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Cited by 40Parkinson's Disease Mechanisms and TreatmentsGut microbiota and healthPesticide Exposure and Toxicity

Pesticides and the Microbiome-Gut-Brain Axis: Convergent Pathways in the Pathogenesis of Parkinson’s Disease

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Kulcsarova, Kristina, Bang, Corinna, Berg, Daniela, Schaeffer, Eva·2023·Journal of Parkinson’s Disease
DOI 10.3233/jpd-230206PMC PMC10657696
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Abstract

The increasing global burden of Parkinson’s disease (PD), termed the PD pandemic, is exceeding expectations related purely to population aging and is likely driven in part by lifestyle changes and environmental factors. Pesticides are well recognized risk factors for PD, supported by both epidemiological and experimental evidence, with multiple detrimental effects beyond dopaminergic neuron damage alone. The microbiome-gut-brain axis has gained much attention in recent years and is considered to be a significant contributor and driver of PD pathogenesis. In this narrative review, we first focus on how both pesticides and the microbiome may influence PD initiation and progression independently, describing pesticide-related central and peripheral neurotoxicity and microbiome-related local and systemic effects due to dysbiosis and microbial metabolites. We then depict the bidirectional interplay between pesticides and the microbiome in the context of PD, synthesizing current knowledge about pesticide-induced dysbiosis, microbiome-mediated alterations in pesticide availability, metabolism and toxicity, and complex systemic pesticide-microbiome-host interactions related to inflammatory and metabolic pathways, insulin resistance and other mechanisms. An overview of the unknowns follows, and the role of pesticide-microbiome interactions in the proposed body-/brain-first phenotypes of PD, the complexity of environmental exposures and gene-environment interactions is discussed. The final part deals with possible further steps for translation, consisting of recommendations on future pesticide use and research as well as an outline of promising preventive/therapeutic approaches targeted on strengthening or restoring a healthy gut microbiome, closing with a summary of current gaps and future perspectives in the field.

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  • There is an increasing array of environmental factors being linked with PD and the microbiome, including pesticides like rotenone, paraquat, and glyphosate.

    “There is an increasing array of environmental factors being linked with PD and the microbiome, including pesticides like rotenone, paraquat, and glyphosate [192].”

    From The gut–brain axis in early Parkinson’s disease: from prodrome to prevention (2025) · cites this paper as [192]

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  1. [1]Poewe W, Seppi K, Tanner CM, Halliday GM, Brundin P, Volkmann J, Schrag A-E, Lang AE (2017) Parkinson disease. Nat Rev Dis Primer 3, 17013. 28332488
  2. [2]Pan L, Meng L, He M, Zhang Z (2021) Tau in the pathophysiology of Parkinson’s disease. J Mol Neurosci 71, 2179– 2191. 33459970 PMC8585831
  3. [3]Pan L, Li C, Meng L, Tian Y, He M, Yuan X, Zhang G, Zhang Z, Xiong J, Chen G, Zhang Z (2022) Tau accelerates α-synuclein aggregation and spreading in Parkinson’s disease. Brain 145, 3454– 3471. 35552614
  4. [4]Feigin VL, Abajobir AA, Abate KH, Abd-Allah F, Abdulle AM, Abera SF, Abyu GY, Ahmed MB, Aichour AN, Aichour I, et al. (2017) Global, regional, and national burden of neurological disorders during 1990–2015: A systematic analysis for the Global Burden of Disease Study 2015. Lancet Neurol 16, 877– 897. 28931491 PMC5641502
  5. [6]Ou Z, Pan J, Tang S, Duan D, Yu D, Nong H, Wang Z (2021) Global trends in the incidence, prevalence, and years lived with disability of Parkinson’s disease in 204 countries/territories from 1990 to 2019. Front Public Health 9, 776847. 34950630 PMC8688697
  6. [7]Dorsey ER, Sherer T, Okun MS, Bloem BR (2018) The emerging evidence of the Parkinson pandemic. J Parkinsons Dis 8, S3– S8. 30584159 PMC6311367
  7. [8]Allen L (2017) Are we facing a noncommunicable disease pandemic?. J Epidemiol Glob Health 7, 5– 9. 27886846 PMC7103919
  8. [10]Pezzoli G, Cereda E (2013) Exposure to pesticides or solvents and risk of Parkinson disease. Neurology 80, 2035– 2041. 23713084
  9. [11]Weisskopf MG, Weuve J, Nie H, Saint-Hilaire M-H, Sudarsky L, Simon DK, Hersh B, Schwartz J, Wright RO, Hu H (2010) Association of cumulative lead exposure with Parkinson’s disease. Environ Health Perspect 118, 1609– 1613. 20807691 PMC2974701
  10. [12]Goldman SM (2014) Environmental toxins and Parkinson’s disease. Annu Rev Pharmacol Toxicol 54, 141– 164. 24050700
  11. [13]Muthane UB, Ragothaman M, Gururaj G (2007) Epidemiology of Parkinson’s disease and movement disorders in India: Problems and possibilities. J Assoc Physicians India 55, 719– 724. 18173026
  12. [14]Azizova TV, Bannikova MV, Grigoryeva ES, Rybkina VL, Hamada N (2020) Occupational exposure to chronic ionizing radiation increases risk of Parkinson’s disease incidence in Russian Mayak workers. Int J Epidemiol 49, 435– 447. 31722376
  13. [15]Noyce AJ, Bestwick JP, Silveira-Moriyama L, Hawkes CH, Giovannoni G, Lees AJ, Schrag A (2012) Meta-analysis of early nonmotor features and risk factors for Parkinson disease. Ann Neurol 72, 893– 901. 23071076 PMC3556649
  14. [16]Gunnarsson L-G, Bodin L (2017) Parkinson’s disease and occupational exposures: A systematic literature review and meta-analyses. Scand J Work Environ Health 43, 197– 209. 28379585
  15. [17]Berg D, Postuma RB, Adler CH, Bloem BR, Chan P, Dubois B, Gasser T, Goetz CG, Halliday G, Joseph L, Lang AE, Liepelt-Scarfone I, Litvan I, Marek K, Obeso J, Oertel W, Olanow CW, Poewe W, Stern M, Deuschl G (2015) MDS research criteria for prodromal Parkinson’s disease. Mov Disord 30, 1600– 1611. 26474317
  16. [18]Heinzel S, Berg D, Gasser T, Chen H, Yao C, Postuma RB, MDS Task Force on the Definition of Parkinson’s Disease (2019) Update of the MDS research criteria for prodromal Parkinson’s disease. Mov Disord 34, 1464– 1470. 31412427
  17. [19]van der Mark M, Brouwer M, Kromhout H, Nijssen P, Huss A, Vermeulen R (2012) Is pesticide use related to Parkinson disease? Some clues to heterogeneity in study results. Environ Health Perspect 120, 340– 347. 22389202 PMC3295350
  18. [20]Van Maele-Fabry G, Hoet P, Vilain F, Lison D (2012) Occupational exposure to pesticides and Parkinson’s disease: A systematic review and meta-analysis of cohort studies. Environ Int 46, 30– 43. 22698719
  19. [21]Elbaz A, Moisan F (2016) The scientific bases to consider Parkinson’s disease an occupational disease in agriculture professionals exposed to pesticides in France. J Epidemiol Community Health 70, 319– 321. 26507749
  20. [23]Myung W, Lee G-H, Won H-H, Fava M, Mischoulon D, Nyer M, Kim DK, Heo J-Y, Jeon HJ (2015) Paraquat prohibition and change in the suicide rate and methods in South Korea. PLoS One 10, e0128980. 26035175 PMC4452788
  21. [24]Huang Y, Zhan H, Bhatt P, Chen S (2019) Paraquat degradation from contaminated environments: Current achievements and perspectives. Front Microbiol 10, 1754. 31428067 PMC6689968
  22. [25]Arotcarena M-L, Dovero S, Prigent A, Bourdenx M, Camus S, Porras G, Thiolat M-L, Tasselli M, Aubert P, Kruse N, Mollenhauer B, Trigo Damas I, Estrada C, Garcia-Carrillo N, Vaikath NN, El-Agnaf OMA, Herrero MT, Vila M, Obeso JA, Derkinderen P, Dehay B, Bezard E (2020) Bidirectional gut-to-brain and brain-to-gut propagation of synucleinopathy in non-human primates. Brain 143, 1462– 1475. 32380543
  23. [26]Ghaisas S, Maher J, Kanthasamy A (2016) Gut microbiome in health and disease: Linking the microbiome–gut–brain axis and environmental factors in the pathogenesis of systemic and neurodegenerative diseases. Pharmacol Ther 158, 52– 62. 26627987 PMC4747781
  24. [27]Carabotti M, Scirocco A, Maselli MA, Severi C (2015) The gut-brain axis: Interactions between enteric microbiota, central and enteric nervous systems. Ann Gastroenterol 28, 203– 209. 25830558 PMC4367209
  25. [28]Sun X, Xue L, Wang Z, Xie A (2022) Update to the treatment of Parkinson’s disease based on the gut-brain axis mechanism. Front Neurosci 16, 878239. 35873830 PMC9299103
  26. [29]Yuan X, Pan Z, Jin C, Ni Y, Fu Z, Jin Y (2019) Gut microbiota: An underestimated and unintended recipient for pesticide-induced toxicity. Chemosphere 227, 425– 434. 31003127
  27. [30]Sharma T, Sirpu Natesh N, Pothuraju R, Batra SK, Rachagani S (2023) Gut microbiota: A non-target victim of pesticide-induced toxicity. Gut Microbes 15, 2187578. 36919486 PMC10026936
  28. [31]Matsuzaki R, Gunnigle E, Geissen V, Clarke G, Nagpal J, Cryan JF (2023) Pesticide exposure and the microbiota-gut-brain axis. ISME J 17, 1153– 1166. 37328570 PMC10356795
  29. [32]Gois MFB, Fernández-Pato A, Huss A, Gacesa R, Wijmenga C, Weersma RK, Fu J, Vermeulen RCH, Zhernakova A, Lenters VC, Kurilshikov A (2023) Impact of occupational pesticide exposure on the human gut microbiome. Front Microbiol 14, 1223120. 37637104 PMC10448898
  30. [33]Langston JW, Ballard P, Tetrud JW, Irwin I (1983) Chronic Parkinsonism in humans due to a product of meperidine-analog synthesis. Science 219, 979– 980. 6823561
  31. [34]Cicchetti F, Drouin-Ouellet J, Gross RE (2009) Environmental toxins and Parkinson’s disease: What have we learned from pesticide-induced animal models? Trends Pharmacol Sci 30, 475– 483. 19729209
  32. [35]Markey SP, Johannessen JN, Chiueh CC, Burns RS, Herkenham MA (1984) Intraneuronal generation of a pyridinium metabolite may cause drug-induced parkinsonism. Nature 311, 464– 467. 6332988
  33. [36]Betarbet R, Sherer TB, MacKenzie G, Garcia-Osuna M, Panov AV, Greenamyre JT (2000) Chronic systemic pesticide exposure reproduces features of Parkinson’s disease. Nat Neurosci 3, 1301– 1306. 11100151
  34. [37]Cannon JR, Tapias V, Na HM, Honick AS, Drolet RE, Greenamyre JT (2009) A highly reproducible rotenone model of Parkinson’s disease. Neurobiol Dis 34, 279– 290. 19385059 PMC2757935
  35. [38]McCormack AL, Thiruchelvam M, Manning-Bog AB, Thiffault C, Langston JW, Cory-Slechta DA, Di Monte DA (2002) Environmental risk factors and Parkinson’s disease: Selective degeneration of nigral dopaminergic neurons caused by the herbicide paraquat. Neurobiol Dis 10, 119– 127. 12127150
  36. [39]Brooks AI, Chadwick CA, Gelbard HA, Cory-Slechta DA, Federoff HJ (1999) Paraquat elicited neurobehavioral syndrome caused by dopaminergic neuron loss. Brain Res 823, 1– 10. 10095006
  37. [40]Thiruchelvam M, Richfield EK, Baggs RB, Tank AW, Cory-Slechta DA (2000) The nigrostriatal dopaminergic system as a preferential target of repeated exposures to combined paraquat and maneb: Implications for Parkinson’s disease. J Neurosci 20, 9207– 9214. 11124998 PMC6773035
  38. [41]Hatcher JM, Richardson JR, Guillot TS, McCormack AL, Di Monte DA, Jones DP, Pennell KD, Miller GW (2007) Dieldrin exposure induces oxidative damage in the mouse nigrostriatal dopamine system. Exp Neurol 204, 619– 630. 17291500 PMC1896133
  39. [42]De Miranda BR, Goldman SM, Miller GW, Greenamyre JT, Dorsey ER (2022) Preventing Parkinson’s disease: An environmental agenda. J Parkinsons Dis 12, 45– 68. 34719434 PMC8842749
  40. [43]Wirdefeldt K, Adami H-O, Cole P, Trichopoulos D, Mandel J (2011) Epidemiology and etiology of Parkinson’s disease: A review of the evidence. Eur J Epidemiol 26, 1– 58. 21626386
  41. [44]Freire C, Koifman S (2012) Pesticide exposure and Parkinson’s disease: Epidemiological evidence of association. Neurotoxicology 33, 947– 971. 22627180
  42. [45]Yuan X, Tian Y, Liu C, Zhang Z (2022) Environmental factors in Parkinson’s disease: New insights into the molecular mechanisms. Toxicol Lett 356, 1– 10. 34864130
  43. [46]Vellingiri B, Chandrasekhar M, Sri Sabari S, Gopalakrishnan AV, Narayanasamy A, Venkatesan D, Iyer M, Kesari K, Dey A (2022) Neurotoxicity of pesticides –A link to neurodegeneration. Ecotoxicol Environ Saf 243, 113972. 36029574
  44. [47]Nabi M, Tabassum N (2022) Role of environmental toxicants on neurodegenerative disorders. Front Toxicol 4, 837579. 35647576 PMC9131020
  45. [48]Chaza C, Sopheak N, Mariam H, David D, Baghdad O, Moomen B (2018) Assessment of pesticide contamination in Akkar groundwater, northern Lebanon. Environ Sci Pollut Res 25, 14302– 14312. 28265872
  46. [49]Yuan Y, Shrestha S, Luo Z, Li C, Plassman BL, Parks CG, Hofmann JN, Beane Freeman LE, Sandler DP, Chen H (2022) High pesticide exposure events and dream-enacting behaviors among US farmers. Mov Disord 37, 962– 971. 35152487 PMC9524747
  47. [50]Bhatt MH, Elias MA, Mankodi AK (1999) Acute and reversible parkinsonism due to organophosphate pesticide intoxication: Five cases. Neurology 52, 1467– 1471. 10227636
  48. [51]McKnight S, Hack N (2020) Toxin-Induced Parkinsonism. Neurol Clin 38, 853– 865. 33040865
  49. [52]Weissbach A, Wittke C, Kasten M, Klein C (2019) “Atypical” Parkinson’s disease –genetic. Int Rev Neurobiol 149, 207– 235. 31779813
  50. [53]Gasser T (2015) Usefulness of genetic testing in PD and PD trials: A balanced review. J Parkinsons Dis 5, 209– 215. 25624421 PMC4923738
  51. [54]Eriguchi M, Iida K, Ikeda S, Osoegawa M, Nishioka K, Hattori N, Nagayama H, Hara H (2019) Parkinsonism relating to intoxication with glyphosate. Intern Med 58, 1935– 1938. 30799335 PMC6663540
  52. [55]Barbosa ER, Leiros da Costa MD, Bacheschi LA, Scaff M, Leite CC (2001) Parkinsonism after glycine-derivate exposure. Mov Disord 16, 565– 568. 11391760
  53. [56]Caballero M, Amiri S, Denney JT, Monsivais P, Hystad P, Amram O (2018) Estimated residential exposure to agricultural chemicals and premature mortality by Parkinson’s disease in Washington state. Int J Environ Res Public Health 15, 2885. 30558363 PMC6313412
  54. [57]Wang G, Fan X-N, Tan Y-Y, Cheng Q, Chen S-D (2011) Parkinsonism after chronic occupational exposure to glyphosate. Parkinsonism Relat Disord 17, 486– 487. 21367645
  55. [58]Paul KC, Krolewski RC, Lucumi Moreno E, Blank J, Holton KM, Ahfeldt T, Furlong M, Yu Y, Cockburn M, Thompson LK, Kreymerman A, Ricci-Blair EM, Li YJ, Patel HB, Lee RT, Bronstein J, Rubin LL, Khurana V, Ritz B (2023) A pesticide and iPSC dopaminergic neuron screen identifies and classifies Parkinson-relevant pesticides. Nat Commun 14, 2803. 37193692 PMC10188516
  56. [59]Saravanan KS, Sindhu KM, Mohanakumar KP (2005) Acute intranigral infusion of rotenone in rats causes progressive biochemical lesions in the striatum similar to Parkinson’s disease. Brain Res 1049, 147– 155. 15936733
  57. [60]Moretto A, Colosio C (2011) Biochemical and toxicological evidence of neurological effects of pesticides: The example of Parkinson’s disease. Neurotoxicology 32, 383– 391. 21402100
  58. [61]Arnold B, Cassady SJ, VanLaar VS, Berman SB (2011) Integrating multiple aspects of mitochondrial dynamics in neurons: Age-related differences and dynamic changes in a chronic rotenone model. Neurobiol Dis 41, 189– 200. 20850532 PMC3021420
  59. [63]Johnson ME, Bobrovskaya L (2015) An update on the rotenone models of Parkinson’s disease: Their ability to reproduce the features of clinical disease and model gene–environment interactions. NeuroToxicology 46, 101– 116. 25514659
  60. [64]Zeng X-S, Geng W-S, Jia J-J (2018) Neurotoxin-induced animal models of Parkinson disease: Pathogenic mechanism and assessment. ASN Neuro 10, 1759091418777438. 29809058 PMC5977437
  61. [65]Martella G, Madeo G, Maltese M, Vanni V, Puglisi F, Ferraro E, Schirinzi T, Valente EM, Bonanni L, Shen J, Mandolesi G, Mercuri NB, Bonsi P, Pisani A (2016) Exposure to low-dose rotenone precipitates synaptic plasticity alterations in PINK1 heterozygous knockout mice. Neurobiol Dis 91, 21– 36. 26916954
  62. [66]Wu F, Wang Z, Gu J-H, Ge J-B, Liang Z-Q, Qin Z-H (2013) p38MAPK/p53-Mediated Bax induction contributes to neurons degeneration in rotenone-induced cellular and rat models of Parkinson’s disease. Neurochem Int 63, 133– 140. 23714208
  63. [67]Feng J (2006) Microtubule: A common target for parkin and Parkinson’s disease toxin. Neuroscientist 12, 469– 476. 17079513
  64. [68]Mastroberardino PG, Hoffman EK, Horowitz MP, Betarbet R, Taylor G, Cheng D, Na HM, Gutekunst C-A, Gearing M, Trojanowski JQ, Anderson M, Chu CT, Peng J, Greenamyre JT (2009) A novel transferrin/TfR2-mediated mitochondrial iron transport system is disrupted in Parkinson’s disease. Neurobiol Dis 34, 417– 431. 19250966 PMC2784936
  65. [69]Ibarra-Gutiérrez MT, Serrano-García N, Orozco-Ibarra M (2023) Rotenone-induced model of Parkinson’s disease: Beyond mitochondrial complex I inhibition. Mol Neurobiol 60, 1929– 1948. 36593435
  66. [70]Lawana V, Cannon JR (2020) Chapter Five –Rotenone neurotoxicity: Relevance to Parkinson’s disease. In Advances in Neurotoxicology, Aschner M, Costa LG, eds. Academic Press, pp. 209–254.
  67. [71]Höglinger GU, Féger J, Prigent A, Michel PP, Parain K, Champy P, Ruberg M, Oertel WH, Hirsch EC (2003) Chronic systemic complex I inhibition induces a hypokinetic multisystem degeneration in rats. J Neurochem 84, 491– 502. 12558969
  68. [72]Elgayar SAM, Abdel-Hafez AAM, Gomaa AMS, Elsherif R (2018) Vulnerability of glia and vessels of rat substantia nigra in rotenone Parkinson model. Ultrastruct Pathol 42, 181– 192. 29466086
  69. [73]Kim S, Pajarillo E, Nyarko-Danquah I, Aschner M, Lee E (2023) Role of astrocytes in Parkinson’s disease associated with genetic mutations and neurotoxicants. Cells 12, 622. 36831289 PMC9953822
  70. [74]Gao H-M, Hong J-S, Zhang W, Liu B (2002) Distinct role for microglia in rotenone-induced degeneration of dopaminergic neurons. J Neurosci 22, 782– 790. 11826108 PMC6758500
  71. [75]Sherer TB, Betarbet R, Kim JH, Greenamyre JT (2003) Selective microglial activation in the rat rotenone model of Parkinson’s disease. Neurosci Lett 341, 87– 90. 12686372
  72. [76]Castello PR, Drechsel DA, Patel M (2007) Mitochondria are a major source of paraquat-induced reactive oxygen species production in the brain. J Biol Chem 282, 14186– 14193. 17389593 PMC3088512
  73. [77]Stojkovska I, Wagner BM, Morrison BE (2015) Parkinson’s disease and enhanced inflammatory response. Exp Biol Med 240, 1387– 1395. PMC4935292 25769314
  74. [78]Janda E, Lascala A, Carresi C, Parafati M, Aprigliano S, Russo V, Savoia C, Ziviani E, Musolino V, Morani F, Isidoro C, Mollace V (2015) Parkinsonian toxin-induced oxidative stress inhibits basal autophagy in astrocytes via NQO2/quinone oxidoreductase 2: Implications for neuroprotection. Autophagy 11, 1063– 1080. 26046590 PMC4590600
  75. [80]Wills J, Credle J, Oaks AW, Duka V, Lee J-H, Jones J, Sidhu A (2012) Paraquat, but not maneb, induces synucleinopathy and tauopathy in striata of mice through inhibition of proteasomal and autophagic pathways. PLoS One 7, e30745. 22292029 PMC3264632
  76. [81]Musgrove RE, Helwig M, Bae E-J, Aboutalebi H, Lee S-J, Ulusoy A, Monte DAD (2019) Oxidative stress in vagal neurons promotes parkinsonian pathology and intercellular α-synuclein transfer. J Clin Invest 129, 3738– 3753. 31194700 PMC6715407
  77. [82]Desplats P, Patel P, Kosberg K, Mante M, Patrick C, Rockenstein E, Fujita M, Hashimoto M, Masliah E (2012) Combined exposure to Maneb and Paraquat alters transcriptional regulation of neurogenesis-related genes in mice models of Parkinson’s disease. Mol Neurodegener 7, 49. 23017109 PMC3502617
  78. [83]Thrash B, Uthayathas S, Karuppagounder SS, Suppiramaniam V, Dhanasekaran M (2007) Paraquat and maneb induced neurotoxicity. Proc West Pharmacol Soc 50, 31– 42. 18605226
  79. [84]Zhang J, Fitsanakis VA, Gu G, Jing D, Ao M, Amarnath V, Montine TJ (2003) Manganese ethylene-bis-dithiocarbamate and selective dopaminergic neurodegeneration in rat: A link through mitochondrial dysfunction. J Neurochem 84, 336– 346. 12558996
  80. [85]Barlow BK, Cory-Slechta DA, Richfield EK, Thiruchelvam M (2007) The gestational environment and Parkinson’s disease: Evidence for neurodevelopmental origins of a neurodegenerative disorder. Reprod Toxicol 23, 457– 470. 17350799
  81. [86]Hou L, Zhang C, Wang K, Liu X, Wang H, Che Y, Sun F, Zhou X, Zhao X, Wang Q (2017) Paraquat and maneb co-exposure induces noradrenergic locus coeruleus neurodegeneration through NADPH oxidase-mediated microglial activation. Toxicology 380, 1– 10. 28202386
  82. [87]Madani NA, Carpenter DO (2022) Effects of glyphosate and glyphosate-based herbicides like RoundupTM on the mammalian nervous system: A review. Environ Res 214, 113933. 35868581
  83. [89]Martínez M-A, Ares I, Rodríguez J-L, Martínez M, Martínez-Larrañaga M-R, Anadón A (2018) Neurotransmitter changes in rat brain regions following glyphosate exposure. Environ Res 161, 212– 219. 29156344
  84. [91]Cattani D, Cesconetto PA, Tavares MK, Parisotto EB, De Oliveira PA, Rieg CEH, Leite MC, Prediger RDS, Wendt NC, Razzera G, Filho DW, Zamoner A (2017) Developmental exposure to glyphosate-based herbicide and depressive-like behavior in adult offspring: Implication of glutamate excitotoxicity and oxidative stress. Toxicology 387, 67– 80. 28627408
  85. [92]Gui Y, Fan X, Wang H, Wang G, Chen S (2012) Glyphosate induced cell death through apoptotic and autophagic mechanisms. Neurotoxicol Teratol 34, 344– 349. 22504123
  86. [93]Pu Y, Chang L, Qu Y, Wang S, Tan Y, Wang X, Zhang J, Hashimoto K (2020) Glyphosate exposure exacerbates the dopaminergic neurotoxicity in the mouse brain after repeated administration of MPTP. Neurosci Lett 730, 135032. 32387710
  87. [94]Saeedi Saravi SS, Dehpour AR (2016) Potential role of organochlorine pesticides in the pathogenesis of neurodevelopmental, neurodegenerative, and neurobehavioral disorders: A review. Life Sci 145, 255– 264. 26549647
  88. [95]Pessah IN, Lein PJ, Seegal RF, Sagiv SK (2019) Neurotoxicity of polychlorinated biphenyls and related organohalogens. Acta Neuropathol (Berl) 138, 363– 387. 30976975 PMC6708608
  89. [96]Kanthasamy AG, Kitazawa M, Kanthasamy A, Anantharam V (2005) Dieldrin-induced neurotoxicity: Relevance to Parkinson’s disease pathogenesis. Neurotoxicology 26, 701– 719. 16112328
  90. [97]Sun F, Anantharam V, Latchoumycandane C, Kanthasamy A, Kanthasamy AG (2005) Dieldrin induces ubiquitin-proteasome dysfunction in α-synuclein overexpressing dopaminergic neuronal cells and enhances susceptibility to apoptotic cell death. J Pharmacol Exp Ther 315, 69– 79. 15987830
  91. [98]Song C, Kanthasamy A, Anantharam V, Sun F, Kanthasamy AG (2010) Environmental neurotoxic pesticide increases histone acetylation to promote apoptosis in dopaminergic neuronal cells: Relevance to epigenetic mechanisms of neurodegeneration. Mol Pharmacol 77, 621– 632. 20097775 PMC2847769
  92. [99]Kochmanski J, VanOeveren SE, Patterson JR, Bernstein AI (2019) Developmental dieldrin exposure alters DNA methylation at genes related to dopaminergic neuron development and Parkinson’s disease in mouse midbrain. Toxicol Sci 169, 593– 607. 30859219 PMC6542339
  93. [100]Gasmi S, Rouabhi R, Kebieche M, Boussekine S, Salmi A, Toualbia N, Taib C, Bouteraa Z, Chenikher H, Henine S, Djabri B (2017) Effects of Deltamethrin on striatum and hippocampus mitochondrial integrity and the protective role of Quercetin in rats. Environ Sci Pollut Res 24, 16440– 16457. 28551743
  94. [101]Mohammadi H, Ghassemi-Barghi N, Malakshah O, Ashari S (2019) Pyrethroid exposure and neurotoxicity: A mechanistic approach. Arh Hig Rada Toksikol 70, 74– 89. 31246571
  95. [102]Wan F, Yu T, Hu J, Yin S, Li Y, Kou L, Chi X, Wu J, Sun Y, Zhou Q, Zou W, Zhang Z, Wang T (2022) The pyrethroids metabolite 3-phenoxybenzoic acid induces dopaminergic degeneration. Sci Total Environ 838, 156027. 35605864
  96. [103]Costa LG (2015) The neurotoxicity of organochlorine and pyrethroid pesticides. Handb Clin Neurol 131, 135– 148. 26563787
  97. [104]Travagli RA, Browning KN, Camilleri M (2020) Parkinson disease and the gut: New insights into pathogenesis and clinical relevance. Nat Rev Gastroenterol Hepatol 17, 673– 685. 32737460
  98. [105]Anselmi L, Toti L, Bove C, Hampton J, Travagli RA (2017) A nigro-vagal pathway controls gastric motility and is affected in a rat model of parkinsonism. Gastroenterology 153, 1581– 1593. 28912019 PMC5705565
  99. [106]Drolet RE, Cannon JR, Montero L, Greenamyre JT (2009) Chronic rotenone exposure reproduces Parkinson’s disease gastrointestinal neuropathology. Neurobiol Dis 36, 96– 102. 19595768
  100. [107]Perez-Pardo P, Dodiya HB, Broersen LM, Douna H, van Wijk N, Lopes da Silva S, Garssen J, Keshavarzian A, Kraneveld AD (2018) Gut-brain and brain-gut axis in Parkinson’s disease models: Effects of a uridine and fish oil diet. Nutr Neurosci 21, 391– 402. 28276272
  101. [108]Cannon JR, Greenamyre JT (2010) Neurotoxic in vivo models of Parkinson’s disease recent advances. Prog Brain Res 184, 17– 33. 20887868
  102. [109]Greene JG, Noorian AR, Srinivasan S (2009) Delayed gastric emptying and enteric nervous system dysfunction in the rotenone model of Parkinson’s disease. Exp Neurol 218, 154– 161. 19409896 PMC2696567
  103. [110]Tasselli M, Chaumette T, Paillusson S, Monnet Y, Lafoux A, Huchet-Cadiou C, Aubert P, Hunot S, Derkinderen P, Neunlist M (2013) Effects of oral administration of rotenone on gastrointestinal functions in mice. Neurogastroenterol Motil 25, e183– 193. 23281940
  104. [113]Benvenuti L, D’Antongiovanni V, Pellegrini C, Antonioli L, Bernardini N, Blandizzi C, Fornai M (2020) Enteric glia at the crossroads between intestinal immune system and epithelial barrier: Implications for Parkinson disease. Int J Mol Sci 21, 9199. 33276665 PMC7730281
  105. [114]Sherer TB, Richardson JR, Testa CM, Seo BB, Panov AV, Yagi T, Matsuno-Yagi A, Miller GW, Greenamyre JT (2007) Mechanism of toxicity of pesticides acting at complex I: Relevance to environmental etiologies of Parkinson’s disease. J Neurochem 100, 1469– 1479. 17241123 PMC8669833
  106. [115]Palanisamy BN, Sarkar S, Malovic E, Samidurai M, Charli A, Zenitsky G, Jin H, Anantharam V, Kanthasamy A, Kanthasamy AG (2022) Environmental neurotoxic pesticide exposure induces gut inflammation and enteric neuronal degeneration by impairing enteric glial mitochondrial function in pesticide models of Parkinson’s disease: Potential relevance to gut-brain axis inflammation in Parkinson’s disease pathogenesis. Int J Biochem Cell Biol 147, 106225. 35550926 PMC10411482
  107. [116]Naudet N, Antier E, Gaillard D, Morignat E, Lakhdar L, Baron T, Bencsik A (2017) Oral exposure to paraquat triggers earlier expression of phosphorylated α-synuclein in the enteric nervous system of A53T mutant human α-synuclein transgenic mice. J Neuropathol Exp Neurol 76, 1046– 1057. 29040593 PMC5939863
  108. [117]Bove C, Coleman FH, Travagli RA (2019) Characterization of the basic membrane properties of neurons of the rat dorsal motor nucleus of the vagus in paraquat-induced models of parkinsonism. Neuroscience 418, 122– 132. 31491501 PMC6878173
  109. [118]Bove C, Anselmi L, Travagli RA (2019) Altered gastric tone and motility response to brain-stem dopamine in a rat model of parkinsonism. Am J Physiol Gastrointest Liver Physiol 317, G1– G7. 31042398 PMC6689734
  110. [119]Wang KD, Zhang BY, Zhang BF, Huang M (2022) Preliminary study on time-dependent changes of intestinal tract and brain-gut axis in mice model of Parkinson’s disease induced by paraquat. Chin J Ind Hyg Occup Dis 40, 161– 169. 35439855
  111. [120]Rueda-Ruzafa L, Cruz F, Roman P, Cardona D (2019) Gut microbiota and neurological effects of glyphosate. Neurotoxicology 75, 1– 8. 31442459
  112. [121]Palus K, Bulc M, Całka J (2022) Glyphosate affects the neurochemical phenotype of the intramural neurons in the duodenum in the pig. Neurogastroenterol Motil 35, e14507. 36502523
  113. [122]Braak H, Rüb U, Gai WP, Del Tredici K (2003) Idiopathic Parkinson’s disease: Possible routes by which vulnerable neuronal types may be subject to neuroinvasion by an unknown pathogen. J Neural Transm 110, 517– 536. 12721813
  114. [124]Pont-Sunyer C, Hotter A, Gaig C, Seppi K, Compta Y, Katzenschlager R, Mas N, Hofeneder D, Brücke T, Bayés A, Wenzel K, Infante J, Zach H, Pirker W, Posada IJ, Álvarez R, Ispierto L, De Fàbregues O, Callén A, Palasí A, Aguilar M, Martí MJ, Valldeoriola F, Salamero M, Poewe W, Tolosa E (2015) The onset of nonmotor symptoms in Parkinson’s disease (the ONSET PD study). Mov Disord 30, 229– 237. 25449044
  115. [126]Challis C, Hori A, Sampson TR, Yoo BB, Challis RC, Hamilton AM, Mazmanian SK, Volpicelli-Daley LA, Gradinaru V (2020) Gut-seeded α-synuclein fibrils promote gut dysfunction and brain pathology specifically in aged mice. Nat Neurosci 23, 327– 336. 32066981 PMC7065967
  116. [127]Stokholm MG, Danielsen EH, Hamilton-Dutoit SJ, Borghammer P (2016) Pathological α-synuclein in gastrointestinal tissues from prodromal Parkinson disease patients. Ann Neurol 79, 940– 949. 27015771
  117. [128]Bu J, Liu J, Liu K, Wang Z (2019) Diagnostic utility of gut α-synuclein in Parkinson’s disease: A systematic review and meta-analysis. Behav Brain Res 364, 340– 347. 30802532
  118. [129]Schaeffer E, Kluge A, Böttner M, Zunke F, Cossais F, Berg D, Arnold P (2020) Alpha synuclein connects the gut-brain axis in Parkinson’s disease patients –a view on clinical aspects, cellular pathology and analytical methodology. Front Cell Dev Biol 8, 573696. 33015066 PMC7509446
  119. [130]Braak H, Del Tredici K (2008) Invited Article: Nervous system pathology in sporadic Parkinson disease. Neurology 70, 1916– 1925. 18474848
  120. [131]Hawkes CH, Del Tredici K, Braak H (2009) Parkinson’s disease: The dual hit theory revisited. Ann N Y Acad Sci 1170, 615– 622. 19686202
  121. [132]Borghammer P, Van Den Berge N (2019) Brain-first versus gut-first Parkinson’s disease: A hypothesis. J Parkinsons Dis 9, S281– S295. 31498132 PMC6839496
  122. [133]Borghammer P (2021) The α-synuclein origin and connectome model (SOC Model) of Parkinson’s disease: Explaining motor asymmetry, non-motor phenotypes, and cognitive decline. J Parkinsons Dis 11, 455– 474. 33682732 PMC8150555
  123. [134]Sampson TR (2022) Introduction: Unraveling the complex contributions of indigenous microbes to neurological health and disease. Int Rev Neurobiol 167 xi– xvi. 36427961
  124. [135]Heintz-Buschart A, Wilmes P (2018) Human gut microbiome: Function matters. Trends Microbiol 26, 563– 574. 29173869
  125. [136]Ma Q, Xing C, Long W, Wang HY, Liu Q, Wang R-F (2019) Impact of microbiota on central nervous system and neurological diseases: The gut-brain axis. J Neuroinflammation 16, 53. 30823925 PMC6397457
  126. [137]Suganya K, Koo B-S (2020) Gut-brain axis: Role of gut microbiota on neurological disorders and how probiotics/prebiotics beneficially modulate microbial and immune pathways to improve brain functions. Int J Mol Sci 21, E7551. PMC7589356 33066156
  127. [138]Gubert C, Gasparotto J, Morais LH (2022) Convergent pathways of the gut microbiota–brain axis and neurodegenerative disorders. Gastroenterol Rep 10, goac017. PMC9109005 35582476
  128. [141]Ryman S, Vakhtin AA, Richardson SP, Lin HC (2023) Microbiome-gut-brain dysfunction in prodromal and symptomatic Lewy body diseases. J Neurol 270, 746– 758. 36355185 PMC9886597
  129. [142]Schwiertz A, Spiegel J, Dillmann U, Grundmann D, Bürmann J, Faßbender K, Schäfer K-H, Unger MM (2018) Fecal markers of intestinal inflammation and intestinal permeability are elevated in Parkinson’s disease. Parkinsonism Relat Disord 50, 104– 107. 29454662
  130. [143]Houser MC, Chang J, Factor SA, Molho ES, Zabetian CP, Hill-Burns EM, Payami H, Hertzberg VS, Tansey MG (2018) Stool immune profiles evince gastrointestinal inflammation in Parkinson’s disease. Mov Disord 33, 793– 804. 29572994 PMC5992021
  131. [145]Caputi V, Giron MC (2018) Microbiome-gut-brain axis and toll-like receptors in Parkinson’s disease. Int J Mol Sci 19, 1689. 29882798 PMC6032048
  132. [146]Burgueño JF, Abreu MT (2020) Epithelial Toll-like receptors and their role in gut homeostasis and disease. Nat Rev Gastroenterol Hepatol 17, 263– 278. 32103203
  133. [149]Clairembault T, Kamphuis W, Leclair-Visonneau L, Rolli-Derkinderen M, Coron E, Neunlist M, Hol EM, Derkinderen P (2014) Enteric GFAP expression and phosphorylation in Parkinson’s disease. J Neurochem 130, 805– 815. 24749759
  134. [150]Hor JW, Lim S-Y, Khor ES, Chong KK, Song SL, Ibrahim NM, Teh CSJ, Chong CW, Hilmi IN, Tan AH (2022) Fecal calprotectin in Parkinson’s disease and multiple system atrophy. J Mov Disord 15, 106– 114. 34937162 PMC9171316
  135. [151]Stolzenberg E, Berry D, Yang D, Lee EY, Kroemer A, Kaufman S, Wong GCL, Oppenheim JJ, Sen S, Fishbein T, Bax A, Harris B, Barbut D, Zasloff MA (2017) A role for neuronal alpha-synuclein in gastrointestinal immunity. J Innate Immun 9, 456– 463. 28651250 PMC5865636
  136. [153]Forsyth CB, Shannon KM, Kordower JH, Voigt RM, Shaikh M, Jaglin JA, Estes JD, Dodiya HB, Keshavarzian A (2011) Increased intestinal permeability correlates with sigmoid mucosa alpha-synuclein staining and endotoxin exposure markers in early Parkinson’s disease. PloS One 6, e28032. 22145021 PMC3228722
  137. [157]Resnikoff H, Metzger JM, Lopez M, Bondarenko V, Mejia A, Simmons HA, Emborg ME (2019) Colonic inflammation affects myenteric alpha-synuclein in nonhuman primates. J Inflamm Res 12, 113– 126. 31123415 PMC6511240
  138. [160]Tan E-K, Chao Y-X, West A, Chan L-L, Poewe W, Jankovic J (2020) Parkinson disease and the immune system –associations, mechanisms and therapeutics. Nat Rev Neurol 16, 303– 318. 32332985
  139. [163]Sampson TR, Debelius JW, Thron T, Janssen S, Shastri GG, Ilhan ZE, Challis C, Schretter CE, Rocha S, Gradinaru V, Chesselet M-F, Keshavarzian A, Shannon KM, Krajmalnik-Brown R, Wittung-Stafshede P, Knight R, Mazmanian SK (2016) Gut microbiota regulate motor deficits and neuroinflammation in a model of Parkinson’s disease. Cell 167, 1469– 1480.e12. 27912057 PMC5718049
  140. [164]Matheoud D, Cannon T, Voisin A, Penttinen A-M, Ramet L, Fahmy AM, Ducrot C, Laplante A, Bourque M-J, Zhu L, Cayrol R, Le Campion A, McBride HM, Gruenheid S, Trudeau L-E, Desjardins M (2019) Intestinal infection triggers Parkinson’s disease-like symptoms in Pink1-/- mice. Nature 571, 565– 569. 31316206
  141. [165]Houser MC, Tansey MG (2017) The gut-brain axis: Is intestinal inflammation a silent driver of Parkinson’s disease pathogenesis? NPJ Parkinsons Dis 3, 3. 28649603 PMC5445611
  142. [166]Groh KJ, Geueke B, Muncke J (2017) Food contact materials and gut health: Implications for toxicity assessment and relevance of high molecular weight migrants. Food Chem Toxicol 109, 1– 18. 28830834
  143. [167]Gillois K, Lévêque M, Théodorou V, Robert H, Mercier-Bonin M (2018) Mucus: An underestimated gut target for environmental pollutants and food additives. Microorganisms 6, 53. 29914144 PMC6027178
  144. [168]Zhang Y, Jin C, Wang X, Shen M, Zhou J, Wu S, Fu Z, Jin Y (2019) Propamocarb exposure decreases the secretion of neurotransmitters and causes behavioral impairments in mice. Environ Toxicol 34, 22– 29. 30251769
  145. [171]Bhattarai Y, Si J, Pu M, Ross OA, McLean PJ, Till L, Moor W, Grover M, Kandimalla KK, Margolis KG, Farrugia G, Kashyap PC (2021) Role of gut microbiota in regulating gastrointestinal dysfunction and motor symptoms in a mouse model of Parkinson’s disease. Gut Microbes 13, 1866974. 33459114 PMC7833732
  146. [172]Barichella M, Severgnini M, Cilia R, Cassani E, Bolliri C, Caronni S, Ferri V, Cancello R, Ceccarani C, Faierman S, Pinelli G, De Bellis G, Zecca L, Cereda E, Consolandi C, Pezzoli G (2019) Unraveling gut microbiota in Parkinson’s disease and atypical parkinsonism. Mov Disord 34, 396– 405. 30576008
  147. [174]Hasegawa S, Goto S, Tsuji H, Okuno T, Asahara T, Nomoto K, Shibata A, Fujisawa Y, Minato T, Okamoto A, Ohno K, Hirayama M (2015) intestinal dysbiosis and lowered serum lipopolysaccharide-binding protein in Parkinson’s disease. PloS One 10, e0142164. 26539989 PMC4634857
  148. [176]Hopfner F, Künstner A, Müller SH, Künzel S, Zeuner KE, Margraf NG, Deuschl G, Baines JF, Kuhlenbäumer G (2017) Gut microbiota in Parkinson disease in a northern German cohort. Brain Res 1667, 41– 45. 28506555
  149. [178]Bedarf JR, Hildebrand F, Coelho LP, Sunagawa S, Bahram M, Goeser F, Bork P, Wüllner U (2017) Functional implications of microbial and viral gut metagenome changes in early stage L-DOPA-naïve Parkinson’s disease patients. Genome Med 9, 39. 28449715 PMC5408370
  150. [180]Queipo-Ortuño MI, Seoane LM, Murri M, Pardo M, Gomez-Zumaquero JM, Cardona F, Casanueva F, Tinahones FJ (2013) Gut microbiota composition in male rat models under different nutritional status and physical activity and its association with serum leptin and ghrelin levels. PloS One 8, e65465. 23724144 PMC3665787
  151. [181]Bayliss JA, Lemus MB, Stark R, Santos VV, Thompson A, Rees DJ, Galic S, Elsworth JD, Kemp BE, Davies JS, Andrews ZB (2016) Ghrelin-AMPK signaling mediates the neuroprotective effects of calorie restriction in Parkinson’s disease. J Neurosci 36, 3049– 3063. 26961958 PMC4783502
  152. [182]Wang K, Zhang C, Zhang B, Li G, Shi G, Cai Q, Huang M (2022) Gut dysfunction may be the source of pathological aggregation of alpha-synuclein in the central nervous system through Paraquat exposure in mice. Ecotoxicol Environ Saf 246, 114152. 36201918
  153. [183]Li Y, Zuo Z, Zhang B, Luo H, Song B, Zhou Z, Chang X (2022) Impacts of early-life paraquat exposure on gut microbiota and body weight in adult mice. Chemosphere 291, 133135. 34863722
  154. [184]Souza da APS, Barros WMA, Silva JML, Silva MRM, Silva ABJ, Fernandes de MSS, dos Santos MERA, da Silva ML, do Carmo TS, Silva RKP, da Silva KG, de Souza SL, Souza de VON (2021) Effect of metabolic syndrome on Parkinson’s disease: A systematic review. Clinics 76, e3379. 34909941 PMC8634740
  155. [185]Schönbrunn E, Eschenburg S, Shuttleworth WA, Schloss JV, Amrhein N, Evans JNS, Kabsch W (2001) Interaction of the herbicide glyphosate with its target enzyme 5-enolpyruvylshikimate 3-phosphate synthase in atomic detail. Proc Natl Acad Sci U S A 98, 1376– 1380. 11171958 PMC29264
  156. [186]Leino L, Tall T, Helander M, Saloniemi I, Saikkonen K, Ruuskanen S, Puigbò P (2021) Classification of the glyphosate target enzyme (5-enolpyruvylshikimate-3-phosphate synthase) for assessing sensitivity of organisms to the herbicide. J Hazard Mater 408, 124556. 33243645
  157. [187]Mesnage R, Teixeira M, Mandrioli D, Falcioni L, Ducarmon QR, Zwittink RD, Mazzacuva F, Caldwell A, Halket J, Amiel C, Panoff J-M, Belpoggi F, Antoniou MN (2021) 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 129, 017005. 33502259 PMC7839352
  158. [188]Aitbali Y, Ba-M’hamed S, Elhidar N, Nafis A, Soraa N, Bennis M (2018) Glyphosate based- herbicide exposure affects gut microbiota, anxiety and depression-like behaviors in mice. Neurotoxicol Teratol 67, 44– 49. 29635013
  159. [189]Lozano VL, Defarge N, Rocque L-M, Mesnage R, Hennequin D, Cassier R, de Vendômois JS, Panoff J-M, Séralini G-E, Amiel C (2018) Sex-dependent impact of Roundup on the rat gut microbiome. Toxicol Rep 5, 96– 107. 29854581 PMC5977165
  160. [190]Mao Q, Manservisi F, Panzacchi S, Mandrioli D, Menghetti I, Vornoli A, Bua L, Falcioni L, Lesseur C, Chen J, Belpoggi F, Hu J (2018) 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 17, 50. 29843725 PMC5972442
  161. [191]Motta EVS, Raymann K, Moran NA (2018) Glyphosate perturbs the gut microbiota of honey bees. Proc Natl Acad Sci U S A 115, 10305– 10310. 30249635 PMC6187125
  162. [192]Shehata AA, Schrödl W, Aldin Alaa A, Hafez HM, Krüger M (2013) The effect of glyphosate on potential pathogens and beneficial members of poultry microbiota in vitro. Curr Microbiol 66, 350– 358. 23224412
  163. [193]Ackermann W, Coenen M, Schrödl W, Shehata AA, Krüger M (2015) The influence of glyphosate on the microbiota and production of botulinum neurotoxin during ruminal fermentation. Curr Microbiol 70, 374– 382. 25407376
  164. [194]Riede S, Toboldt A, Breves G, Metzner M, Köhler B, Bräunig J, Schafft H, Lahrssen-Wiederholt M, Niemann L (2016) Investigations on the possible impact of a glyphosate-containing herbicide on ruminal metabolism and bacteria in vitro by means of the ‘Rumen Simulation Technique.’. J Appl Microbiol 121, 644– 656. 27230806
  165. [195]Krüger M, Shehata AA, Schrödl W, Rodloff A (2013) Glyphosate suppresses the antagonistic effect of Enterococcus spp. on Clostridium botulinum. Anaerobe 20, 74– 78. 23396248
  166. [196]You M-J, Shin G-W, Lee C-S (2015) Clostridium tertium bacteremia in a patient with glyphosate ingestion. Am J Case Rep 16, 4– 7. 25577783 PMC4289481
  167. [197]Mesnage R, Antoniou MN (2020) Computational modelling provides insight into the effects of glyphosate on the shikimate pathway in the human gut microbiome. Curr Res Toxicol 1, 25– 33. 34345834 PMC8320642
  168. [199]Sampson TR, Mazmanian SK (2015) Control of brain development, function, and behavior by the microbiome. Cell Host Microbe 17, 565– 576. 25974299 PMC4442490
  169. [200]Fukumoto S, Tatewaki M, Yamada T, Fujimiya M, Mantyh C, Voss M, Eubanks S, Harris M, Pappas TN, Takahashi T (2003) Short-chain fatty acids stimulate colonic transit via intraluminal 5-HT release in rats. Am J Physiol-Regul Integr Comp Physiol 284, R1269– R1276. 12676748
  170. [201]Yano JM, Yu K, Donaldson GP, Shastri GG, Ann P, Ma L, Nagler CR, Ismagilov RF, Mazmanian SK, Hsiao EY (2015) Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis. Cell 161, 264– 276. 25860609 PMC4393509
  171. [202]O’Mahony SM, Marchesi JR, Scully P, Codling C, Ceolho A-M, Quigley EMM, Cryan JF, Dinan TG (2009) Early life stress alters behavior, immunity, and microbiota in rats: Implications for irritable bowel syndrome and psychiatric illnesses. Biol Psychiatry 65, 263– 267. 18723164
  172. [203]Pu Y, Yang J, Chang L, Qu Y, Wang S, Zhang K, Xiong Z, Zhang J, Tan Y, Wang X, Fujita Y, Ishima T, Wan D, Hwang SH, Hammock BD, Hashimoto K (2020) Maternal glyphosate exposure causes autism-like behaviors in offspring through increased expression of soluble epoxide hydrolase. Proc Natl Acad Sci U S A 117, 11753– 11759. 32398374 PMC7260984
  173. [204]Halliday GM, Leverenz JB, Schneider JS, Adler CH (2014) The neurobiological basis of cognitive impairment in Parkinson’s disease. Mov Disord 29, 634– 650. 24757112 PMC4049032
  174. [205]Chikatimalla R, Dasaradhan T, Koneti J, Cherukuri SP, Kalluru R, Gadde S (2022) Depression in Parkinson’s disease: A narrative review. Cureus 14, e27750. 36106206 PMC9447473
  175. [206]Perl DP, Olanow CW (2007) The neuropathology of manganese-induced Parkinsonism. J Neuropathol Exp Neurol 66, 675– 682. 17882011
  176. [207]Olanow CW (2004) Manganese-induced parkinsonism and Parkinson’s disease. Ann N Y Acad Sci 1012, 209– 223. 15105268
  177. [208]Lucchini RG, Martin CJ, Doney BC (2009) From manganism to manganese-induced parkinsonism: A conceptual model based on the evolution of exposure. Neuromolecular Med 11, 311– 321. 20012385 PMC12409775
  178. [209]Levy BS, Nassetta WJ (2003) Neurologic effects of manganese in humans: A review. Int J Occup Environ Health 9, 153– 163. 12848244
  179. [210]Willis AW, Evanoff BA, Lian M, Galarza A, Wegrzyn A, Schootman M, Racette BA (2010) Metal emissions and urban incident Parkinson disease: A community health study of Medicare beneficiaries by using geographic information systems. Am J Epidemiol 172, 1357– 1363. 20959505 PMC2998201
  180. [211]Samsel A, Seneff S (2015) Glyphosate, pathways to modern diseases III: Manganese, neurological diseases, and associated pathologies. Surg Neurol Int 6, 45. 25883837 PMC4392553
  181. [212]Archibald FS, Fridovich I (1981) Manganese, superoxide dismutase, and oxygen tolerance in some lactic acid bacteria. J Bacteriol 146, 928– 936. 6263860 PMC216946
  182. [213]Terkelsen MH, Hvingelby VS, Pavese N (2022) Molecular imaging of the GABAergic system in Parkinson’s disease and atypical parkinsonisms. Curr Neurol Neurosci Rep 22, 867– 879. 36400877 PMC9750911
  183. [214]Tette F-M, Kwofie SK, Wilson MD (2022) Therapeutic anti-depressant potential of microbial GABA produced by Lactobacillus rhamnosus strains for GABAergic signaling restoration and inhibition of addiction-induced HPA axis hyperactivity. Curr Issues Mol Biol 44, 1434– 1451. 35723354 PMC9164062
  184. [215]Finley JW, Davis CD (1999) Manganese deficiency and toxicity: Are high or low dietary amounts of manganese cause for concern? Biofactors 10, 15– 24. 10475586
  185. [216]Samsel A, Seneff S (2013) Glyphosate, pathways to modern diseases II: Celiac sprue and gluten intolerance. Interdiscip Toxicol 6, 159– 184. 24678255 PMC3945755
  186. [217]Ke T, Sidoryk-Wegrzynowicz M, Pajarillo E, Rizor A, Soares FAA, Lee E, Aschner M (2019) Role of astrocytes in manganese neurotoxicity revisited. Neurochem Res 44, 2449– 2459. 31571097 PMC7757856
  187. [218]Lindquist NG, Larsson BS, Lydén-Sokolowski A (1987) Neuromelanin and its possible protective and destructive properties. Pigment Cell Res 1, 133– 136. 3334086
  188. [219]Faria MA (2015) Glyphosate, neurological diseases –and the scientific method. Surg Neurol Int 6, 132. 26322242 PMC4538578
  189. [220]Peillex C, Pelletier M (2020) The impact and toxicity of glyphosate and glyphosate-based herbicides on health and immunity. J Immunotoxicol 17, 163– 174. 32897110
  190. [222]Lai F, Jiang R, Xie W, Liu X, Tang Y, Xiao H, Gao J, Jia Y, Bai Q (2018) Intestinal pathology and gut microbiota alterations in a methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson’s disease. Neurochem Res 43, 1986– 1999. 30171422
  191. [223]Xie W, Gao J, Jiang R, Liu X, Lai F, Tang Y, Xiao H, Jia Y, Bai Q (2020) Twice subacute MPTP administrations induced time-dependent dopaminergic neurodegeneration and inflammation in midbrain and ileum, as well as gut microbiota disorders in PD mice. Neurotoxicology 76, 200– 212. 31790727
  192. [224]Sun M-F, Zhu Y-L, Zhou Z-L, Jia X-B, Xu Y-D, Yang Q, Cui C, Shen Y-Q (2018) Neuroprotective effects of fecal microbiota transplantation on MPTP-induced Parkinson’s disease mice: Gut microbiota, glial reaction and TLR4/TNF-α signaling pathway. Brain Behav Immun 70, 48– 60. 29471030
  193. [225]Unger MM, Spiegel J, Dillmann K-U, Grundmann D, Philippeit H, Bürmann J, Faßbender K, Schwiertz A, Schäfer K-H (2016) Short chain fatty acids and gut microbiota differ between patients with Parkinson’s disease and age-matched controls. Parkinsonism Relat Disord 32, 66– 72. 27591074
  194. [226]Joly Condette C, Bach V, Mayeur C, Gay-Quéheillard J, Khorsi-Cauet H (2015) Chlorpyrifos exposure during perinatal period affects intestinal microbiota associated with delay of maturation of digestive tract in rats. J Pediatr Gastroenterol Nutr 61, 30– 40. 25643018
  195. [227]Nasuti C, Coman MM, Olek RA, Fiorini D, Verdenelli MC, Cecchini C, Silvi S, Fedeli D, Gabbianelli R (2016) Changes on fecal microbiota in rats exposed to permethrin during postnatal development. Environ Sci Pollut Res 23, 10930– 10937. 26898931
  196. [228]Reygner J, Joly Condette C, Bruneau A, Delanaud S, Rhazi L, Depeint F, Abdennebi-Najar L, Bach V, Mayeur C, Khorsi-Cauet H (2016) Changes in composition and function of human intestinal microbiota exposed to chlorpyrifos in oil as assessed by the SHIME® model. Int J Environ Res Public Health 13, 1088. 27827942 PMC5129298
  197. [229]Iszatt N, Janssen S, Lenters V, Dahl C, Stigum H, Knight R, Mandal S, Peddada S, González A, Midtvedt T, Eggesbø M (2019) Environmental toxicants in breast milk of Norwegian mothers and gut bacteria composition and metabolites in their infants at 1 month. Microbiome 7, 34. 30813950 PMC6393990
  198. [230]Caricilli AM, Castoldi A, Câmara NOS (2014) Intestinal barrier: A gentlemen’s agreement between microbiota and immunity. World J Gastrointest Pathophysiol 5, 18– 32. 24891972 PMC4024517
  199. [231]Ivanov II, Honda K (2012) Intestinal commensal microbes as immune modulators. Cell Host Microbe 12, 496– 508. 23084918 PMC3516493
  200. [232]Nishio J, Honda K (2012) Immunoregulation by the gut microbiota. Cell Mol Life Sci 69, 3635– 3650. 22527722 PMC11114866

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Authors
Kulcsarova, K., Bang, C., Berg, D., & Schaeffer, E.
Affiliations
  • Department of Neurology, P. J. Safarik University, Kosice, Slovak Republic
  • Christian-Albrechts-Universität zu Kiel (DE)
  • University of Pavol Jozef Šafárik (SK)
ORCID
Venue
Journal of Parkinson’s Disease
Publisher
SAGE Publications
Published
2023-10-09
Volume
13
Issue
7
Pages
1079-1106
ISSN
  • 1877-7171 (ISSN-L)
  • 1877-718X
DOI
10.3233/jpd-230206
PMC
PMC10657696
OpenAlex
W4388070771
Cited by
40
References
33
Citations by year
2026: 7 · 2025: 14 · 2024: 17 · 2023: 2
FWCI
1.63
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Parkinson s Disease (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • Multimedialen Archiv und Publikationsserver der Christian-Albrechts-Universität zu Kiel (Christian-Albrechts-Universität zu Kiel) (submittedVersion, cc-by-nc)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Agentúra na Podporu Výskumu a Vývoja (APVV-22-0279, APVV-22-)
  • Vedecká Grantová Agentúra MŠVVaŠ SR a SAV (VEGA 1/0712/22)
Topics
  • Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
  • Life Sciences › Agricultural and Biological Sciences › Plant Science › Pesticide Exposure and Toxicity
Keywords
Parkinson's disease, pesticides, gut microbiota, microbiome-gut-brain axis, neurotoxicity, dysbiosis, microbial metabolites, pesticide metabolism, insulin resistance, inflammation, gene-environment interaction, environmental risk factors, dopaminergic neuron damage
MeSH terms
Gastrointestinal Microbiome, Brain-Gut Axis, Humans, Parkinson Disease, Pesticides, Dysbiosis

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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