Combined effects of lead and manganese on locomotor activity and microbiota in zebrafish

Yuan Xia; Chunyu Wang; Xiaoshun Zhang; Junyi Li; Ziyi Li; Jiawei Zhu; Qin Zhou; Jian Yang; Qingsong Chen; Xiaojing Meng

doi:10.1016/j.ecoenv.2023.115260

Combined effects of lead and manganese on locomotor activity and microbiota in zebrafish

Ecotoxicol Environ Saf. 2023 Sep 15:263:115260. doi: 10.1016/j.ecoenv.2023.115260. Epub 2023 Jul 22.

Authors

Yuan Xia¹, Chunyu Wang¹, Xiaoshun Zhang², Junyi Li¹, Ziyi Li¹, Jiawei Zhu³, Qin Zhou², Jian Yang¹, Qingsong Chen⁴, Xiaojing Meng⁵

Affiliations

¹ School of Public Health, Guangdong Pharmaceutical University, Guangzhou, Guangdong, China.
² Department of Occupational Health and Occupational Medicine, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, Guangdong, China.
³ Institute of Occupational Health Assessment, Guangdong Province Hospital for Occupational Disease Prevention and Treatment, Guangzhou, Guangdong, China.
⁴ School of Public Health, Guangdong Pharmaceutical University, Guangzhou, Guangdong, China. Electronic address: qingsongchen@aliyun.com.
⁵ Department of Occupational Health and Occupational Medicine, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, Guangdong, China. Electronic address: xiaojingmeng@smu.edu.cn.

PMID: 37487434
DOI: 10.1016/j.ecoenv.2023.115260

Abstract

Exposure to lead (Pb) and manganese (Mn) during early life influences neurodevelopment and increases the risk of neurodegenerative disorders. However, the level of developmental neurotoxicity due to combined exposure to the two metals remains unclear. Although the microbiota plays an essential part in the development of the nervous system via the gut-brain axis, there is a paucity of information regarding the interactions between exposure to Pb and Mn, the destruction of the microbiome, and neurodevelopmental impacts. To fill in this knowledge gap, we investigated the developmental neurotoxicity and effects on the microbiota of Pb (0.05 mg·L^-1) alone and in combination with Mn (0.3 mg·L^-1) in zebrafish larvae. Our results revealed that combined exposure precipitated higher malformation rates and lower locomotor activity levels than exposure to either Pb or Mn alone. Additionally, when we separated the combined exposure group from the other groups by applying unsupervised principal coordinates analysis (PCoA) and linear discriminant analysis (LEfSe) of microflora sequencing results, we observed extensive alterations in microbial abundances under combined-exposure conditions. Functional prediction analysis showed that combined exposure contributed to altered amino acid and lipid metabolism, and also that combined exposure to Pb and Mn reflected the greatest number of differentially activated biological pathways compared to the other three groups. ATP-binding cassette G (ABCG) genes and genes related to serotonin signaling and metabolism were altered following combined Pb and Mn exposure and exhibited disparate trends vis-à-vis Pb or Mn exposure alone. According to the results, the combined exposure to Pb and Mn led to more severe effects on both zebrafish locomotor activity and gut microbial composition. We suggest that the microbiota contributes to the combined neurotoxicity by increasing ABCG5 and ABCG8 gene expression.

Keywords: Concurrent exposure; Lead; Locomotor; Manganese; Microbiota; Toxicity; Zebrafish.

MeSH terms

Animals
Lead* / metabolism
Lead* / toxicity
Locomotion
Manganese / metabolism
Manganese / toxicity
Microbiota*
Zebrafish / metabolism

Substances

Lead
Manganese