Next-generation effects of fetal and lactational exposure to the neonicotinoid pesticide clothianidin on the immune system and gut microbiota

Abstract

Recently, the effects of exposure to clothianidin (CLO) on the thymus and gut microbiota have become clear, but no report has examined its next-generation impacts. Pregnant C57BL/6N mice were administered a no-observed-adverse-effect-level dose of CLO until weaning. We examined CLO's effects on the gut microbiota and immune organs of dams and their 3-and 10-week-old male offspring. CLO administration led to several alterations of the top 30 bacterial genera in the gut microbiota in dams and 3-week-old mice. Compared to controls, 10-week-old mice had more thymic Hassall's corpuscles, and both dams and 10-week-old mice had fewer macrophages. These results suggest that fetal and lactational CLO exposure may affect the immune system and gut microbiota of the next generation.

Effects of exposure to the neonicotinoid pesticide clothianidin on α-defensin secretion and gut microbiota in mice

“…Subsequently, questions arose about the reproductive toxicity of NNs [ 17 , 21 , 25 , 47 , 53 ], their neurotoxicity and involvement in cognitive‒emotional alterations [ 14 , 16 , 17 , 18 , 20 , 26 , 27 , 33 , 44 , 45 , 55 ], and their safety, even at the no-observed-adverse-effect level (NOAEL). Recently, subchronic exposure to clothianidin (CLO), a type of NN, has been reported to disrupt the intestinal microbiota of rats [ 35 ] and mice [ 30 , 56 ]. CLO may affect the host via dysbiosis, as reduced diversity of the gut microbiota (dysbiosis) is associated with immunomodulatory dysfunction [ 37 ] and neurological disorders [ 4 ].…”

“…Cecal contents were stored at −80°C until 16S rRNA analysis and cryptdin-1 (Crp1, a major α-defensin in mice) quantification. The 16S rRNA analysis was performed as previously reported [ 30 ]. Briefly, a nucleic acid purification system (Maxwell ® RSC; Promega K.K., Tokyo, Japan) and a nucleic acid purification kit (Maxwell ® RSC Fecal Microbiome DNA Kit [AS 1700]; Promega K.K.)…”

“…We previously reported that subchronic administration of CLO to rats induced dysbiosis, leading to changes in the relative abundance of short-chain fatty acid–producing bacteria [ 35 ]. Furthermore, exposure of maternal mice to CLO resulted in alterations in the relative abundance of such bacteria within the gut microbiota of their offspring [ 30 ]. Additionally, combined exposure of mice to CLO and environmental stress altered the relative abundance of short-chain fatty acid–producing bacteria [ 56 ].…”

Effect of clothianidin exposure at the no-observed-adverse-effect level (NOAEL) in a mouse model of atopic dermatitis

“…Numerous reports indicate the involvement of α7 nAChR in the regulation of anti-inflammatory responses, with its expression observed in macrophages, T cells, B cells, mast cells, and so on [See Review 19]. Previous studies showed that exposure to clothianidin (CLO), a class of NNs, causes a decrease in rat thymus weight [ 15 ], an increase in Hassall bodies in mouse thymus [ 13 ], and dysbiosis of the intestinal microbiota [ 13 , 15 , 24 ]. It has been shown that an imbalance of the intestinal microbiota causes allergies [See Review 18 ], raising the possibility that NNs may disrupt the immune system and contribute to the development of allergic diseases.…”

Transgenerational effects of developmental neurotoxicity induced by exposure to a no-observed-adverse-effect level (NOAEL) of neonicotinoid pesticide clothianidin

“…In 2012, however, Kimura-Kuroda reported that the NNs imidacloprid (IMI) and acetamiprid (ACE) induce nAChR-mediated neuronal excitation in the cerebellar neurons of newborn rats, and it has become clear that NNs may have adverse effects on human health, especially on the developing brain [ 18 ]. Recently it was reported that birds and mammals exposed to no-observed-adverse-effect levels (NOAELs) of NNs exhibit toxic effects on reproduction, the thymus, gut microbiota, and neurobehavior [ 4 , 9 , 10 , 11 , 13 , 19 , 24 , 27 , 29 , 31 , 36 , 43 , 50 ]. In addition, NNs were detected in the urine of adults, children, and newborns [ 15 , 16 , 32 , 45 ].…”