Exploration of Neuroscience

Table 1. Effects of pesticides on health and epigenetics

Pesticide			Risks to human health		Epigenetics
Type	Reagents	Action	Diseases and health hazards	References	Epigenetic actions	Animal type	References
Organochlorine	Carbon tetrachloride Chlordane DDT DDE (metabolite of DDT) Dieldrin Heptachlor Hexachlorocyclohexanemethoxychlor Vinclozoin	Insecticide	Growth Premature birth Abortion Prostate cancer Leukemia PD Thyroid disorders Amyotrophic lateral sclerosis	[28–38]	DNA methylation (methoxychlor, vinclozoin, DDT, and DDE) Histone modification (dieldrin)	In vitro (mesencephalic, dopaminergic neuronal, and cells) Rat Mouse embryo Human	[39–45]
Organophosphorus	Acephate Chlorpyrifos Coumaphos Diazinon Dichlorvos Fonofos Parathion Methyl parathion Malathion Phosmet Triazophos	Insecticide	Brain and neurological developmental abnormalities in infants Deintellectualization Increased incidence of attention deficit hyperactivity disorder Lung cancer Lymphoma Leukemia Asthma PD Alzheimer’s disease	[46–55]	microRNA expression (dichlorvos and triazophos)	In vitro (porcine kidney and epithelial cells) Zebrafish	[56, 57]
Organophosphorus		Weeding	Carcinogenesis Reproductive dysfunction Endocrine disruption Allergic rhinitis	[58–61]	DNA methylation Histone modification microRNA expression	Japanese medaka (oryzias latipes) In vitro (PBMC and mammalian stem cell) Rats Mouse	[62–67]
Carbamate	Glyphosate Aldicarb Carbaryl Methiocarb Pirimicarb Mancozeb Maneb Thiocarbamate Propoxur	Weeding	Neurotoxicity Thyroid disease Developmental abnormalities	[68–70]	Histone modifications (propoxur)	In vitro (gastric cells)	[71]
Pyrethroids	Cyhalothrin Cypermethrin Deltamethrin Permethrin	Insecticide	Endocrine disruption	[72, 73]	DNA methylation	Human (blood)	[74]
Neonicotinoids	Clothianidin Imidacloprid Thiamethoxam	Insecticide	Abnormal neurodevelopment	[75]	Histone modifications	Mouse	[76]
Bipyridinium	Paraquat	Weeding	Neurotoxicity PD	[77]	Histone modifications	In vitro [immortalized rat, mesencephalic dopaminergic cells (N27 cells)]	[45, 78]

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DDE: dichlorodiphenyldichloroethylene; PBMC: peripheral blood mononuclear cells; PD: Parkinson’s disease

Declarations

Acknowledgments

Thanks are due to Editage (www.editage.com) for English language editing.

Author contributions

TK: Writing—original draft. MY and YN: writing—review & editing. All authors read and approved the submitted version.

Conflicts of interest

The authors declare that they have no conflicts of interest.

Ethical approval

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Consent to publication

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Availability of data and materials

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Funding

This article was supported in part by a Grant-in-Aid for Scientific Research [22K11781] from the Japan Society for the Promotion of Science. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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References

World population prospects 2022: summary of results [Internet]. New York (NY): United Nations; c2022 [cited 2023 Jul 7]. Available from: https://www.un.org/development/desa/pd/content/World-Population-Prospects-2022

Dong X, Milholland B, Vijg J. Evidence for a limit to human lifespan. Nature. 2016;538:257–9. [DOI] [PubMed]

GBD 2019 Dementia Forecasting Collaborators. Estimation of the global prevalence of dementia in 2019 and forecasted prevalence in 2050: an analysis for the Global Burden of Disease Study 2019. Lancet Public Health. 2022;7:e105–25. [DOI] [PubMed] [PMC]

Life expectancy and healthy life expectancy data by country [Internet]. Geneva: World Health Organization; c2021 [cited 2023 Jul 7]. Available from: https://apps.who.int/gho/data/view.main.SDG2016LEXv?lang=en

Williams GA, Cylus J, Roubal T, Ong P, Barber S. Sustainable health financing with an ageing population: will population ageing lead to uncontrolled health expenditure growth? [Internet]. Sagan A, Normand C, Figueras J, North J, White C, editors. Copenhagen (Denmark): European Observatory on Health Systems and Policies; 2019. [PubMed]

Goldman DP, Cutler D, Rowe JW, Michaud PC, Sullivan J, Peneva D, et al. Substantial health and economic returns from delayed aging may warrant a new focus for medical research. Health Aff (Millwood). 2013;32:1698–705. [DOI] [PubMed] [PMC]

Comprehensive survey of living conditions 2022 (Japanese only) [Internet]. Tokyo: Ministry of Health, Labour and Welfare; c2022 [cited 2023 Jul 7]. Available from: https://www.mhlw.go.jp/toukei/saikin/hw/k-tyosa/k-tyosa22/dl/05.pdf

Baldi I, Lebailly P, Mohammed-Brahim B, Letenneur L, Dartigues JF, Brochard P. Neurodegenerative diseases and exposure to pesticides in the elderly. Am J Epidemiol. 2003;157:409–14. [DOI] [PubMed]

Roberts JR, Karr CJ; Council On Environmental Health. Pesticide exposure in children. Pediatrics. 2012;130:e1765–88. Erratum in: Pediatrics. 2013;131:1013–4. [DOI] [PubMed] [PMC]

10.

Brehm E, Flaws JA. Transgenerational effects of endocrine-disrupting chemicals on male and female reproduction. Endocrinology. 2019;160:1421–35. [DOI] [PubMed] [PMC]

11.

Singh RK, Chang HW, Yan D, Lee KM, Ucmak D, Wong K, et al. Influence of diet on the gut microbiome and implications for human health. J Transl Med. 2017;15:73. [DOI] [PubMed] [PMC]

12.

Łuc M, Misiak B, Pawłowski M, Stańczykiewicz B, Zabłocka A, Szcześniak D, et al. Gut microbiota in dementia. Critical review of novel findings and their potential application. Prog Neuropsychopharmacol Biol Psychiatry. 2021;104:110039. [DOI] [PubMed]

13.

Sharma A, Kumar V, Shahzad B, Tanveer M, Sidhu GPS, Handa N, et al. Worldwide pesticide usage and its impacts on ecosystem. SN Appl Sci. 2019;1:1446. [DOI]

14.

Berg G. Plant-microbe interactions promoting plant growth and health: perspectives for controlled use of microorganisms in agriculture. Appl Microbiol Biotechnol. 2009;84:11–8. [DOI] [PubMed]

15.

Baligar VC, Fageria NK, He ZL. Nutrient use efficiency in plants. Commun Soil Sci Plant Anal. 2001;32:921–50. [DOI]

16.

Sangiorgio D, Spinelli F, Vandelle E. The unseen effect of pesticides: the impact on phytobiota structure and functions. Front Agron. 2022;4:936032. [DOI]

17.

Narenderan ST, Meyyanathan SN, Babu B. Review of pesticide residue analysis in fruits and vegetables. Pre-treatment, extraction and detection techniques. Food Res Int. 2020;133:109141. [DOI] [PubMed]

18.

Umapathi R, Ghoreishian SM, Sonwal S, Rani GM, Huh YS. Portable electrochemical sensing methodologies for on-site detection of pesticide residues in fruits and vegetables. Coord Chem Rev. 2022;453:214305. [DOI]

19.

Jiang J, Zou S, Ma L, Wang S, Liao J, Zhang Z. Surface-enhanced Raman scattering detection of pesticide residues using transparent adhesive tapes and coated silver nanorods. ACS Appl Mater Interfaces. 2018;10:9129–35. [DOI] [PubMed]

20.

Historical development of pesticides in Japan [Internet]. Tokyo: Center of the History of Japanese Industrial Technology; c2009 [cited 2023 Jul 7]. Available from: https://sts.kahaku.go.jp/diversity/document/system/pdf/077_e.pdf

21.

Bajwa U, Sandhu KS. Effect of handling and processing on pesticide residues in food- a review. J Food Sci Technol. 2014;51:201–20. [DOI] [PubMed] [PMC]

22.

Pimentel D. Environmental and economic costs of the application of pesticides primarily in the United States. Environ Dev Sustain. 2005;7:229–52. [DOI]

23.

Carson R. Silent spring. 40th editon. Boston: Houghton Mifflin Company; 2002.

24.

The use of DDT in malaria vector control: WHO position statement [Internet]. Geneva: World Health Organization; c2011 [cited 2023 Jul 7]. Available from: https://iris.who.int/bitstream/handle/10665/69945/WHO_HTM_GMP_2011_eng.pdf?sequence=1

25.

Li C, Yang L, Shi M, Liu G. Persistent organic pollutants in typical lake ecosystems. Ecotoxicol Environ Saf. 2019;180:668–78. [DOI] [PubMed]

26.

Thompson LA, Darwish WS, Ikenaka Y, Nakayama SM, Mizukawa H, Ishizuka M. Organochlorine pesticide contamination of foods in Africa: incidence and public health significance. J Vet Med Sci. 2017;79:751–64. [DOI] [PubMed] [PMC]

27.

Roberts JR, Fungicides JR. Recognition management pesticide poisonings. 6th ed. Washington: US Environmental Protection Agency; 2013.

28.

Chao HR, Wang SL, Lin TC, Chung XH. Levels of organochlorine pesticides in human milk from central Taiwan. Chemosphere. 2006;62:1774–85. [DOI] [PubMed]

29.

Lee S, Kim S, Lee HK, Lee IS, Park J, Kim HJ, et al. Contamination of polychlorinated biphenyls and organochlorine pesticides in breast milk in Korea: time-course variation, influencing factors, and exposure assessment. Chemosphere. 2013;93:1578–85. [DOI] [PubMed]

30.

Raab U, Albrecht M, Preiss U, Völkel W, Schwegler U, Fromme H. Organochlorine compounds, nitro musks and perfluorinated substances in breast milk – results from Bavarian Monitoring of Breast Milk 2007/8. Chemosphere. 2013;93:461–7. [DOI] [PubMed]

31.

Rojas-Squella X, Santos L, Baumann W, Landaeta D, Jaimes A, Correa JC, et al. Presence of organochlorine pesticides in breast milk samples from Colombian women. Chemosphere. 2013;91:733–9. [DOI] [PubMed]

32.

Pathak R, Ahmed RS, Tripathi AK, Guleria K, Sharma CS, Makhijani SD, et al. Maternal and cord blood levels of organochlorine pesticides: association with preterm labor. Clin Biochem. 2009;42:746–9. [DOI] [PubMed]

33.

Pathak R, Mustafa MD, Ahmed RS, Tripathi AK, Guleria K, Banerjee BD. Association between recurrent miscarriages and organochlorine pesticide levels. Clin Biochem. 2010;43:131–5. [DOI] [PubMed]

34.

Band PR, Abanto Z, Bert J, Lang B, Fang R, Gallagher RP, et al. Prostate cancer risk and exposure to pesticides in British Columbia farmers. Prostate. 2011;71:168–83. [DOI] [PubMed]

35.

Orsi L, Delabre L, Monnereau A, Delval P, Berthou C, Fenaux P, et al. Occupational exposure to pesticides and lymphoid neoplasms among men: results of a French case-control study. Occup Environ Med. 2009;66:291–8. [DOI] [PubMed] [PMC]

36.

Elbaz A, Clavel J, Rathouz PJ, Moisan F, Galanaud JP, Delemotte B, et al. Professional exposure to pesticides and Parkinson disease. Ann Neurol. 2009;66:494–504. [DOI] [PubMed]

37.

Kamel F, Umbach DM, Bedlack RS, Richards M, Watson M, Alavanja MCR, et al. Pesticide exposure and amyotrophic lateral sclerosis. Neurotoxicology. 2012;33:457–62. [DOI] [PubMed] [PMC]

38.

Goldner WS, Sandler DP, Yu F, Hoppin JA, Kamel F, LeVan TD. Pesticide use and thyroid disease among women in the agricultural health study. Am J Epidemiol. 2010;171:455–64. [DOI] [PubMed] [PMC]

39.

Stouder C, Paoloni-Giacobino A. Specific transgenerational imprinting effects of the endocrine disruptor methoxychlor on male gametes. Reproduction. 2011;141:207–16. [DOI] [PubMed]

40.

Zama AM, Uzumcu M. Fetal and neonatal exposure to the endocrine disruptor methoxychlor causes epigenetic alterations in adult ovarian genes. Endocrinology. 2009;150:4681–91. [DOI] [PubMed] [PMC]

41.

Kang ER, Iqbal K, Tran DA, Rivas GE, Singh P, Pfeifer GP, et al. Effects of endocrine disruptors on imprinted gene expression in the mouse embryo. Epigenetics. 2011;6:937–50. [DOI] [PubMed] [PMC]

42.

Shutoh Y, Takeda M, Ohtsuka R, Haishima A, Yamaguchi S, Fujie H, et al. Low dose effects of dichlorodiphenyltrichloroethane (DDT) on gene transcription and DNA methylation in the hypothalamus of young male rats: implication of hormesis-like effects. J Toxicol Sci. 2009;34:469–82. [DOI] [PubMed]

43.

Kim KY, Kim DS, Lee SK, Lee IK, Kang JH, Chang YS, et al. Association of low-dose exposure to persistent organic pollutants with global DNA hypomethylation in healthy Koreans. Environ Health Perspect. 2010;118:370–4. [DOI] [PubMed] [PMC]

44.

Rusiecki JA, Baccarelli A, Bollati V, Tarantini L, Moore LE, Bonefeld-Jorgensen EC. Global DNA hypomethylation is associated with high serum-persistent organic pollutants in greenlandic inuit. Environ Health Perspect. 2008;116:1547–52. [DOI] [PubMed] [PMC]

45.

Song C, Kanthasamy A, Anantharam V, Sun F, Kanthasamy AG. Environmental neurotoxic pesticide increases histone acetylation to promote apoptosis in dopaminergic neuronal cells: relevance to epigenetic mechanisms of neurodegeneration. Mol Pharmacol. 2010;77:621–32. [DOI] [PubMed] [PMC]

46.

Sanghi R, Pillai MK, Jayalekshmi TR, Nair A. Organochlorine and organophosphorus pesticide residues in breast milk from Bhopal, Madhya Pradesh, India. Hum Exp Toxicol. 2003;22:73–6. [DOI] [PubMed]

47.

Bouchard MF, Bellinger DC, Wright RO, Weisskopf MG. Attention-deficit/hyperactivity disorder and urinary metabolites of organophosphate pesticides. Pediatrics. 2010;125:e1270–7. [DOI] [PubMed] [PMC]

48.

Bouchard MF, Chevrier J, Harley KG, Kogut K, Vedar M, Calderon N, et al. Prenatal exposure to organophosphate pesticides and IQ in 7-year-old children. Environ Health Perspect. 2011;119:1189–95. [DOI] [PubMed] [PMC]

49.

Alavanja MCR, Bonner MR. Occupational pesticide exposures and cancer risk: a review. J Toxicol Environ Health B Crit Rev. 2012;15:238–63. [DOI] [PubMed] [PMC]

50.

Karunanayake CP, Spinelli JJ, McLaughlin JR, Dosman JA, Pahwa P, McDuffie HH. Hodgkin lymphoma and pesticides exposure in men: a Canadian case-control study. J Agromedicine. 2012;17:30–9. [DOI] [PubMed]

51.

Hu L, Luo D, Zhou T, Tao Y, Feng J, Mei S. The association between non-Hodgkin lymphoma and organophosphate pesticides exposure: a meta-analysis. Environ Pollut. 2017;231:319–28. [DOI] [PubMed]

52.

Freire C, Koifman S. Pesticide exposure and Parkinson’s disease: epidemiological evidence of association. Neurotoxicology. 2012;33:947–71. [DOI] [PubMed]

53.

Wang A, Cockburn M, Ly TT, Bronstein JM, Ritz B. The association between ambient exposure to organophosphates and Parkinson’s disease risk. Occup Environ Med. 2014;71:275–81. [DOI] [PubMed] [PMC]

54.

Zaganas I, Kapetanaki S, Mastorodemos V, Kanavouras K, Colosio C, Wilks MF, et al. Linking pesticide exposure and dementia: what is the evidence? Toxicology. 2013;307:3–11. [DOI] [PubMed]

55.

Hoppin JA, Umbach DM, London SJ, Henneberger PK, Kullman GJ, Coble J, et al. Pesticide use and adult-onset asthma among male farmers in the Agricultural Health Study. Eur Respir J. 2009;34:1296–303. [DOI] [PubMed] [PMC]

56.

Li S, Ran XQ, Xu L, Wang JF. microRNA and mRNA expression profiling analysis of dichlorvos cytotoxicity in porcine kidney epithelial PK15 cells. DNA Cell Biol. 2011;30:1073–83. [DOI] [PubMed]

57.

Wang X, Zhou S, Ding X, Zhu G, Guo J. Effect of triazophos, fipronil and their mixture on miRNA expression in adult zebrafish. J Environ Sci Health B. 2010;45:648–57. [DOI] [PubMed]

58.

Guyton KZ, Loomis D, Grosse Y, El Ghissassi F, Benbrahim-Tallaa L, Guha N, et al. Carcinogenicity of tetrachlorvinphos, parathion, malathion, diazinon, and glyphosate. Lancet Oncol. 2015;16:490–1. [DOI] [PubMed]

59.

Gasnier C, Dumont C, Benachour N, Clair E, Chagnon MC, Seralini GE. Glyphosate-based herbicides are toxic and endocrine disruptors in human cell lines. Toxicology. 2009;262:184–91. [DOI] [PubMed]

60.

Cassault-Meyer E, Gress S, Séralini GÉ, Galeraud-Denis I. An acute exposure to glyphosate-based herbicide alters aromatase levels in testis and sperm nuclear quality. Environ Toxicol Pharmacol. 2014;38:131–40. [DOI] [PubMed]

61.

Slager RE, Simpson SL, Levan TD, Poole JA, Sandler DP, Hoppin JA. Rhinitis associated with pesticide use among private pesticide applicators in the agricultural health study. J Toxicol Environ Health A. 2010;73:1382–93. [DOI] [PubMed] [PMC]

62.

Smith CM, Vera MKM, Bhandari RK. Developmental and epigenetic effects of Roundup and glyphosate exposure on Japanese medaka (Oryzias latipes). Aquat Toxicol. 2019;210:215–26. [DOI] [PubMed]

63.

Kwiatkowska M, Reszka E, Woźniak K, Jabłońska E, Michałowicz J, Bukowska B. DNA damage and methylation induced by glyphosate in human peripheral blood mononuclear cells (in vitro study). Food Chem Toxicol. 2017;105:93–8. [DOI] [PubMed]

64.

Woźniak E, Reszka E, Jabłońska E, Balcerczyk A, Broncel M, Bukowska B. Glyphosate affects methylation in the promoter regions of selected tumor suppressors as well as expression of major cell cycle and apoptosis drivers in PBMCs (in vitro study). Toxicol In Vitro. 2020;63:104736. [DOI] [PubMed]

65.

Lorenz V, Milesi MM, Schimpf MG, Luque EH, Varayoud J. Epigenetic disruption of estrogen receptor alpha is induced by a glyphosate-based herbicide in the preimplantation uterus of rats. Mol Cell Endocrinol. 2019;480:133–41. [DOI] [PubMed]

66.

Ji H, Xu L, Wang Z, Fan X, Wu L. Differential microRNA expression in the prefrontal cortex of mouse offspring induced by glyphosate exposure during pregnancy and lactation. Exp Ther Med. 2018;15:2457–67. [DOI] [PubMed] [PMC]

67.

Mesnage R, Ibragim M, Mandrioli D, Falcioni L, Tibaldi E, Belpoggi F, et al. Comparative toxicogenomics of glyphosate and roundup herbicides by mammalian stem cell-based genotoxicity assays and molecular profiling in Sprague-Dawley rats. Toxicol Sci. 2021;186:83–101. [DOI] [PubMed] [PMC]

68.

Morais S, Dias E, de Lourdes Pereira M. Carbamates: human exposure and health effects. In: Jokanović M, editor. The impact of pesticides. Cheyenne: Academy Press; 2012. pp. 21–38.

69.

Weldon RH, Barr DB, Trujillo C, Bradman A, Holland N, Eskenazi B. A pilot study of pesticides and PCBs in the breast milk of women residing in urban and agricultural communities of California. J Environ Monit. 2011;13:3136–44. [DOI] [PubMed]

70.

Norouzi F, Alizadeh I, Faraji M. Human exposure to pesticides and thyroid cancer: a worldwide systematic review of the literatures. Thyroid Res. 2023;16:13. [DOI] [PubMed] [PMC]

71.

Kuo HH, Shyu SS, Wang TC. Genotoxicity of low dose N-nitroso propoxur to human gastric cells. Food Chem Toxicol. 2008;46:1619–26. [DOI] [PubMed]

72.

Koureas M, Tsakalof A, Tsatsakis A, Hadjichristodoulou C. Systematic review of biomonitoring studies to determine the association between exposure to organophosphorus and pyrethroid insecticides and human health outcomes. Toxicol Lett. 2012;210:155–68. [DOI] [PubMed]

73.

Sharma A, Gill JPS, Bedi JS, Pooni PA. Monitoring of pesticide residues in human breast milk from Punjab, India and its correlation with health associated parameters. Bull Environ Contam Toxicol. 2014;93:465–71. [DOI] [PubMed]

74.

Furlong MA, Paul KC, Yan Q, Chuang YH, Cockburn MG, Bronstein JM, et al. An epigenome-wide association study of ambient pyrethroid pesticide exposures in California's central valley. Int J Hyg Environ Health. 2020;229:113569. [DOI] [PubMed] [PMC]

75.

Kimura-Kuroda J, Komuta Y, Kuroda Y, Hayashi M, Kawano H. Nicotine-like effects of the neonicotinoid insecticides acetamiprid and imidacloprid on cerebellar neurons from neonatal rats. PLoS One. 2012;7:e32432. [DOI] [PubMed] [PMC]

76.

Hartman C, Legoff L, Capriati M, Lecuyer G, Kernanec PY, Tevosian S, et al. Epigenetic effects promoted by neonicotinoid thiacloprid exposure. Front Cell Dev Biol. 2021;9:691060. [DOI] [PubMed] [PMC]

77.

Pezzoli G, Cereda E. Exposure to pesticides or solvents and risk of Parkinson disease. Neurology. 2013;80:2035–41. [DOI] [PubMed]

78.

Song C, Kanthasamy A, Jin H, Anantharam V, Kanthasamy AG. Paraquat induces epigenetic changes by promoting histone acetylation in cell culture models of dopaminergic degeneration. Neurotoxicology. 2011;32:586–95. [DOI] [PubMed] [PMC]

79.

Damalas CA, Eleftherohorinos IG. Pesticide exposure, safety issues, and risk assessment indicators. Int J Environ Res Public Health. 2011;8:1402–19. [DOI] [PubMed] [PMC]

80.

Benbrook CM. Trends in glyphosate herbicide use in the United States and globally. Environ Sci Eur. 2016;28:3. [DOI] [PubMed] [PMC]

81.

Hladik ML, Main AR, Goulson D. Environmental risks and challenges associated with neonicotinoid insecticides. Environ Sci Technol. 2018;52:3329–35. [DOI] [PubMed]

82.

Williams GM, Kroes R, Munro IC. Safety evaluation and risk assessment of the herbicide Roundup and its active ingredient, glyphosate, for humans. Regul Toxicol Pharmacol. 2000;31:117–65. [DOI] [PubMed]

83.

Ueyama J, Harada KH, Koizumi A, Sugiura Y, Kondo T, Saito I, et al. Temporal levels of urinary neonicotinoid and dialkylphosphate concentrations in Japanese women between 1994 and 2011. Environ Sci Technol. 2015;49:14522–8. [DOI] [PubMed]

84.

Osaka A, Ueyama J, Kondo T, Nomura H, Sugiura Y, Saito I, et al. Exposure characterization of three major insecticide lines in urine of young children in Japan—neonicotinoids, organophosphates, and pyrethroids. Environ Res. 2016;147:89–96. [DOI] [PubMed]

85.

Oya N, Ito Y, Ebara T, Kato S, Ueyama J, Aoi A, et al. Cumulative exposure assessment of neonicotinoids and an investigation into their intake-related factors in young children in Japan. Sci Total Environ. 2021;750:141630. [DOI] [PubMed]

86.

Ikenaka Y, Miyabara Y, Ichise T, Nakayama S, Nimako C, Ishizuka M, et al. Exposures of children to neonicotinoids in pine wilt disease control areas. Environ Toxicol Chem. 2019;38:71–9. [DOI] [PubMed]

87.

Ichikawa G, Kuribayashi R, Ikenaka Y, Ichise T, Nakayama SMM, Ishizuka M, et al. LC-ESI/MS/MS analysis of neonicotinoids in urine of very low birth weight infants at birth. PLoS One. 2019;14:e0219208. [DOI] [PubMed] [PMC]

88.

Alengebawy A, Abdelkhalek ST, Qureshi SR, Wang MQ. Heavy metals and pesticides toxicity in agricultural soil and plants: ecological risks and human health implications. Toxics. 2021;9:42. [DOI] [PubMed] [PMC]

89.

Kim KH, Kabir E, Jahan SA. Exposure to pesticides and the associated human health effects. Sci Total Environ. 2017;575:525–35. [DOI] [PubMed]

90.

Rani L, Thapa K, Kanojia N, Sharma N, Singh S, Grewal AS, et al. An extensive review on the consequences of chemical pesticides on human health and environment. J Clean Prod. 2021;283:124657. [DOI]

91.

Cox-Foster DL, Conlan S, Holmes EC, Palacios G, Evans JD, Moran NA, et al. A metagenomic survey of microbes in honey bee colony collapse disorder. Science. 2007;318:283–7. [DOI] [PubMed]

92.

Henry M, Béguin M, Requier F, Rollin O, Odoux JF, Aupinel P, et al. A common pesticide decreases foraging success and survival in honey bees. Science. 2012;336:348–50. [DOI] [PubMed]

93.

Whitehorn PR, O’Connor S, Wackers FL, Goulson D. Neonicotinoid pesticide reduces bumble bee colony growth and queen production. Science. 2012;336:351–2. [DOI] [PubMed]

94.

Gill RJ, Ramos-Rodriguez O, Raine NE. Combined pesticide exposure severely affects individual- and colony-level traits in bees. Nature. 2012;491:105–8. [DOI] [PubMed] [PMC]

95.

Tomizawa M, Casida JE. Neonicotinoid insecticide toxicology: mechanisms of selective action. Annu Rev Pharmacol Toxicol. 2005;45:247–68. [DOI] [PubMed]

96.

Hurst R, Rollema H, Bertrand D. Nicotinic acetylcholine receptors: from basic science to therapeutics. Pharmacol Ther. 2013;137:22–54. [DOI] [PubMed]

97.

Matsuda K, Buckingham SD, Kleier D, Rauh JJ, Grauso M, Sattelle DB. Neonicotinoids: insecticides acting on insect nicotinic acetylcholine receptors. Trends Pharmacol Sci. 2001;22:573–80. [DOI] [PubMed]

98.

Kalamida D, Poulas K, Avramopoulou V, Fostieri E, Lagoumintzis G, Lazaridis K, et al. Muscle and neuronal nicotinic acetylcholine receptors. Structure, function and pathogenicity. FEBS J. 2007;274:3799–845. [DOI] [PubMed]

99.

Dwyer JB, McQuown SC, Leslie FM. The dynamic effects of nicotine on the developing brain. Pharmacol Ther. 2009;122:125–39. [DOI] [PubMed] [PMC]

100.

Anadón A, Ares I, Martínez M, Martínez-Larrañaga MR, Martínez MA. Chapter four - neurotoxicity of neonicotinoids. Adv Neurotoxicol. 2020;4:167–207. [DOI]

101.

Jones AK, Sattelle DB. Diversity of insect nicotinic acetylcholine receptor subunits. Adv Exp Med Biol. 2010;683:25–43. [DOI] [PubMed]

102.

Houchat JN, Cartereau A, Le Mauff A, Taillebois E, Thany SH. An overview on the effect of neonicotinoid insecticides on mammalian cholinergic functions through the activation of neuronal nicotinic acetylcholine receptors. Int J Environ Res Public Health. 2020;17:3222. [DOI] [PubMed] [PMC]

103.

Li M, Fallin MD, Riley A, Landa R, Walker SO, Silverstein M, et al. The association of maternal obesity and diabetes with autism and other developmental disabilities. Pediatrics. 2016;137:e20152206. [DOI] [PubMed] [PMC]

104.

Zhang H, Bai X, Zhang T, Song S, Zhu H, Lu S, et al. Neonicotinoid insecticides and their metabolites can pass through the human placenta unimpeded. Environ Sci Technol. 2022;56:17143–52. [DOI] [PubMed]

105.

Pan C, Yu J, Yao Q, Lin N, Lu Z, Zhang Y, et al. Prenatal neonicotinoid insecticides exposure, oxidative stress, and birth outcomes. Environ Int. 2022;163:107180. [DOI] [PubMed]

106.

Hirano T, Yanai S, Takada T, Yoneda N, Omotehara T, Kubota N, et al. NOAEL-dose of a neonicotinoid pesticide, clothianidin, acutely induce anxiety-related behavior with human-audible vocalizations in male mice in a novel environment. Toxicol Lett. 2018;282:57–63. [DOI] [PubMed]

107.

Yoneda N, Takada T, Hirano T, Yanai S, Yamamoto A, Mantani Y, et al. Peripubertal exposure to the neonicotinoid pesticide dinotefuran affects dopaminergic neurons and causes hyperactivity in male mice. J Vet Med Sci. 2018;80:634–7. [DOI] [PubMed] [PMC]

108.

Sano K, Isobe T, Yang J, Win-Shwe TT, Yoshikane M, Nakayama SF, et al. In utero and lactational exposure to acetamiprid induces abnormalities in socio-sexual and anxiety-related behaviors of male mice. Front Neurosci. 2016;10:228. [DOI] [PubMed] [PMC]

109.

Ohno S, Ikenaka Y, Onaru K, Kubo S, Sakata N, Hirano T, et al. Quantitative elucidation of maternal-to-fetal transfer of neonicotinoid pesticide clothianidin and its metabolites in mice. Toxicol Lett. 2020;322:32–8. [DOI] [PubMed]

110.

Maeda M, Kitauchi S, Hirano T, Ikenaka Y, Nishi M, Shoda A, et al. Fetal and lactational exposure to the no-observed-adverse-effect level (NOAEL) dose of the neonicotinoid pesticide clothianidin inhibits neurogenesis and induces different behavioral abnormalities at the developmental stages in male mice. J Vet Med Sci. 2021;83:542–8. [DOI] [PubMed] [PMC]

111.

Custovic A. Chapter 3 - epidemiology of allergic diseases. In: O’Hehir RE, Holgate ST, Sheikh A, editors. Middleton's allergy essentials. Edinburgh: Elsevier; 2017. pp. 51–72.

112.

Ober C, Yao TC. The genetics of asthma and allergic disease: a 21st century perspective. Immunol Rev. 2011;242:10–30. [DOI] [PubMed] [PMC]

113.

Strachan DP. Hay fever, hygiene, and household size. BMJ. 1989;299:1259–60. [DOI] [PubMed] [PMC]

114.

Strachan DP, Golding J, Anderson HR. Regional variations in wheezing illness in British children: effect of migration during early childhood. J Epidemiol Community Health. 1990;44:231–6. [DOI] [PubMed] [PMC]

115.

Strachan DP. Family size, infection and atopy: the first decade of the “hygiene hypothesis”. Thorax. 2000;55:S2–10. [DOI] [PubMed] [PMC]

116.

von Mutius E, Fritzsch C, Weiland SK, Roll G, Magnussen H. Prevalence of asthma and allergic disorders among children in united Germany: a descriptive comparison. BMJ. 1992;305:1395–9. [DOI] [PubMed] [PMC]

117.

von Mutius E, Weiland SK, Fritzsch C, Duhme H, Keil U. Increasing prevalence of hay fever and atopy among children in Leipzig, East Germany. Lancet. 1998;351:862–6. [DOI] [PubMed]

118.

Nicolai T. Epidemiology of pollution-induced airway disease: urban/rural differences in East and West Germany. Allergy. 1997;52:26–9. [DOI] [PubMed]

119.

Ege MJ, Mayer M, Normand AC, Genuneit J, Cookson WO, Braun-Fahrlander C, et al. Exposure to environmental microorganisms and childhood asthma. N Engl J Med. 2011;364:701–9. [DOI] [PubMed]

120.

Stein MM, Hrusch CL, Gozdz J, Igartua C, Pivniouk V, Murray SE, et al. Innate immunity and asthma risk in mish and Hutterite farm children. N Engl J Med. 2016;375:411–21. [DOI] [PubMed] [PMC]

121.

Schuijs MJ, Willart MA, Vergote K, Gras D, Deswarte K, Ege MJ, et al. Farm dust and endotoxin protect against allergy through A20 induction in lung epithelial cells. Science. 2015;349:1106–10. [DOI] [PubMed]

122.

Gensollen T, Iyer SS, Kasper DL, Blumberg RS. How colonization by microbiota in early life shapes the immune system. Science. 2016;352:539–44. [DOI] [PubMed] [PMC]

123.

Rook GAW, Lowry CA, Raison CL. Microbial ‘Old Friends’, immunoregulation and stress resilience. Evol Med Public Health. 2013;2013:46–64. [DOI] [PubMed] [PMC]

124.

Rook GAW. Review series on helminths, immune modulation and the hygiene hypothesis: the broader implications of the hygiene hypothesis. Immunology. 2009;126:3–11. [DOI] [PubMed] [PMC]

125.

Murdaca G, Greco M, Borro M, Gangemi S. Hygiene hypothesis and autoimmune diseases: a narrative review of clinical evidences and mechanisms. Autoimmun Rev. 2021;20:102845. [DOI] [PubMed]

126.

Fattorusso A, Di Genova L, Dell’Isola GB, Mencaroni E, Esposito S. Autism spectrum disorders and the gut microbiota. Nutrients. 2019;11:521. [DOI] [PubMed] [PMC]

127.

Meltzer A, Van de Water J. The role of the immune system in autism spectrum disorder. Neuropsychopharmacology. 2017;42:284–98. [DOI] [PubMed] [PMC]

128.

Kier LD, Kirkland DJ. Review of genotoxicity studies of glyphosate and glyphosate-based formulations. Crit Rev Toxicol. 2013;43:283–315. [DOI] [PubMed]

129.

Richards TA, Dacks JB, Campbell SA, Blanchard JL, Foster PG, McLeod R, et al. Evolutionary origins of the eukaryotic shikimate pathway: gene fusions, horizontal gene transfer, and endosymbiotic replacements. Eukaryot Cell. 2006;5:1517–31. [DOI] [PubMed] [PMC]

130.

Mathew SA, Muola A, Saikkonen K, Saloniemi I, Helander M, Puigbo P. Quantification of the potential impact of glyphosate-based products on microbiomes. J Vis Exp. 2022;179:e63109. [DOI] [PubMed]

131.

Shehata AA, Schrödl W, Aldin AA, Hafez HM, Krüger M. The effect of glyphosate on potential pathogens and beneficial members of poultry microbiota in vitro. Curr Microbiol. 2013;66:350–8. [DOI] [PubMed]

132.

Mao Q, Manservisi F, Panzacchi S, Mandrioli D, Menghetti I, Vornoli A, et al. The Ramazzini Institute 13-week pilot study on glyphosate and Roundup administered at human-equivalent dose to Sprague Dawley rats: effects on the microbiome. Environ Health. 2018;17:50. [DOI] [PubMed] [PMC]

133.

Puigbò P, Leino LI, Rainio MJ, Saikkonen K, Saloniemi I, Helander M. Does glyphosate affect the human microbiota? Life (Basel). 2022;12:707. [DOI] [PubMed] [PMC]

134.

Rooks MG, Garrett WS. Gut microbiota, metabolites and host immunity. Nat Rev Immunol. 2016;16:341–52. [DOI] [PubMed] [PMC]

135.

Kalinkovich A, Livshits G. A cross talk between dysbiosis and gut-associated immune system governs the development of inflammatory arthropathies. Semin Arthritis Rheum. 2019;49:474–84. [DOI] [PubMed]

136.

Mousa WK, Chehadeh F, Husband S. Microbial dysbiosis in the gut drives systemic autoimmune diseases. Front Immunol. 2022;13:906258. [DOI] [PubMed] [PMC]

137.

Hughes HK, Rose D, Ashwood P. The gut microbiota and dysbiosis in autism spectrum disorders. Curr Neurol Neurosci Rep. 2018;18:81. [DOI] [PubMed] [PMC]

138.

Noto D, Miyake S. Gut dysbiosis and multiple sclerosis. Clin Immunol. 2022;235:108380. [DOI] [PubMed]

139.

Sasayama D, Kuge R, Toibana Y, Honda H. Trends in diagnosed attention-deficit/hyperactivity disorder among children, adolescents, and adults in Japan from April 2010 to March 2020. JAMA Netw Open. 2022;5:e2234179. [DOI] [PubMed] [PMC]

140.

Xu G, Strathearn L, Liu B, Yang B, Bao W. Twenty-year trends in diagnosed attention-deficit/hyperactivity disorder among US children and adolescents, 1997-2016. JAMA Netw Open. 2018;1:e181471. [DOI] [PubMed] [PMC]

141.

Swanson NL, Leu A, Abrahamson J, Wallet B. Genetically engineered crops, glyphosate and the deterioration of health in the United States of America. JOS. 2014;9:6–37.

142.

Shaw W. Elevated urinary glyphosate and clostridia metabolites with altered dopamine metabolism in triplets with autistic spectrum disorder or suspected seizure disorder: a case study. Integr Med (Encinitas). 2017;16:50–7. [PubMed] [PMC]

143.

Argou-Cardozo I, Zeidán-Chuliá F. Clostridium bacteria and autism spectrum conditions: a systematic review and hypothetical contribution of environmental glyphosate levels. Med Sci (Basel). 2018;6:29. [DOI] [PubMed] [PMC]

144.

Guo P, Zhang K, Ma X, He P. Clostridium species as probiotics: potentials and challenges. J Anim Sci Biotechnol. 2020;11:24. [DOI] [PubMed] [PMC]

145.

von Ehrenstein OS, Ling C, Cui X, Cockburn M, Park AS, Yu F, et al. Prenatal and infant exposure to ambient pesticides and autism spectrum disorder in children: population based case-control study. BMJ. 2019;364:l962. Erratum in: BMJ. 2019;365:l4032. [DOI] [PubMed] [PMC]

146.

Aitbali Y, Ba-M’hamed S, Elhidar N, Nafis A, Soraa N, Bennis M. Glyphosate based- herbicide exposure affects gut microbiota, anxiety and depression-like behaviors in mice. Neurotoxicol Teratol. 2018;67:44–9. [DOI] [PubMed]

147.

Cheroni C, Caporale N, Testa G. Autism spectrum disorder at the crossroad between genes and environment: contributions, convergences, and interactions in ASD developmental pathophysiology. Mol Autism. 2020;11:69. [DOI] [PubMed] [PMC]

148.

Gallegos CE, Baier CJ, Bartos M, Bras C, Dominguez S, Monaco N, et al. Perinatal glyphosate-based herbicide exposure in rats alters brain antioxidant status, glutamate and acetylcholine metabolism and affects recognition memory. Neurotox Res. 2018;34:363–74. [DOI] [PubMed]

149.

Removal of glyphosate from global usage [Internet]. London: FIGO; c2019 [cited 2023 Jul 7]. Available from: https://www.figo.org/removal-glyphosate-global-usage

150.

Bird A. Perceptions of epigenetics. Nature. 2007;447:396–8. [DOI] [PubMed]

151.

Waterland RA, Michels KB. Epigenetic epidemiology of the developmental origins hypothesis. Annu Rev Nutr. 2007;27:363–88. [DOI] [PubMed]

152.

Kubsad D, Nilsson EE, King SE, Sadler-Riggleman I, Beck D, Skinner MK. Assessment of glyphosate induced epigenetic transgenerational inheritance of pathologies and sperm epimutations: generational toxicology. Sci Rep. 2019;9:6372. [DOI] [PubMed] [PMC]

153.

Milesi MM, Lorenz V, Pacini G, Repetti MR, Demonte LD, Varayoud J, et al. Perinatal exposure to a glyphosate-based herbicide impairs female reproductive outcomes and induces second-generation adverse effects in Wistar rats. Arch Toxicol. 2018;92:2629–43. [DOI] [PubMed]

154.

Jakimiuk AJ, Weitsman SR, Yen HW, Bogusiewicz M, Magoffin DA. Estrogen receptor α and β expression in theca and granulosa cells from women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2002;87:5532–8. [DOI]

155.

Bulun SE, Monsavais D, Pavone ME, Dyson M, Xue Q, Attar E, et al. Role of estrogen receptor-β in endometriosis. Semin Reprod Med. 2012;30:39–45. [DOI] [PubMed] [PMC]

156.

Botelho MC, Alves H, Barros A, Rinaldi G, Brindley PJ, Sousa M. The role of estrogens and estrogen receptor signaling pathways in cancer and infertility: the case of schistosomes. Trends Parasitol. 2015;31:246–50. [DOI] [PubMed]

157.

Gomez AL, Altamirano GA, Leturia J, Bosquiazzo VL, Muñoz-de-Toro M, Kass L. Male mammary gland development and methylation status of estrogen receptor alpha in Wistar rats are modified by the developmental exposure to a glyphosate-based herbicide. Mol Cell Endocrinol. 2019;481:14–25. [DOI] [PubMed]

158.

Kim G, Clarke CR, Larose H, Tran HT, Haak DC, Zhang L, et al. Herbicide injury induces DNA methylome alterations in Arabidopsis. PeerJ. 2017;5:e3560. [DOI] [PubMed] [PMC]

159.

Li B, Cai H, Liu K, An B, Wang R, Yang F, et al. DNA methylation alterations and their association with high temperature tolerance in rice anthesis. J Plant Growth Regul. 2023;42:780–94. [DOI]

160.

de Lima F, Boldt ABW, Kava VM, Galli-Terasawa LV, Adamoski D. Epigenetics’ role in the common bean (Phaseolus vulgaris L.) and soybean (Glycine max (L.) Merr.) nodulation: a review. Plant Mol Biol Rep. 2022;40:471–81. [DOI]

161.

Latchney SE, Fields AM, Susiarjo M. Linking inter-individual variability to endocrine disruptors: insights for epigenetic inheritance. Mamm Genome. 2018;29:141–52. [DOI] [PubMed] [PMC]

162.

Kassotis CD, Vandenberg LN, Demeneix BA, Porta M, Slama R, Trasande L. Endocrine-disrupting chemicals: economic, regulatory, and policy implications. Lancet Diabetes Endocrinol. 2020;8:719–30. [DOI] [PubMed] [PMC]

163.

Niu Y, DesMarais TL, Tong Z, Yao Y, Costa M. Oxidative stress alters global histone modification and DNA methylation. Free Radic Biol Med. 2015;82:22–8. [DOI] [PubMed] [PMC]

164.

Kass SU, Pruss D, Wolffe AP. How does DNA methylation repress transcription? Trends Genet. 1997;13:444–9. [DOI] [PubMed]

165.

Horsthemke B. A critical view on transgenerational epigenetic inheritance in humans. Nat Commun. 2018;9:2973. [DOI] [PubMed] [PMC]

166.

Sun W, von Meyenn F, Peleg-Raibstein D, Wolfrum C. Environmental and nutritional effects regulating adipose tissue function and metabolism across generations. Adv Sci (Weinh). 2019;6:1900275. [DOI] [PubMed] [PMC]

167.

Pang SYY, Ho PWL, Liu HF, Leung CT, Li L, Chang EES, et al. The interplay of aging, genetics and environmental factors in the pathogenesis of Parkinson’s disease. Transl Neurodegener. 2019;8:23. [DOI] [PubMed] [PMC]

168.

Zheng Q, Yin J, Zhu L, Jiao L, Xu Z. Reversible Parkinsonism induced by acute exposure glyphosate. Parkinsonism Relat Disord. 2018;50:121. [DOI] [PubMed]

169.

Barbosa ER, Leiros da Costa MD, Bacheschi LA, Scaff M, Leite CC. Parkinsonism after glycine-derivate exposure. Mov Disord. 2001;16:565–8. [DOI] [PubMed]

170.

Eriguchi M, Iida K, Ikeda S, Osoegawa M, Nishioka K, Hattori N, et al. Parkinsonism relating to intoxication with glyphosate. Intern Med. 2019;58:1935–8. [DOI] [PubMed] [PMC]

171.

Cattani D, Cesconetto PA, Tavares MK, Parisotto EB, De Oliveira PA, Rieg CEH, et al. Developmental exposure to glyphosate-based herbicide and depressive-like behavior in adult offspring: implication of glutamate excitotoxicity and oxidative stress. Toxicology. 2017;387:67–80. [DOI] [PubMed]

172.

Ait Bali Y, Ba-Mhamed S, Bennis M. Behavioral and immunohistochemical study of the effects of subchronic and chronic exposure to glyphosate in mice. Front Behav Neurosci. 2017;11:146. [DOI] [PubMed] [PMC]

173.

Spivey A. Rotenone and paraquat linked to Parkinson’s disease: human exposure study supports years of animal studies. Environ Health Perspect. 2011;119:A259. [DOI] [PubMed] [PMC]

174.

Elbaz A, Moisan F. The scientific bases to consider Parkinson’s disease an occupational disease in agriculture professionals exposed to pesticides in France. J Epidemiol Community Health. 2016;70:319–21. [DOI] [PubMed]

175.

Sims R, Hill M, Williams J. The multiplex model of the genetics of Alzheimer’s disease. Nat Neurosci. 2020;23:311–22. [DOI] [PubMed]

176.

Yan D, Zhang Y, Liu L, Yan H. Pesticide exposure and risk of Alzheimer’s disease: a systematic review and meta-analysis. Sci Rep. 2016;6:32222. [DOI] [PubMed] [PMC]

177.

Ismail AA, Bodner TE, Rohlman DS. Neurobehavioral performance among agricultural workers and pesticide applicators: a meta-analytic study. Occup Environ Med. 2012;69:457–64. [DOI] [PubMed] [PMC]

178.

Mackenzie Ross SJ, Brewin CR, Curran HV, Furlong CE, Abraham-Smith KM, Harrison V. Neuropsychological and psychiatric functioning in sheep farmers exposed to low levels of organophosphate pesticides. Neurotoxicol Teratol. 2010;32:452–9. [DOI] [PubMed] [PMC]

179.

Nagy K, Duca RC, Lovas S, Creta M, Scheepers PTJ, Godderis L, et al. Systematic review of comparative studies assessing the toxicity of pesticide active ingredients and their product formulations. Environ Res. 2020;181:108926. [DOI] [PubMed]

180.

Mesnage R, Teixeira M, Mandrioli D, Falcioni L, Ibragim M, Ducarmon QR, et al. Multi-omics phenotyping of the gut-liver axis reveals metabolic perturbations from a low-dose pesticide mixture in rats. Commun Biol. 2021;4:471. [DOI] [PubMed] [PMC]

181.

Mogili UMR, Deepak BBVL. Review on application of drone systems in precision agriculture. Procedia Comput Sci. 2018;133:502–9. [DOI]

182.

Zwetsloot HM, Lisette N, Jansen K. The general ban on aerial spraying of pesticides of the European Union: the policy-making process between 1993-2009. Wageningen: Wageningen University; 2018.

183.

Damalas CA, Koutroubas SD. Farmers’ exposure to pesticides: toxicity types and ways of prevention. Toxics. 2016;4:1. [DOI] [PubMed] [PMC]

184.

Bisanz JE, Upadhyay V, Turnbaugh JA, Ly K, Turnbaugh PJ. Meta-analysis reveals reproducible gut microbiome alterations in response to a high-fat diet. Cell Host Microbe. 2019;26:265–72.e4. [DOI] [PubMed] [PMC]

185.

Gacesa R, Kurilshikov A, Vich Vila A, Sinha T, Klaassen MAY, Bolte LA, et al. Environmental factors shaping the gut microbiome in a Dutch population. Nature. 2022;604:732–9. [DOI] [PubMed]

186.

Sonnenburg ED, Sonnenburg JL. The ancestral and industrialized gut microbiota and implications for human health. Nat Rev Microbiol. 2019;17:383–90. [DOI] [PubMed]

187.

Di Gesù CM, Matz LM, Bolding IJ, Fultz R, Hoffman KL, Gammazza AM, et al. Maternal gut microbiota mediate intergenerational effects of high-fat diet on descendant social behavior. Cell Rep. 2022;41:111461. Erratum in: Cell Rep. 2023;42:112498. [DOI] [PubMed] [PMC]

188.

DeGruttola AK, Low D, Mizoguchi A, Mizoguchi E. Current understanding of dysbiosis in disease in human and animal models. Inflamm Bowel Dis. 2016;22:1137–50. [DOI] [PubMed] [PMC]

189.

Hawkes C, Ruel M. The links between agriculture and health: an intersectoral opportunity to improve the health and livelihoods of the poor. Bull World Health Organ. 2006;84:984–90. [DOI] [PubMed] [PMC]

190.

Ueyama J, Hayashi M, Hirayama M, Nishiwaki H, Ito M, Saito I, et al. Effects of pesticide intake on gut microbiota and metabolites in healthy adults. Int J Environ Res Public Health. 2022;20:213. [DOI] [PubMed] [PMC]

191.

Brenner S. The genetics of Caenorhabditis elegans. Genetics. 1974;77:71–94. [DOI] [PubMed] [PMC]

192.

Melnikov K, Kucharíková S, Bárdyová Z, Botek N, Kaiglová A. Applications of a powerful model organism Caenorhabditis elegans to study the neurotoxicity induced by heavy metals and pesticides. Physiol Res. 2023;72:149–66. [DOI] [PubMed] [PMC]

193.

Huang P, Liu SS, Wang ZJ, Ding TT, Tao MT, Gu ZW. Study on the characterization of pesticide modes of action similarity and the multi-endpoint combined toxicity of pesticide mixtures to Caenorhabditis elegans. Sci Total Environ. 2023;893:164918. [DOI] [PubMed]

194.

Raley-Susman KM. Examining the effect of pesticides on Caenorhabditis elegans neurons. J Vis Exp. 2022;183:e63845. [DOI] [PubMed]

195.

Nono M, Kishimoto S, Sato-Carlton A, Carlton PM, Nishida E, Uno M. Intestine-to-germline transmission of epigenetic information intergenerationally ensures systemic stress Resistance in C. elegans. Cell Rep. 2020;30:3207–17.e4. [DOI] [PubMed]

196.

Alexander AG, Marfil V, Li C. Use of Caenorhabditis elegans as a model to study Alzheimer’s disease and other neurodegenerative diseases. Front Genet. 2014;5:279. [DOI] [PubMed] [PMC]

197.

Cooper JF, Van Raamsdonk JM. Modeling Parkinson's disease in C. elegans. J Parkinsons Dis. 2018;8:17–32. [DOI] [PubMed] [PMC]

198.

Komura T, Aoki M, Kotoura S, Nishikawa Y. Protective effect of Lactococcus laudensis and Pediococcus parvulus against neuropathy due to amyloid-beta in Caenorhabditis elegans. Biomed Pharmacother. 2022;155:113769. [DOI] [PubMed]