Institute of Medicinal Biotechnology, Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Huichuan District, Zunyi, 563003, China.
Zunyi Municipal Key Laboratory of Medicinal Biotechnology & Guizhou Provincial Research Center for Translational Medicine, Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Huichuan District, Zunyi, 563003, China.
Environ Sci Pollut Res Int. 2023 Jun;30(27):69913-69926. doi: 10.1007/s11356-023-27051-9. Epub 2023 May 4.
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.
慢性暴露于过量的环境氟化物已使氟中毒成为全球主要的公共卫生问题。虽然关于氟化物诱导的应激途径、信号通路和细胞凋亡的研究为深入了解该疾病的发病机制提供了依据，但氟中毒的确切发病机制仍不清楚。我们假设人类肠道微生物群和代谢组与这种疾病的发病机制有关。为了更深入地了解燃煤型地方性氟中毒患者肠道微生物群和代谢组的特征，我们对来自中国贵州的 32 名氟骨症患者和 33 名匹配的健康对照者的肠道微生物 DNA 进行了 16S rRNA 测序，并对粪便样本进行了非靶向代谢组学分析。我们发现，燃煤型地方性氟中毒患者的肠道微生物群在组成、多样性和丰度上与健康对照组相比存在显著差异。这表现为厚壁菌门和拟杆菌门的相对丰度显著降低，疣微菌门、脱硫杆菌门、硝化螺旋菌门、泉古菌门、绿弯菌门、黏胶球形菌门、酸杆菌门、变形菌门和未鉴定的_Bacteria 的相对丰度增加。此外，在属水平上，一些有益细菌如拟杆菌属、巨单胞菌属、双歧杆菌属和粪杆菌属的相对丰度显著降低。我们还证明，在属水平上，一些肠道微生物标志物，包括厌氧棒状杆菌属、MND1、oc32、盐单胞菌属和 Adurb.Bin063_1，具有识别燃煤型地方性氟中毒的潜力。此外，非靶向代谢组学和相关性分析揭示了代谢组的变化，特别是肠道微生物衍生的色氨酸代谢物如色胺、5-羟基吲哚乙酸和吲哚乙醛的变化。我们的结果表明，过量的氟化物可能导致人类肠道微生物群的外源性物质介导的失调和代谢紊乱。这些发现表明，肠道微生物群和代谢组的改变在调节过量氟暴露后疾病易感性和多器官损伤方面发挥着重要作用。
