Effects of exposure to the neonicotinoid pesticide clothianidin on mouse intestinal microbiota under unpredictable environmental stress

Sakura Yonoichi; Tetsushi Hirano; Yukako Hara; Yuya Ishida; Asuka Shoda; Mako Kimura; Midori Murata; Youhei Mantani; Toshifumi Yokoyama; Yoshinori Ikenaka; Nobuhiko Hoshi

doi:10.1016/j.taap.2023.116795

Effects of exposure to the neonicotinoid pesticide clothianidin on mouse intestinal microbiota under unpredictable environmental stress

Toxicol Appl Pharmacol. 2024 Jan:482:116795. doi: 10.1016/j.taap.2023.116795. Epub 2023 Dec 29.

Authors

Affiliations

¹ Laboratory of Animal Molecular Morphology, Department of Animal Science, Graduate School of Agricultural Science, Kobe University, 1-1 Rokkodai, Nada, Kobe, Hyogo 657-8501, Japan.
² Faculty of Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan. Electronic address: thirano@cts.u-toyama.ac.jp.
³ Laboratory of Histophysiology, Department of Animal Science, Graduate School of Agricultural Science, Kobe University, 1-1 Rokkodai, Nada, Kobe, Hyogo 657-8501, Japan.
⁴ Laboratory of Toxicology, Department of Environmental Veterinary Sciences, Faculty of Veterinary Medicine, Hokkaido University, Kita 18, Nishi 9, Kita-ku, Sapporo, Hokkaido 060-0818, Japan; Translational Research Unit, Veterinary Teaching Hospital, Faculty of Veterinary Medicine, Hokkaido University, Kita 18, Nishi 9, Kita-ku, Sapporo, Hokkaido 060-0818, Japan; One Health Research Center, Hokkaido University, Kita 18, Nishi 9, Kita-ku, Sapporo 060-0818, Japan; Water Research Group, Unit for Environmental Sciences and Management, North-West University, Potchefstroom, South Africa.
⁵ Laboratory of Animal Molecular Morphology, Department of Animal Science, Graduate School of Agricultural Science, Kobe University, 1-1 Rokkodai, Nada, Kobe, Hyogo 657-8501, Japan. Electronic address: nobhoshi@kobe-u.ac.jp.

PMID: 38160895
DOI: 10.1016/j.taap.2023.116795

Abstract

Recent research has demonstrated the toxicity of neonicotinoid pesticides (NNs) in mammals through their interaction with nicotinic acetylcholine receptors (nAChRs). These effects are reported to extend to the intestinal microbiota as well. In addition, environmental stress affects the expression of nAChRs, which may alter sensitivity to NNs. In this study, we analyzed the intestinal microbiota of mice exposed to clothianidin (CLO), a type of NN, under environmental stress, and aimed to clarify the effects of such combined exposure on the intestinal microbiota. C57BL/6N male mice (9 weeks old) were subchronically administered a no-observed-adverse-effect-level (NOAEL) CLO-mixed rehydration gel for 29 days and simultaneously subjected to chronic unpredictable mild stress (CUMS). After the administration period, cecum contents were collected and analyzed by 16S rRNA sequencing for intestinal microbiota. CLO exposure alone resulted in alterations in the relative abundance of Alistipes and ASF356, which produce short-chain fatty acids. The addition of CUMS amplified these changes. On the other hand, CLO alone did not affect the relative abundance of Lactobacillus, but the abundance decreased when CUMS was added. This study revealed that the combined exposure to CLO and stress not only amplifies their individual effects on intestinal microbiota but also demonstrates combined and multifaceted toxicities.

Keywords: Clothianidin; Dysbiosis; Environmental stress; Microbiota; Neonicotinoid; nAChR.

MeSH terms

Animals
Gastrointestinal Microbiome*
Guanidines*
Male
Mammals
Mice
Mice, Inbred C57BL
Neonicotinoids / toxicity
Pesticides* / toxicity
RNA, Ribosomal, 16S / genetics
Receptors, Nicotinic*
Thiazoles*

Substances

clothianidin
Pesticides
RNA, Ribosomal, 16S
Neonicotinoids
Receptors, Nicotinic
Guanidines
Thiazoles