients, we conducted 16S rRNA sequencing of the intestinal microbial DNA and carried out non-targeted metabolomics of fecal samples from 32 patients with skeletal fluorosis and 33 matched healthy controls in Guizhou, China. We found that the gut microbiota of coal-burning endemic fluorosis patients displayed significant differences in composition, diversity, and abundance compared with healthy controls. This was characterized by an increase in the relative abundance of Verrucomicrobiota, Desulfobacterota, Nitrospirota, Crenarchaeota, Chloroflexi, Myxococcota, Acidobacteriota, Proteobacteria, and unidentified_Bacteria, and a significant decrease in the relative abundance of Firmicutes and Bacteroidetes at the phylum level. Additionally, at the genus level, the relative abundance of some beneficial bacteria, such as Bacteroides, Megamonas, Bifidobacterium, and Faecalibacterium, was significantly reduced. We also demonstrated that, at the genus level, some gut microbial markers, including Anaeromyxobacter, MND1, oc32, Haliangium, and Adurb.Bin063_1, showed potential for identifying coal-burning endemic fluorosis. Moreover, non-targeted metabolomics and correlation analysis revealed the changes in the metabolome, particularly the gut microbiota–derived tryptophan metabolites such as tryptamine, 5-hydroxyindoleacetic acid, and indoleacetaldehyde. Our results indicated that excessive fluoride might cause xenobiotic-mediated dysbiosis of human gut microbiota and metabolic disorders. These findings suggest that the alterations in gut microbiota and metabolome play vital roles in regulating disease susceptibility and multi-organ damage after excessive fluoride exposure.
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The datasets analyzed during the present study are available from the first author on reasonable request.
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Acknowledgements
We would like to thank Xingyu Liu and Dong Wang (Hospital of Shuguang Town, Nayong County, Bijie City, Guizhou Province, China) for their help with fecal sample collection. We also thank the generous volunteers who participated in this study. In addition, we would like to thank Editage (www.editage.cn) for English language editing.
Funding
This work was supported by the Science and Technology Foundation of Guizhou Province (grant no. QKHJ-ZK[2021]485, QKHJ-ZK[2023]560); the Science and Technology Project of Guizhou Provincial Department of Education (grant no. JZ-2021–9) and the Science and Technology Foundation of Zunyi (grant nos. ZSKH-HZ-[2020] 213 / 253); the National Natural Science Foundation of China (grant no. 81960747); the Project of Guizhou Administration of Traditional Chinese medicine (grant no. QZYY-2020–008); Science and Technology Innovation Leading Academics of National High-level Personnel of Special Support Program, PR China (grant no. GKFZ-2018–29); and Guizhou High-Level Innovative Talent Support Program, PR China (grant no. QKHPT-RC-GCC[2022]001–1).
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Jianbin Wang conceived, designed, and conducted the study; analyzed and interpreted the results; and drafted the manuscript. Chao Yu and Jiarong Zhang conducted this study. Ruming Liu analyzed and interpreted the results. Jianhui Xiao managed the project, analyzed and interpreted the results, and revised the manuscript.
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Wang, J., Yu, C., Zhang, J. et al. Aberrant gut microbiota and fecal metabolites in patients with coal-burning endemic fluorosis in Guizhou, China. Environ Sci Pollut Res 30, 69913–69926 (2023). https://doi.org/10.1007/s11356-023-27051-9
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DOI: https://doi.org/10.1007/s11356-023-27051-9