农药残留对肠道微生物群系和人类健康的影响-110页-WN7.pdf

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1、THE IMPACT OF PESTICIDE RESIDUES ON THE GUT MICROBIOME AND HUMAN HEALTHA FOOD SAFETY PERSPECTIVEFOOD SAFETY AND QUALITY SERIES 19ISSN 24151173FAOFOOD AND AGRICULTURE ORGANIZATION OF THE UNITED NATIONSROME,2023THE IMPACT OF PESTICIDE RESIDUES ON THE GUT MICROBIOME AND HUMAN HEALTHA FOOD SAFETY PERSPE

2、CTIVERequired citation:FAO.2023.The impact of pesticide residues on the gut microbiome and human health A food safety perspective.Food Safety and Quality Series,No.19.Rome.https:/doi.org/10.4060/cc5306enThe designations employed and the presentation of material in this information product do not imp

3、ly the expression of any opinion whatsoever on the part of the Food and Agriculture Organization of the United Nations(FAO)concerning the legal or development status of any country,territory,city or area or of its authorities,or concerning the delimitation of its frontiers or boundaries.The mention

4、of specific companies or products of manufacturers,whether or not these have been patented,does not imply that these have been endorsed or recommended by FAO in preference to others of a similar nature that are not mentioned.ISSN 2415-1173 PrintISSN 2664-5246 OnlineISBN 978-92-5-137810-6 978-92-4-00

5、0629-4 electronic version(WHO)FAO,2023Some rights reserved.This work is made available under the Creative Commons Attribution-Non Commercial-ShareAlike 3.0 IGO licence(CC BY-NC-SA 3.0 IGO;https:/creativecommons.org/licenses/by-nc-sa/3.0/igo/legalcode).Under the terms of this licence,this work may be

6、 copied,redistributed and adapted for non-commercial purposes,provided that the work is appropriately cited.In any use of this work,there should be no suggestion that FAO endorses any specific organization,products or services.The use of the FAO logo is not permitted.If the work is adapted,then it m

7、ust be licensed under the same or equivalent Creative Commons licence.If a translation of this work is created,it must include the following disclaimer along with the required citation:“This translation was not created by the Food and Agriculture Organization of the United Nations(FAO).FAO is not re

8、sponsible for the content or accuracy of this translation.The original English edition shall be the authoritative edition”.Disputes arising under the licence that cannot be settled amicably will be resolved by mediation and arbitration as described in Article 8 of the licence except as otherwise pro

9、vided herein.The applicable mediation rules will be the mediation rules of the World Intellectual Property Organization http:/www.wipo.int/amc/en/mediation/rules and any arbitration will be conducted in accordance with the Arbitration Rules of the United Nations Commission on International Trade Law

10、(UNCITRAL).Thirdparty materials.Users wishing to reuse material from this work that is attributed to a third party,such as tables,figures or images,are responsible for determining whether permission is needed for that reuse and for obtaining permission from the copyright holder.The risk of claims re

11、sulting from infringement of any third-party-owned component in the work rests solely with the user.Sales,rights and licensing.FAO information products are available on the FAO website(www.fao.org/publications)and can be purchased through publications-salesfao.org.Requests for commercial use should

12、be submitted via:www.fao.org/contact-us/licence-request.Queries regarding rights and licensing should be submitted to:copyrightfao.org.Cover photographs from left to right:FAO/Michael Tewelde;FAO/Alessandra Benedetti;Bibbidistudio/SDesign and layout:studio Pietro BartoleschiiiiCONTENTSAcknowledgemen

13、ts.viAcronyms and abbreviations.viiExecutive summary.ixCHAPTER 1INTRODUCTION.1CHAPTER 2METHODOLOGY.7Scientific literature research:search criteria and strategy.7Screening of articles and selection criteria.8Pesticide dose normalization related to the acceptable daily intake.10CHAPTER 3FINDINGS.11Ind

14、ividual pesticides.122,4-dichlorophenoxyacetic acid(2,4-D).12Aldicarb.13Carbendazim.13Chlorpyrifos.14Deltamethrin.18Diazinon.19Endosulfan.20Epoxiconazole.20Glyphosate.21Imazalil.24Malathion.25Monocrotophos.26Penconazole.26Permethrin.27Propamocarb.28By-products.29Pesticide mixture and multi-residue e

15、xposure.30CHAPTER 4DISCUSSION.33Doses and exposure.35Models.37ivStudy of the microbiome and microbiome host relationship-methods.40Sampling.40Analytical considerations.42Pesticide mixture,pesticide formulations and co-exposure with other xenobiotics.44CHAPTER 5CHALLENGES.47Relevance of alterations t

16、o the microbiome and host caused by pesticide exposure.47Causality.48Gut microbiome in pesticide risk assessment.48CHAPTER 6CONCLUSIONS.51Recommendations.51BIBLIOGRAPHY.53ANNEX IMETHODOLOGY NOTES.67ANNEX IIFINDINGS.78ANNEX IIIPESTICIDE CLASSIFICATION.94FIGURES1.Gastrointestinal environment and micro

17、biota niches.22.Examples of taxonomical composition of the gut microbiota.33.Risk analysis process for the evaluation/re-evaluation of a pesticide.54.Graphic representation of the article selection process for literature review.115.Experimental pesticide doses used in the different studies relative

18、to their corresponding ADI.36vTABLE1.Manuscript coding.9AI.1 Initial search query terms and results from PubMed,Web of Science and Scopus.67AI.2 Search query terms and results for pesticide main use from PubMed,Web of Science and Scopus.68AI.3 Search query terms and results for specific pesticides f

19、rom PubMed and Web of Science.71AI.4 Search query terms and results for pesticide mixtures from PubMed and Web of Science.74AI.5 Search query terms and results for pesticide chemical types from PubMed and Web of Science.75AII.1 Summary of experimental studies reporting the impact of 2,4-D on the gut

20、 microbiome and its effects on the hosts health.78AII.2 Summary of experimental studies reporting the impact of aldicarb on the gut microbiome and its effects on the hosts health.78AII.3 Summary of experimental studies reporting the impact of carbendazim on the gut microbiome and its effects on the

21、hosts health.79AII.4 Summary of experimental studies reporting the impact of chlorpyrifos on the gut microbiome and its effects on the hosts health.80AII.5 Summary of experimental studies reporting the impact of deltamethrin on the gut microbiome and its effects on the hosts health.84AII.6 Summary o

22、f experimental studies reporting the impact of diazinon on the gut microbiome and its effects on the hosts health.85AII.7 Summary of experimental studies reporting the impact of endosulfan on the gut microbiome and its effects on the hosts health.85AII.8 Summary of experimental studies reporting the

23、 impact of epoxiconazole on the gut microbiome and its effects on the hosts health.86AII.9 Summary of experimental studies reporting the impact of glyphosate on the gut microbiome and its effects on the hosts health.86AII.10 Summary of experimental studies reporting the impact of imazalil on the gut

24、 microbiome and its effects on the hosts health.88AII.11 Summary of experimental studies reporting the impact of malathion on the gut microbiome and its effects on the hosts health.89AII.12 Summary of experimental studies reporting the impact of monocrotophos on the gut microbiome and its effects on

25、 the hosts health.89AII.13 Summary of experimental studies reporting the impact of penconazole on the gut microbiome and its effects on the hosts health.89AII.14 Summary of experimental studies reporting the impact of permethrin on the gut microbiome and its effects on the hosts health.90AII.15 Summ

26、ary of experimental studies reporting the impact of propamocarb on the gut microbiome and its effects on the hosts health.91AII.16 Summary of experimental studies reporting the impact of diethyl phosphate(non-specifc organophosphorus pestidide)on the gut microbiome and its effects on the hosts healt

27、h.92AII.17 Summary of experimental studies reporting the impact of pesticide metabolites or byproducts,p,p-dichlorodiphenyldichloroethylene (p,p-DDE)-hexachlorocyclohexane(-HCH)on the gut microbiome and its effects on the hosts health.92AII.18 Summary of experimental studies reporting the impact of

28、pesticide mixtures on the gut microbiome and its effects on the hosts health.93viACKNOWLEDGEMENTSThe research and drafting of the publication were carried out by Carmen Diaz-Amigo(Food Systems and Food Safety Division ESF,FAO)and Sarah Najera Espinosa(ESF)under the technical leadership and guidance

29、of Catherine Bessy,Senior Food Safety Officer(ESF).The support and guidance of Markus Lipp,Senior Food Safety Officer(ESF),and the technical inputs and insights provided by Vittorio Fattori,Food Safety Officer(ESF),during the entire process of the publications development are gratefully recognized.F

30、AO is grateful to the expert Mark Feeley(Consultant,Canada)for his insightful comments and recommendations to improve the draft.Finally,special thanks go out to Karel Callens Senior Advisor to Chief Economist,Governance and Policy Support Unit(DDCG,FAO)and Fanette Fontaine,Science Policy Advisor(DDC

31、G),for their pioneer initiative at FAO bringing attention to and starting a dialogue on the impact of microbiomes in food systems.viiACRONYMS AND ABBREVIATIONSADCaldicarbADIacceptable daily intakeARfDacute reference doseCARconstitutive androstane receptorCASchemical abstracts serviceCBZcarbendazimcR

32、fDChronic reference doseCPFchlorpyrifosDDTdichlorodiphenyltrichloroethaneDLMdeltamethrinDWELdrinking water equivalent levelDZNdiazinonENSendosulfanEPXepoxiconazoleERWelectrochemically reduced waterFAOFood and Agriculture Organization of the United NationsFDAUnited States Food and Drug Administration

33、GLYglyphosateGWIGulf War illnessHCHhexachlorocyclohexaneIARCInternational Agency for Research on CancerICRInstitute of Cancer ResearchIMZimazalilJECFAJoint FAO/WHO Expert Committee on Food AdditivesJMPRJoint Meeting on Pesticide ResiduesMAITmucosal-associated invariant T-cellsMCPmonocrotophosMLTmala

34、thionMRLmaximum residue limitsNOAELno observed adversed effect levelPCRpolymerase chain reactionPERMpermethrinPICprior informed consentPMBpropamocarbPNDpostnatal dayPNZpenconazolePOPpersistent organic pollutantsSCFAshort-chain fatty acidsTDItolerable daily intakeTMDItheoretical maximum daily intakeU

35、SDAUnited States Department of AgricultureWHOWorld Health OrganizationWTwild typeviii Alex Webb/Magnum Photos for FAO IAEA/Louise PottertonixEXECUTIVE SUMMARYThe gut microbiome is the microbial community composed of bacteria,viruses,fungi and archaea co-habiting in the gastrointestinal tract of anim

36、als and interacting with the host in several physiological functions,including digestion and the immune response.The gut microbiome is highly dynamic and sensitive to numerous physico-chemical factors,including pH,oxygen pressure,and diet composition.Such factors influence the diversity,composition

37、and function of the microbiome,which can impact the health status of the microbiota and the interactions with the host.Although there are no consensus definitions for the related terms“healthy microbiota”and“gut dysbiosis”,they are commonly used when explaining the potential role of the gut microbio

38、me in health and disease,respectively.Since dietary composition strongly influences the microbiome,there is a concern about the effects of chronic exposure to pesticide residues on the microbial community and consequently the impact on human health and non-communicable diseases.This systematic revie

39、w collected existing research on this topic between September 2019 and May 2020,analysed the evidence linking pesticide residuesgut microbiomehuman health and evaluated the potential use of microbiome data reported in these studies for the risk assessment of pesticide residues.Considering the high n

40、umber of existing pesticides,only a few have been evaluated in the gut microbiome,with glyphosate and chlorpyrifos receiving most attention.The majority of studies were conducted in vivo using rodent models(mice and rats)using different designs and analytical methodologies.Some in vitro models are a

41、lso reported here.Experimental doses chosen for chronic studies were usually several times higher than the established ADIs,often using as reference health-based guidance values(e.g.NOAEL),MRLs,and environmental or occupational exposures.Such high doses tend to be of limited relevance as they are no

42、t representative of chronic dietary exposures to pesticide residues.Most of the microbiome analysis focused on the evaluation of diversity and structure by sequencing the 16S rRNA gene(typically the V3-V4 hypervariable regions),resulting in more or less pronounced changes in composition after the tr

43、eatment with different pesticides.The few studies evaluating multiple doses reported dose-effect responses.The functional microbiome was only addressed in a limited number of studies,focusing primarily on the production of short-chain fatty acids,mainly acetic,propionic and butyric acids.Regarding t

44、he host,most studies focused on the evaluation of metabolism(carbendazim,chlorpyrifos,imazalil,monocrotophos,penconazole,propamocarb,p,p-DDE),immune response(carbendazim,deltamethrin,glyphosate,diethyl phosphate),intestinal homeostasis(chlorpyrifos,glyphosate,imazalil,permethrin),or other dysfunctio

45、ns(liver:epoxiconazole,xglyphosate;neurological and behavioural alterations:chlorpyrifos,glyphosate,permethrin;endocrine function:chlorpyrifos,diethyl phosphate),which in most cases and at high doses resulted in different degrees of alterations observed along with microbial disturbances.Studies focu

46、sing on maternal exposure reported that observed microbiome alterations early in life increased the predisposition or risk for developing disorders like type 2 diabetes or motor disabilities.The authors of most studies who discussed associations between observed health outcomes and microbiome altera

47、tions,often didnt provide mechanistic support or proof of cause-effect.Only two studies conducted fecal transplants with altered microbiota to reproduce host effects in germ-free or antibiotic-treated mice.FAO/Ishara KodikaraxiAlthough most studies report some degree of microbial disturbances and ho

48、st alterations after pesticide exposure,there are important limitations that should be considered with due attention when interpreting the research outcomes and using this data for risk assessment.These include the low statistical power(small sample size),the lack of standardized models and standard

49、ized analytical methodologies,and the limited consideration and control of confounding factors,which were often not reported in the publications.All these shortcomings challenge study reproducibility and the comparison of outcomes from different studies.In addition,there are other important limitati

50、ons derived from the reported research that can also delay the incorporation of microbiome data in risk assessment.These include the lack of a general discussion about the physiological relevance of observed disturbances beyond statistical significance,the lack of criteria to determine when microbio