L.I. Medved’s Research Center of Preventive Toxicology, Food and Chemical Safety, Ministry of Health, Ukraine (State Enterprise), Kyiv, Ukraine
ABSTRACT. Recent years have seen a marked increase in the interest surrounding the study of the intestinal microbiome. This is due to the recognition of the intestinal microbiome as a key factor determining human health and influencing the course of numerous diseases. Of particular interest are changes in the microbiota and its metabolites under the influence of environmental factors, in particular chemical agents such as pesticides.
Aim. To summarize current understanding of the impact of pesticides on the gut microbiome, its metabolites, and health status.
Materials and Methods. A thorough examination of contemporary publications in scientific online libraries PubMed, MedLine, Elsevier, and BioMed Central, Medscape concerning the gut microbiome was conducted. This analysis aimed to explore current concepts regarding the role of the microbiota in maintaining homeostatic mechanisms within the body. Furthermore, it sought to delineate potential pathways for the development of disorders that may emerge in the state of the gut microbiota and human health in response to long-term exposure to pesticides.
Research results. Modern research on the functional role of the intestinal microbiome and its metabolites in maintaining human health, as well as changes arising from long-term exposure to various classes of pesticides, is summarized and systematized Mechanisms of dysbiosis formation due to the action of pesticides, which cause disturbances in the quantitative and qualitative composition of the microbiota, its functional and metabolic activity, are presented. Changes in human health in response to the formation of dysbiosis in the intestinal microbial community and changes in the composition of its metabolites under the influence of pesticides are analysed.
Conclusions. The gut microbiome and its metabolites play an important role in human health by regulating metabolic homeostasis. Disruption of this balance can lead to the occurrence of many diseases. Different classes of pesticides have different effects on the gut microbiota and its metabolites, which emphasizes the need for a detailed assessment of the associated risks. A comprehensive safety assessment of pesticides should include studies of their effects on the gut microbial composition, functional activity of the microbiota and features of microbial metabolism. The mechanisms of short- and long-term effects of pesticides on the gut microbiota, its metabolites and changes in human health require further comprehensive study.
Keywords: pesticides, intestinal microbiome and its metabolites, dysbiosis.
СПИСОК ВИКОРИСТАНИХ ДЖЕРЕЛ / REFERENCES
1. Li Y, Zuo Z, Zhang B, Luo H, Song B, Zhou Z, et al. Impacts of early-life paraquat exposure on gut microbiota and body weight in adult mice. Chemosphere. 2022;291(Pt 3):133135. DOI: 10.1016/j.chemosphere.2021.133135.
2. Liu Q, Shao W, Zhang C, Xu C, Wang Q, Liu H, et al. Organochloride Pesticides Modulated Gut Microbiota and Influenced Bile Acid Metabolism in Mice. Environ Pollut. 2017;226:268–76. DOI: 10.1016/j.envpol.2017.03.068.
3. Tang W, Wang D, Wang J, Wu L, Liu Z, Li L, et al. Pyrethroid Pesticide Residues in the Global Environment: An Overview. Chemosphere. 2018;191:900–7. DOI: 10.1016/j.chemosphere.2017.10.115.
4. Бубало НМ, Балан ГМ. Метаболічні порушення, обезогенні ефекти і дисбаланс гормонів жирової тканини у хворих, які перенесли гострі та хронічні інтоксикації пестицидами. Сучас. проблеми токсикології, харч. та хім. безпеки. 2018;(2/3):51–70. DOI:10.33273/2663-4570-2018-82-83-2-3-51-70 [Bubalo NM, Balan GM. Metabolic disorders, obesogenic effects and imbalance of adipose tissue hormones in patients who have suffered acute and chronic pesticide intoxications. Modern. problems of toxicology, food. and chemical. safety. 2018;(2/3):51–70. DOI:10.33273/2663-4570-2018-82-83-2-3-51-70].
5. Sharma T, Sirpu Natesh N, Pothuraju R, Batra SK, Rachagani S. Gut Microbiota: A Non-Target Victim of Pesticide-Induced Toxicity. Gut Microbes. 2023;15:2 158778. DOI: 10.1080/19490976.2023.2187578.
6. Liu JB, Chen K, Li ZF, Wang ZY, Wang L. Glyphosateinduced gut microbiota dysbiosis facilitates male reproductive toxicity in rats. Sci Total Environ. 2022;20; 805:150368. DOI: 10.1016/j.scitotenv.2021.150368.
7. Dekaboruah E, Suryavanshi MV, Chettri D, Verma AK. Human microbiome: an academic update on human body site specific surveillance and its possible role. Arch Microbiol. 2020;202(8):2147–67. DOI: 10.1007/s00203-020-01931-x.
8. Franzosa EA, Morgan XC, Segata N, Waldron L, Reyes J, Earl AM, et al. Relating the metatranscriptome and metagenome of the human gut. Proc Natl Acad Sci U S A. 2014;3;111(22):E2329–38. DOI: 10.1073/pnas. 1319284111.
9. Янковський ДС, Широбоков ВП, Димент ГС. 2017. Мікробіом. Монографія. 2017. 640 с. ISBN 978-617-657-039-4 [Yankovsky DS, Shirobokov VP, Diment GS. 2017. Microbiome. Monograph. 2017. 640 p. ISBN 978-617-657-039-4].
10. Климнюк С. Романюк Л. Деякі особливості мікробіому людини. Інфекційні хвороби. 2024. С. 33–42. DOI: 10.11603/1681-2727.2024.4.15005 [Klymniuk S. Romaniuk L. Some features of the human microbiome. Infectious diseases. 2024. P. 33–42. DOI: 10.11603/1681-2727.2024.4.15005].
11. Широбоков ВП, Димент ГС. Зв’язок між мікробіомом кишечника та розвитком нейродегенеративних захворювань (огляд). Вісник Національної академії наук України. 2024;7:77–94. DOI: 10.15407/visn2024.07.077 [Shirobokov VP, Diment GS. The relationship between the intestinal microbiome and the development of neurodegenerative diseases (review). Bulletin of the National Academy of Sciences of Ukraine. 2024;7:77–94. DOI: 10.15407/visn2024.07.077].
12. Shyrobokov VP, Yankovsky DS, Dyment GS. Microbiome and human aging (literature review). Journal of the National Academy of Sciences of Ukraine. 2019;2:245–52. DOI: 10.37621/JNAMSU-2019-4-463-475.
13. Long-Smith C, O'Riordan KJ, Clarke G, Stanton C, Dinan TG, Cryan JF. Microbiota-Gut-Brain Axis: New Therapeutic Opportunities. Annu Rev Pharmacol Toxicol. 2020;6(60):477–502. DOI: 10.1146/annurev-pharmtox-010919-023628.
14. Tofalo R, Cocchi S, Suzzi G. Polyamines and gut microbiota. Front Nutr. 2019;6:16. DOI: 10.3389/fnut.2019.00016.
15. Das TK, Ganesh BP. Interlink between the gut microbiota and inflammation in the context of oxidative stress in Alzheimer's disease progression. Gut Microbes. 2023;15(1):2206504. DOI: 10.1080/19490976.2023.2206504.
16. Pellegrini C, Antonioli L, Colucci R, Blandizzi C, Fornai M. Interplay among gut microbiota, intestinal mucosal barrier and enteric neuro-immune system: a common path to neurodegenerative diseases? Acta Neuropathol. 2018;136(3):345–61. DOI: 10.1007/s00401-018-1856-5.
17. Alexandrov P, Zhai Y, Li W, Lukiw W. Lipopolysaccharide-stimulated, NF-kB-, miRNA-146a- and miRNA-155-mediated molecular-genetic communication between the human gastrointestinal tract microbiome and the brain. Folia Neuropathol. 2019;57(3):211–19. DOI: 10.5114/fn.2019.88449.
18. Koh A, De Vadder F, Kovatcheva-Datchary P, Bäckhed F. From dietary fiber to host physiology: short-chain fatty acids as key bacterial metabolites. Cell. 2016;165(6):1332–45. DOI:10.1016/j.cell.2016.05.041.
19. Matsumoto M. Prevention of atherosclerosis by the induction of microbial polyamine production in the intestinal lumen. Biological & Pharmaceutical Bulletin. 2020;43(2):221–9. DOI:10.1248/bpb.b19-00855.
20. Liu J, Xu Y, Jiang B. Novel Insights Into Pathogenesis and Therapeutic Strategies of Hepatic Encephalopathy, From the Gut Microbiota Perspective. Front Cell Infect Microbiol. 2021;22(11):586427. DOI: 10.3389/fcimb.2021.586427.
21. Canfora EE, Jocken JW, Blaak EE. Short-chain fatty acids in control of body weight and insulin sensitivity. Nature Reviews Endocrinology. 2015;11(10):577–91. DOI: 10.1038/nrendo.2015.128.
22. Fang B, Li JW, Zhang M, Ren FZ, Pang GF. Chronic chlorpyrifos exposure elicits diet-specific effects on metabolism and the gut microbiome in rats. Food Chem Toxicol. 2018;111:144-152. DOI: 10.1016/j.fct.2017.11.001.
23. Ho L, Ono K, Tsuji M, Mazzola P, Singh R, Pasinetti GM. Protective roles of intestinal microbiota derived short chain fatty acids in Alzheimer's disease-type beta-amyloid neuropathological mechanisms. Expert Rev Neurother. 2018;18(1):83–90. DOI: 10.1080/14737175.2018.1400909.
24. Hernandez MAG., Canfora EE, Jocken JWE, Blaak EE. The short-chain fatty acid acetate in body weight control and insulin sensitivity. Nutrients. 2019;11:1943. DOI: 10.3390/nu11081943.
25. Liu S, Gao J, Zhu M, Liu K, Zhang HL. Gut Microbiota and Dysbiosis in Alzheimer's Disease: Implications for Pathogenesis and Treatment. Mol Neurobiol. 2020;57(12):5026–43. DOI: 10.1007/s12035-020-02073-3.
26. Valles-Colomer M, Falony G, Darzi Y, et al. The neuroactive potential of the human gut microbiota in quality of life and depression. Nat Microbiol. 2019;4(4):623–32. DOI: 10.1038/s41564-018-0337-x.
27. Ghoshal UC. Gut microbiota–brain axis modulation by a healthier microbiological microenvironment: facts and fictions. Journal of Neurogastroenterology and Motility. 2018;24(1):4–6. DOI: 10.5056/jnm17150.
28. Marotz C, Cavagnero KJ, Song SJ, McDonald D, Wandro S, Humphrey G, et al. Evaluation of the Effect of Storage Methods on Fecal, Saliva, and Skin Microbiome Composition. mSystems. 2021;6(2):e01329-20. DOI: 10.1128/mSystems.01329-20.
29. Portincasa P, Bonfrate L, Vacca M, De Angelis M, Farella I, Lanza E, et al. Gut Microbiota and Short Chain Fatty Acids: Implications in Glucose Homeostasis. Int J Mol Sci. 2022;23(3):1105. DOI: 10.3390/ijms23031105.
30. Dalile B., Van Oudenhove L., Vervliet B., Verbeke K. The role of short-chain fatty acids in microbiota-gut-brain communication. Nat Rev Gastroenterol Hepatol. 2019;16(8):461–78. DOI: 10.1038/s41575-019-0157-3.
31. Silva YP, Bernardi A, Frozza RL. The Role of Short-Chain Fatty Acids From Gut Microbiota in Gut-Brain Communication. Front Endocrinol (Lausanne). 2020;31(11): 25. DOI: 10.3389/fendo.2020.00025.
32. Lee S, Portlock T, Le Chatelier E, Garcia-Guevara F, Clasen F, Onate FP, et al. Global compositional and functional states of the human gut microbiome in health and disease. Genome Res. 2024;34(6):967-978. DOI: 10.1101/gr.278637.123.
33. Rodríguez LV, Lopez-Santamarina A, del Carmen Mondragón A, Regal P, Lamas A, et al. Effects of Pesticides Carried by Foods on Human Gut Microbiota. Letters in Functional Foods. 2023;1(1). DOI: 10.2174/2666939001666230516140536.
34. Ali A, AlHussaini KI. Pesticides: Unintended Impact on the Hidden World of Gut Microbiota. Metabolites. 2024;7;14(3):155. DOI: 10.3390/metabo14030155.
35. Velmurugan G, Ramprasath T, Gilles M, Swaminathan K, Ramasamy S. Gut Microbiota, Endocrine-Disrupting Chemicals, and the Diabetes Epidemic. Trends Endocrinol Metab. 2017;28(8):612–25. DOI: 10.1016/j.tem.2017. 05.001.
36. Yuan X, Pan Z, Jin C, Ni Y, Fu Z, Jin Y. Gut microbiota: An underestimated and unintended recipient for pesticideinduced toxicity. Chemosphere. 2019;227:425–34. DOI: 10.1016/j.chemosphere.2019.04.088.
37. Réquilé M, Gonzàlez Alvarez DO, Delanaud S, Rhazi L, Bach V, et al. Use of a combination of in vitro models to investigate the impact of chlorpyrifos and inulin on the intestinal microbiota and the permeability of the intestinal mucosa. Environ Sci Pollut Res Int. 2018;25(23):22529–40. DOI: 10.1007/s11356-018-2332-4.
38. Giambò F, Teodoro M, Costa C, Fenga C. Toxicology and Microbiota: How Do Pesticides Influence Gut Microbiota? A Review. Int J Environ Res Public Health. 2021;18(11):5510. DOI: 10.3390/ijerph18115510.
39. Zhao Y, Zhang Y, Wang G, Han R, Xie X. Effects of chlorpyrifos on the gut microbiome and urine metabolome in mouse (Mus musculus). Chemosphere. 2016;153:287–93. DOI: 10.1016/j.chemosphere.2016.03.055.
40. Wang X, Shen M, Zhou J, Jin Y. Chlorpyrifos disturbs hepatic metabolism associated with oxidative stress and gut microbiota dysbiosis in adult zebrafish. Comp Biochem Physiol C Toxicol Pharmacol. 2019;216:19–28. DOI: 10.1016/j.cbpc.2018.11.010.
41. Aggarwal V, Deng X, Tuli A, Goh KS. Diazinon-chemistry and environmental fate: a California perspective. Rev Environ Contam Toxicol. 2013;223:107–40. DOI: 10.1007/978-1-4614-5577-6_5.
42. Gao B, Bian X, Chi L, Tu P, Ru H, Lu K. Editor's Highlight: OrganophosphateDiazinon Altered Quorum Sensing, Cell Motility, Stress Response, and Carbohydrate Metabolism of Gut Microbiome. Toxicol Sci. 2017;157(2):354–64. DOI: 10.1093/toxsci/kfx053.
43. Kandel Gambarte PC, Wolansky MJ. The gut microbiota as a biomarker for realistic exposures to pesticides: A critical consideration. Neurotoxicol Teratol. 2022;91:107074. DOI: 10.1016/j.ntt.2022.107074.
44. 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 Jan 24;18(1):8. DOI: 10.1186/s13059-016-1134-6.
45. Slotkin TA. Does early-life exposure to organophosphate insecticides lead to prediabetes and obesity? Reprod Toxicol. 2011;31(3):297–301. DOI: 10.1016/j.reprotox.2010.07.012.
46. Tokuhara D. Role of the Gut Microbiota in Regulating Non-alcoholic Fatty Liver Disease in Children and Adolescents. Front Nutr. 2021;25;8:700058. DOI: 10.3389/fnut.2021.700058.
47. Abou Diwan M, Lahimer M, Bach V, Gosselet F, KhorsiCauet H, Candela P. Impact of Pesticide Residues on the Gut-Microbiota-Blood-Brain Barrier Axis: A Narrative Review. Int J Mol Sci. 2023;24(7):6147. DOI: 10.3390/ijms24076147.
48. Karami-Mohajeri S, Abdollahi M. Toxic influence of organophosphate, carbamate, and organochlorine pesticides on cellular metabolism of lipids, proteins, and carbohydrates: a systematic review. Hum Exp Toxicol. 2011;30(9):1119–40. DOI: 10.1177/0960327110388959.
49. Leung MCK., Meyer JN. Mitochondria as a target of organophosphate and carbamate pesticides: Revisiting common mechanisms of action with new approach methodologies. Reprod Toxicol. 2019;89:83–92. DOI: 10.1016/j.reprotox.2019.07.007.
50. Zhang K, Paul K, Jacobs JP, et al. Ambient long-term exposure to organophosphorus pesticides and the human gut microbiome: an observational study. Environ Health. 2024;23(1):41. DOI: 10.1186/s12940-024-01078-y.
51. 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(1):213. DOI: 10.3390/ijerph20010213.
52. Li M, Liu T, Yang T, Zhu J, Zhou Y, Wang M, et al. Gut microbiota dysbiosis involves in host non-alcoholic fatty liver disease upon pyrethroid pesticide exposure. Environ Sci Ecotechnol. 2022;11:100185. DOI: 10.1016/ j.ese.2022.100185.
53. Wei X, Peng H, Li Y, Meng B, Wang S, Bi S, et al. Pyrethroids exposure alters the community and function of the internal microbiota in Aedes albopictus. Ecotoxicol Environ Saf. 2023;252:114579. DOI: 10.1016/j.ecoenv.2023.114579.
54. Jin Y, Zeng Z, Wu Y, Zhang S, Fu Z. Oral Exposure of Mice to Carbendazim Induces Hepatic Lipid Metabolism Disorder and Gut Microbiota Dysbiosis. Toxicol Sci. 2015;147(1):116–26. DOI: 10.1093/toxsci/kfv115.
55. Meng Z, Liu L, Yan S, Sun W, Jia M, Tian S, et al. Gut Microbiota: A Key Factor in the Host Health Effects Induced by Pesticide Exposure? J Agric Food Chem. 2020;68(39):10517–31. DOI: 10.1021/acs.jafc.0c04678.
56. Wu S, Luo T, Wang S, Zhou J, Ni Y, Fu Z, et al. Chronic exposure to fungicide propamocarb induces bile acid metabolic disorder and increases trimethylamine in C57BL/6J mice. Sci Total Environ. 2018;642:341–8. DOI: 10.1016/j.scitotenv.2018.06.084.
57. Jin C, Zeng Z, Wang C, Luo T, Wang S, Zhou J, et al. Insights into a Possible Mechanism Underlying the Connection of Carbendazim-Induced Lipid Metabolism Disorder and Gut Microbiota Dysbiosis in Mice. Toxicol Sci. 2018;166(2):382–93. DOI: 10.1093/toxsci/kfy205.
58. Gao JH, Guo LJ, Huang ZY, Rao JN, Tang CW. Roles of cellular polyamines in mucosal healing in the gastrointestinal tract. J Physiol Pharmacol. 2013;64(6):681–93. PMID: 24388882.
59. Jin C, Zeng Z, Fu Z, Jin Y. Oral imazalil exposure induces gut microbiota dysbiosis and colonic inflammation in mice. Chemosphere. 2016;160:349–58. DOI: 10.1016/j.chemosphere.2016.06.105.
60. Jin C, Luo T, Zhu Z, Pan Z, Yang J, Wang W, et al. Imazalil exposure induces gut microbiota dysbiosis and hepatic metabolism disorder in zebrafish. Comp Biochem Physiol C Toxicol Pharmacol. 2017;202:85–93. DOI: 10.1016/j.cbpc.2017.08.007.
61. 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: 10.1016/j.ntt.2018.04.002.
62. 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(2):29. DOI:10.3390/medsci6020029.
63. Agostini LP, Dettogni RS, Dos Reis RS, Stur E, Dos Santos EVW, Ventorim DP, et al. Effects of glyphosate exposure on human health: Insights from epidemiological and in vitro studies. Sci Total Environ. 2020;25;705:135808. DOI: 10.1016/j.scitotenv.2019.135808.
64. Paul KC, Ling C, Lee A, To TM, Cockburn M, Haan M, et al. Cognitive decline, mortality, and organophosphorus exposure in aging Mexican Americans. Environ Res. 2018;160:132–9. DOI: 10.1016/j.envres.2017.09.017.
65. 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: 10.3389/fnbeh.2017.00146.
66. Matsuzaki R, Gunnigle E, Geissen V, Clarke G, Nagpal J, Cryan JF. Pesticide exposure and the microbiota-gut-brain axis. ISME J. 2023;17(8):1153–66. DOI: 10.1038/s41396-023-01450-9.
67. Cryan JF, Mazmanian SK. Microbiota-brain axis: Context and causality. Science. 2022;376(6596):938–9. DOI:10.1126/science.abo4442.
68. Gao B, Chi L, Tu P, Gao N, Lu K. The Carbamate Aldicarb Altered the Gut Microbiome, Metabolome, and Lipidome of C57BL/6J Mice. Chem Res Toxicol. 2019;32(1):67–79. DOI: 10.1021/acs.chemrestox.8b00179.
69. Mesnage R, Bowyer RCE, El Balkhi S, Saint-Marcoux F, Gardere A, Ducarmon QR, et al. Impacts of dietary exposure to pesticides on faecal microbiome metabolism in adult twins. Environ Health. 2022;21(1):46. DOI: 10.1186/s12940-022-00860-0.
70. Zhu L, Qi S, Xue X, Niu X, Wu L. Nitenpyram disturbs gut microbiota and influences metabolic homeostasis and immunity in honey bee (Apis mellifera L.). Environ Pollut. 2020;258:113671. DOI: 10.1016/j.envpol.2019.113671.
71. Al Naggar Y, Singavarapu B, Paxton RJ, Wubet T. Bees under interactive stressors: the novel insecticides flupyradifurone and sulfoxaflor along with the fungicide azoxystrobin disrupt the gut microbiota of honey bees and increase opportunistic bacterial pathogens. Sci Total Environ. 2022;849:157941. DOI: 10.1016/j.scitotenv. 2022.157941.
72. Meng Z, Huang S, Sun W, Yan S, Chen X, Diao J, et al. A Typical Fungicide and Its Main Metabolite Promote Liver Damage in Mice through Impacting Gut Microbiota and Intestinal Barrier Function. J Agric Food Chem. 2021;69(45):13436–47. DOI: 10.1021/acs.jafc.1c05508.
73. Fan Y, Pedersen O. Gut microbiota in human metabolic health and disease. Nat Rev Microbiol. 2021;19(1):55–71. DOI: 10.1038/s41579-020-0433-9.
74. Liang Y, Zhan J, Liu D, Luo M, Han J, Liu X, et al. Organophosphorus Pesticide Chlorpyrifos Intake Promotes Obesity and Insulin Resistance through Impacting Gut and Gut Microbiota. Microbiome. 2019;7:19. DOI: 10.1186/s40168-019-0635-4.
75. Pietri JE, Tiffany C, Liang D. Disruption of the microbiota affects physiological and evolutionary aspects of insecticide resistance in the German cockroach, an important urban pest. PLoS One. 2018;13(12):e0207985. DOI: 10.1371/journal.pone.0207985.
76. Sandoval-Insausti H, Chiu YH, Wang YX, Hart JE, Bhupathiraju SN, Mínguez-Alarcón L, et al. Intake of fruits and vegetables according to pesticide residue status in relation to all-cause and disease-specific mortality: Results from three prospective cohort studies. Environ Int. 2022;159:107024. DOI: 10.1016/j.envint.2021.107024.
77. Chen L, Yan H, Di S, Guo C, Zhang H, et al. Mapping pesticide-induced metabolic alterations in human gut bacteria. Nat Commun. 2025;16(1):4355. DOI: 10.1038/s41467-025-59747-6.
Received December, 4, 2025
Review dates February, 26, 2026; March, 28, 2026
Publication date June, 12, 2026
