Boedeker W, Watts M, Clausing P, Marquez E. The global distribution of acute unintentional pesticide poisoning: estimations based on a systematic review. BMC Public Health. 1875;2020:20.
Gunier RB, Bradman A, Harley KG, Kogut K, Eskenazi B. Prenatal residential proximity to agricultural pesticide use and IQ in 7-year-old children. Environ Health Perspect. 2017;125:057002.
Gonzalez-Alzaga B, Hernandez AF, Rodriguez-Barranco M, Gomez I, Aguilar-Garduno C, Lopez-Flores I, et al. Pre- and postnatal exposures to pesticides and neurodevelopmental effects in children living in agricultural communities from south-eastern Spain. Environ Int. 2015;85:229–37.
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.
Bouchard Maryse F, Chevrier J, Harley Kim G, 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.
Ntantu Nkinsa P, Muckle G, Ayotte P, Lanphear BP, Arbuckle TE, Fraser WD, et al. Organophosphate pesticides exposure during fetal development and IQ scores in 3 and 4-year old Canadian children. Environ Res. 2020;190:110023.
Rauh V, Arunajadai S, Horton M, Perera F, Hoepner L, Barr DB, et al. Seven-year neurodevelopmental scores and prenatal exposure to chlorpyrifos, a common agricultural pesticide. Environ Health Perspect. 2011;119:1196–201.
Cohn BA, La Merrill M, Krigbaum NY, Yeh G, Park J-S, Zimmermann L, et al. DDT exposure in utero and breast Cancer. J Clin Endocrinol Metab. 2015;100:2865–72.
Quirós-Alcalá L, Mehta S, Eskenazi B. Pyrethroid pesticide exposure and parental report of learning disability and attention deficit/hyperactivity disorder in U.S. children: NHANES 1999–2002. Environ Health Perspect. 2014;122:1336–42.
Viel JF, Rouget F, Warembourg C, Monfort C, Limon G, Cordier S, et al. Behavioural disorders in 6-year-old children and pyrethroid insecticide exposure: the PELAGIE mother-child cohort. Occup Environ Med. 2017;74:275–81.
Fritsche E, Grandjean P, Crofton KM, Aschner M, Goldberg A, Heinonen T, et al. Consensus statement on the need for innovation, transition and implementation of developmental neurotoxicity (DNT) testing for regulatory purposes. Toxicol Appl Pharmacol. 2018;354:3–6.
Manservisi F, Marquillas CB, Buscaroli A, Huff J, Lauriola M, Mandrioli D, et al. An integrated experimental Design for the Assessment of multiple toxicological end points in rat bioassays. Environ Health Perspect. 2017;125:289–95.
La Merrill MA, Vandenberg LN, Smith MT, Goodson W, Browne P, Patisaul HB, et al. Consensus on the key characteristics of endocrine-disrupting chemicals as a basis for hazard identification. Nat Rev Endocrinol. 2020;16:45–57.
Tsiaoussis J, Antoniou MN, Koliarakis I, Mesnage R, Vardavas CI, Izotov BN, et al. Effects of single and combined toxic exposures on the gut microbiome: current knowledge and future directions. Toxicol Lett. 2019;312:72–97.
Koppel N, Maini Rekdal V, Balskus EP. Chemical transformation of xenobiotics by the human gut microbiota. Science. 2017; 356(6344):eaag2770.
Wallace BD, Wang H, Lane KT, Scott JE, Orans J, Koo JS, et al. Alleviating cancer drug toxicity by inhibiting a bacterial enzyme. Science. 2010;330:831–5.
Zheng X, Zhao A, Xie G, Chi Y, Zhao L, Li H, et al. Melamine-induced renal toxicity is mediated by the gut microbiota. Sci Transl Med. 2013;5:172ra122.
Dethlefsen L, Huse S, Sogin ML, Relman DA. The pervasive effects of an antibiotic on the human gut microbiota, as revealed by deep 16S rRNA sequencing. Plos Biol. 2008;6:e280.
Sun L, Xie C, Wang G, Wu Y, Wu Q, Wang X, et al. Gut microbiota and intestinal FXR mediate the clinical benefits of metformin. Nat Med. 2018;24:1919–29.
Clayton TA, Baker D, Lindon JC, Everett JR, Nicholson JK. Pharmacometabonomic identification of a significant host-microbiome metabolic interaction affecting human drug metabolism. Proc Natl Acad Sci. 2009;106:14728.
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.
Asnicar F, Berry SE, Valdes AM, Nguyen LH, Piccinno G, Drew DA, et al. Microbiome connections with host metabolism and habitual diet from 1,098 deeply phenotyped individuals. Nat Med. 2021;27:321–32.
David LA, Maurice CF, Carmody RN, Gootenberg DB, Button JE, Wolfe BE, et al. Diet rapidly and reproducibly alters the human gut microbiome. Nature. 2014;505:559–63.
De Angelis M, Ferrocino I, Calabrese FM, De Filippis F, Cavallo N, Siragusa S, et al. Diet influences the functions of the human intestinal microbiome. Sci Rep. 2020;10:4247.
Apel P, Rousselle C, Lange R, Sissoko F, Kolossa-Gehring M, Ougier E. Human biomonitoring initiative (HBM4EU) - strategy to derive human biomonitoring guidance values (HBM-GVs) for health risk assessment. Int J Hyg Environ Health. 2020;230:113622.
Calafat AM: The U.S. National Health and nutrition examination survey and human exposure to environmental chemicals. Int J Hyg Environ Health. 2012;215:99–101.
Dereumeaux C, Fillol C, Charles MA, Denys S. The French human biomonitoring program: first lessons from the perinatal component and future needs. Int J Hyg Environ Health. 2017;220:64–70.
Vineis P, Chadeau-Hyam M, Gmuender H, Gulliver J, Herceg Z, Kleinjans J, et al. The exposome in practice: design of the EXPOsOMICS project. Int J Hyg Environ Health. 2017;220:142–51.
Patel CJ, Bhattacharya J, Butte AJ. An environment-wide association study (EWAS) on type 2 diabetes mellitus. Plos One. 2010;5:e10746.
Visconti A, Le Roy CI, Rosa F, Rossi N, Martin TC, Mohney RP, et al. Interplay between the human gut microbiome and host metabolism. Nat Commun. 2019;10:4505.
Mesnage R, Teixeira M, Mandrioli D, Falcioni L, Ducarmon QR, Zwittink RD, et al. Use of shotgun metagenomics and metabolomics to evaluate the impact of glyphosate or Roundup MON 52276 on the gut microbiota and serum metabolome of Sprague-Dawley rats. Environ Health Perspect. 2021;129(1):17005. https://doi.org/10.1289/EHP6990.
Verdi S, Abbasian G, Bowyer RCE, Lachance G, Yarand D, Christofidou P, et al. TwinsUK: The UK adult twin registry update. Twin Res Hum Genet. 2019;22:523–9.
Bowyer RCE, Jackson MA, Pallister T, Skinner J, Spector TD, Welch AA, et al. Use of dietary indices to control for diet in human gut microbiota studies. Microbiome. 2018;6:77.
EPIC: EPIC-Norfolk nutritional methods: food frequency questionnaire. 2017. Available from: http://www.srl.cam.ac.uk/epic/nutmethod/FFQ.shtml. Cited 2017 May 13.
Ducarmon QR, Hornung BVH, Geelen AR, Kuijper EJ, Zwittink RD. Toward standards in clinical microbiota studies: comparison of three DNA extraction methods and two bioinformatic pipelines. mSystems. 2020;5:e00547–19.
Tsoukalas D, Alegakis A, Fragkiadaki P, Papakonstantinou E, Nikitovic D, Karataraki A, et al. Application of metabolomics: focus on the quantification of organic acids in healthy adults. Int J Mol Med. 2017;40:112–20.
Tanaka K, Hine DG, West-Dull A, Lynn TB. Gas-chromatographic method of analysis for urinary organic acids. I. Retention indices of 155 metabolically important compounds. Clin Chem. 1980;26:1839–46.
Peters V, Garbade SF, Langhans CD, Hoffmann GF, Pollitt RJ, Downing M, et al. Qualitative urinary organic acid analysis: methodological approaches and performance. J Inherit Metab Dis. 2008;31:690–6.
Tsoukalas D, Alegakis AK, Fragkiadaki P, Papakonstantinou E, Tsilimidos G, Geraci F, et al. Application of metabolomics part II: focus on fatty acids and their metabolites in healthy adults. Int J Mol Med. 2019;43:233–42.
Shoari N, Dube JS. Toward improved analysis of concentration data: embracing nondetects. Environ Toxicol Chem. 2018;37:643–56.
Kuhn M. Building predictive models in R using the caret package. J Stat Softw. 2008;28:1–26.
Truong DT, Franzosa EA, Tickle TL, Scholz M, Weingart G, Pasolli E, et al. MetaPhlAn2 for enhanced metagenomic taxonomic profiling. Nat Methods. 2015;12:902–3.
Franzosa EA, McIver LJ, Rahnavard G, Thompson LR, Schirmer M, Weingart G, et al. Species-level functional profiling of metagenomes and metatranscriptomes. Nat Methods. 2018;15:962–8.
Harel O, Perkins N, Schisterman EF. The use of multiple imputation for data subject to limits of detection. Sri Lankan J Appl Stat. 2014;5:227.
Mallick H, Rahnavard A, McIver LJ, Ma S, Zhang Y, Nguyen LH, Tickle TL, Weingart G, Ren B, Schwager EH, et al.: Multivariable association discovery in population-scale Meta-omics studies. bioRxiv 2021:2021.2001.2020.427420.
Oksanen J, Blanchet FG, Friendly M, Kindt R, Legendre P, McGlinn D, Minchin PR, O'Hara R, Simpson GL, Solymos P: Vegan: Community Ecology Package. R package version 2.5–6. 2019. https://CRAN.R-project.org/package=vegan.
Anderson MJ. A new method for non-parametric multivariate analysis of variance. Austral Ecol. 2001;26:32–46.
Tollosa DN, Van Camp J, Huybrechts I, Huybregts L, Van Loco J, De Smet S, et al. Validity and reproducibility of a food frequency questionnaire for dietary factors related to colorectal cancer. Nutrients. 2017;9(11):1257.
Mesnage R, Tsakiris IN, Antoniou MN, Tsatsakis A. Limitations in the evidential basis supporting health benefits from a decreased exposure to pesticides through organic food consumption. Curr Opin Toxicol. 2020;19:50–5.
Li AJ, Kannan K. Urinary concentrations and profiles of organophosphate and pyrethroid pesticide metabolites and phenoxyacid herbicides in populations in eight countries. Environ Int. 2018;121:1148–54.
Lemke N, Murawski A, Schmied-Tobies MIH, Rucic E, Hoppe HW, Conrad A, et al. Glyphosate and aminomethylphosphonic acid (AMPA) in urine of children and adolescents in Germany - human biomonitoring results of the German environmental survey 2014-2017 (GerES V). Environ Int. 2021;156:106769.
FERA: Pesticide usage survey reports. 2016. https://secure.fera.defra.gov.uk/pusstats/surveys/index.cfm.
Mie A, Andersen HR, Gunnarsson S, Kahl J, Kesse-Guyot E, Rembiałkowska E, et al. Human health implications of organic food and organic agriculture: a comprehensive review. Environ Health. 2017;16:111.
EFSA. The 2017 European Union report on pesticide residues in food. EFSA J. 2019;17:e05743.
Colt JS, Lubin J, Camann D, Davis S, Cerhan J, Severson RK, et al. Comparison of pesticide levels in carpet dust and self-reported pest treatment practices in four US sites. J Expo Anal Environ Epidemiol. 2004;14:74–83.
Socorro J, Durand A, Temime-Roussel B, Gligorovski S, Wortham H, Quivet E. The persistence of pesticides in atmospheric particulate phase: an emerging air quality issue. Sci Rep. 2016;6:33456.
Dyk MB, Chen Z, Mosadeghi S, Vega H, Krieger R. Pilot biomonitoring of adults and children following use of chlorpyrifos shampoo and flea collars on dogs. J Environ Sci Health B. 2011;46:97–104.
Curl CL, Porter J, Penwell I, Phinney R, Ospina M, Calafat AM. Effect of a 24-week randomized trial of an organic produce intervention on pyrethroid and organophosphate pesticide exposure among pregnant women. Environ Int. 2019;132:104957.
Bradman A, Quirós-Alcalá L, Castorina R, Aguilar Schall R, Camacho J, Holland NT, et al. Effect of organic diet intervention on pesticide exposures in young children living in low-income urban and agricultural communities. Environ Health Perspect. 2015;123:1086–93.
Makris KC, Konstantinou C, Andrianou XD, Charisiadis P, Kyriacou A, Gribble MO, et al. A cluster-randomized crossover trial of organic diet impact on biomarkers of exposure to pesticides and biomarkers of oxidative stress/inflammation in primary school children. Plos One. 2019;14:e0219420.
Konstantinou C, Gaengler S, Oikonomou S, Delplancke T, Charisiadis P, Makris KC. Use of metabolomics in refining the effect of an organic food intervention on biomarkers of exposure to pesticides and biomarkers of oxidative damage in primary school children in Cyprus: a cluster-randomized cross-over trial. Environ Int. 2022;158:107008.
Hyland C, Bradman A, Gerona R, Patton S, Zakharevich I, Gunier RB, et al. Organic diet intervention significantly reduces urinary pesticide levels in U.S. children and adults. Environ Res. 2019;171:568–75.
Curl CL, Meierotto L, Som Castellano RL. Understanding challenges to well-being among Latina FarmWorkers in rural Idaho using in an interdisciplinary, mixed-methods approach. Int J Environ Res Public Health. 2020;18:169.
Guo H, Yu X, Liu Z, Li J, Ye J, Zha Z. Deltamethrin transformation by bacillus thuringiensis and the associated metabolic pathways. Environ Int. 2020;145:106167.
Samsel A, Seneff S. Glyphosate’s suppression of cytochrome P450 enzymes and amino acid biosynthesis by the gut microbiome: pathways to modern diseases. Entropy. 2013;15:1416–63.
Mesnage R, Antoniou MN. Computational modelling provides insight into the effects of glyphosate on the shikimate pathway in the human gut microbiome. Curr Res Toxicol. 2020;1:25–33.
Velmurugan G, Ramprasath T, Swaminathan K, Mithieux G, Rajendhran J, Dhivakar M, et al. Gut microbial degradation of organophosphate insecticides-induces glucose intolerance via gluconeogenesis. Genome Biol. 2017;18:8.
Deziel NC, Friesen MC, Hoppin JA, Hines CJ, Thomas K, Freeman LEB. A review of nonoccupational pathways for pesticide exposure in women living in agricultural areas. Environ Health Perspect. 2015;123:515–24.
Vogel N, Conrad A, Apel P, Rucic E, Kolossa-Gehring M. Human biomonitoring reference values: differences and similarities between approaches for identifying unusually high exposure of pollutants in humans. Int J Hyg Environ Health. 2019;222:30–3.
Casals-Pascual C, González A, Vázquez-Baeza Y, Song SJ, Jiang L, Knight R. Microbial diversity in clinical microbiome studies: sample size and statistical power considerations. Gastroenterology. 2020;158:1524–8.
Knight R, Jansson J, Field D, Fierer N, Desai N, Fuhrman JA, et al. Unlocking the potential of metagenomics through replicated experimental design. Nat Biotechnol. 2012;30:513–20.
Cheung AC, Walker DI, Juran BD, Miller GW, Lazaridis KN. Studying the Exposome to understand the environmental determinants of complex liver diseases. Hepatology. 2020;71:352–62.
McLaren MR, Willis AD, Callahan BJ. Consistent and correctable bias in metagenomic sequencing experiments. Elife. 2019;8:e46923.
Costea PI, Zeller G, Sunagawa S, Pelletier E, Alberti A, Levenez F, et al. Towards standards for human fecal sample processing in metagenomic studies. Nat Biotechnol. 2017;35:1069–76.
Singer GAC, Fahner NA, Barnes JG, McCarthy A, Hajibabaei M. Comprehensive biodiversity analysis via ultra-deep patterned flow cell technology: a case study of eDNA metabarcoding seawater. Sci Rep. 2019;9:5991.
Rampelli S, Schnorr SL, Consolandi C, Turroni S, Severgnini M, Peano C, et al. Metagenome sequencing of the Hadza hunter-gatherer gut microbiota. Curr Biol. 2015;25:1682–93.
Jackson MA, Verdi S, Maxan ME, Shin CM, Zierer J, Bowyer RCE, et al. Gut microbiota associations with common diseases and prescription medications in a population-based cohort. Nat Commun. 2018;9:2655.
Vujkovic-Cvijin I, Sklar J, Jiang L, Natarajan L, Knight R, Belkaid Y. Host variables confound gut microbiota studies of human disease. Nature. 2020;587:448–54.
Bowyer RCE, Jackson MA, Le Roy CI, Ni Lochlainn M, Spector TD, Dowd JB, et al. Socioeconomic status and the gut microbiome: a TwinsUK cohort study. Microorganisms. 2019;7(1):17.
Ye SH, Siddle KJ, Park DJ, Sabeti PC. Benchmarking metagenomics tools for taxonomic classification. Cell. 2019;178:779–94.