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Identifying Serum Metabolites and Gut Bacterial Species Associated with Nephrotoxicity Caused by Arsenic and Fluoride Exposure

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Abstract

Co-contamination of arsenic (As) and fluoride (F) is widely distributed in groundwater, which are known risk factors for the nephrotoxicity. Emerging evidence has linked environmentally associated nephrotoxicity with the disturbance of gut microbiota and blood metabolites. In this study, we generated gut microbiota and blood metabolomic profile and identified multiple serum metabolites and gut bacteria species, which were associated with kidney injury on rat model exposed to As and F alone or combined. Combined As and F exposure significantly increased creatinine level. Abnormal autophagosomes and lysosome were observed, and the autophagic genes were enhanced in kidney tissue after single and combined As and F exposure. The metabolome data showed that single and combined As and F exposure remarkably altered the serum metabolites associated with the proximal tubule reabsorption function pathway, with glutamine and alpha-ketoglutarate level decreased in all exposed group. Furthermore, phosphatidylethanolamine (PE), the key contributor of autophagosomes, was decreased significantly in As and F + As exposed groups during the screen of autophagy-animal pathway. Multiple altered gut bacterial microbiota at phylum and species levels post As and F exposure were associated with targeted kidney injury, including p_Bacteroidetes, s_Chromohalobacter_unclassified, s_Halomonas_unclassified, s_Ignatzschineria_unclassified, s_Bacillus_subtilis, and s_Brevundimonas_sp._NA6. Meanwhile, our analysis indicated that As and F co-exposure possessed an interactive influence on gut microbiota. In conclusion, single or combined As and F exposure leads to the disruption of serum metabolic and gut microbiota profiles. Multiple metabolites and bacterial species are identified and associated with nephrotoxicity, which have potential to be developed as biomarkers of As and/or F-induced kidney damage.

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Data Availability

Data available on request from the authors. The data that support the findings of this study are available from the corresponding author, [niuruiyan2000@163.com], upon reasonable request.

Abbreviations

As:

Arsenic

F:

Fluoride

PE:

Phosphatidylethanolamine

TEM:

Transmission electron microscopy

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Funding

This work was supported by the National Natural Science Foundation of China (82173644) and the Shanxi Graduate Education Innovation Program (2020BY051).

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Authors and Affiliations

  1. College of Veterinary Medicine, Shanxi Agricultural University, Taigu, Shanxi, 030801, People’s Republic of China

    Xiaolin Tian, Zilong Sun & Ruiyan Niu

  2. School of Public Health, Shanxi Medical University, Taiyuan, Shanxi, 030001, People’s Republic of China

    Xiaolin Tian, Xiaoyan Yan & Penghui Liu

  3. Department of Epidemiology and Environmental Health, School of Public Health and Health Professions, University at Buffalo, Buffalo, NY, 14214, USA

    Xushen Chen

  4. School of Public Health, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, People’s Republic of China

    Xushen Chen

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Xiaolin Tian: Writing-original draft, writing-review and editing, conceptualization, formal analysis, data curation. Xiaoyan Yan: conceptualization, supervision, project administration, funding acquisition. Xushen Chen: data curation. Penghui Liu: validation, formal analysis. Zilong Sun: conceptualization, supervision. Ruiyan Niu: writing-review and editing, conceptualization, supervision.

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Tian, X., Yan, X., Chen, X. et al. Identifying Serum Metabolites and Gut Bacterial Species Associated with Nephrotoxicity Caused by Arsenic and Fluoride Exposure. Biol Trace Elem Res 201, 4870–4881 (2023). https://doi.org/10.1007/s12011-023-03568-5

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