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Agrochemicals interact synergistically to increase bee mortality

Abstract

Global concern over widely documented declines in pollinators1,2,3 has led to the identification of anthropogenic stressors that, individually, are detrimental to bee populations4,5,6,7. Synergistic interactions between these stressors could substantially amplify the environmental effect of these stressors and could therefore have important implications for policy decisions that aim to improve the health of pollinators3,8,9. Here, to quantitatively assess the scale of this threat, we conducted a meta-analysis of 356 interaction effect sizes from 90 studies in which bees were exposed to combinations of agrochemicals, nutritional stressors and/or parasites. We found an overall synergistic effect between multiple stressors on bee mortality. Subgroup analysis of bee mortality revealed strong evidence for synergy when bees were exposed to multiple agrochemicals at field-realistic levels, but interactions were not greater than additive expectations when bees were exposed to parasites and/or nutritional stressors. All interactive effects on proxies of fitness, behaviour, parasite load and immune responses were either additive or antagonistic; therefore, the potential mechanisms that drive the observed synergistic interactions for bee mortality remain unclear. Environmental risk assessment schemes that assume additive effects of the risk of agrochemical exposure may underestimate the interactive effect of anthropogenic stressors on bee mortality and will fail to protect the pollinators that provide a key ecosystem service that underpins sustainable agriculture.

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Fig. 1: The interaction effects of parasites, agrochemicals and nutritional stressors on bee mortality.
Fig. 2: The interaction effects of parasites, agrochemicals and nutritional stressors on non-mortality response measures.
Fig. 3: Reversal interactions.

Data availability

All data used in this analysis are available at OSF (https://osf.io/8xnua/).

Code availability

All code used in this analysis is available at OSF (https://osf.io/8xnua/).

References

  1. Holden, C. Report warns of looming pollination crisis in North America. Science 314, 397 (2006).

    CAS  PubMed  Article  Google Scholar 

  2. Aizen, M. A. & Harder, L. D. The global stock of domesticated honey bees is growing slower than agricultural demand for pollination. Curr. Biol. 19, 915–918 (2009).

    CAS  PubMed  Article  Google Scholar 

  3. Goulson, D., Nicholls, E., Botías, C. & Rotheray, E. L. Bee declines driven by combined stress from parasites, pesticides, and lack of flowers. Science 347, 1255957 (2015).

    Article  CAS  PubMed  Google Scholar 

  4. Woodcock, B. A. et al. Impacts of neonicotinoid use on long-term population changes in wild bees in England. Nat. Commun. 7, 12459 (2016).

    CAS  PubMed  PubMed Central  Article  ADS  Google Scholar 

  5. Siviter, H., Brown, M. J. F. & Leadbeater, E. Sulfoxaflor exposure reduces bumblebee reproductive success. Nature 561, 109–112 (2018).

    CAS  PubMed  Article  ADS  Google Scholar 

  6. Cameron, S. A. et al. Patterns of widespread decline in North American bumble bees. Proc. Natl Acad. Sci. USA 108, 662–667 (2011).

    CAS  PubMed  PubMed Central  Article  ADS  Google Scholar 

  7. Powney, G. D. et al. Widespread losses of pollinating insects in Britain. Nat. Commun. 10, 1018 (2019).

    PubMed  PubMed Central  Article  ADS  CAS  Google Scholar 

  8. Vanbergen, A. J. & The Insect Pollinators Initiative. Threats to an ecosystem service: pressures on pollinators. Front. Ecol. Environ. 11, 251–259 (2013).

    Article  Google Scholar 

  9. EFSA. Bee health. https://www.efsa.europa.eu/en/topics/topic/bee-health (2019).

  10. Foley, J. A. et al. Global consequences of land use. Science 309, 570–574 (2005).

    CAS  PubMed  Article  ADS  Google Scholar 

  11. Tilman, D., Cassman, K. G., Matson, P. A., Naylor, R. & Polasky, S. Agricultural sustainability and intensive production practices. Nature 418, 671–677 (2002).

    CAS  PubMed  Article  ADS  Google Scholar 

  12. Potts, S. G. et al. Safeguarding pollinators and their values to human well-being. Nature 540, 220–229 (2016).

    CAS  PubMed  Article  ADS  Google Scholar 

  13. Pettis, J. S. et al. Crop pollination exposes honey bees to pesticides which alters their susceptibility to the gut pathogen Nosema ceranae. PLoS ONE 8, e70182 (2013).

    CAS  PubMed  PubMed Central  Article  ADS  Google Scholar 

  14. Siviter, H., Folly, A. J., Brown, M. J. F. & Leadbeater, E. Individual and combined impacts of sulfoxaflor and Nosema bombi on bumblebee (Bombus terrestris) larval growth. Proc. R. Soc. B 287, 20200935 (2020).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  15. Retschnig, G. et al. Effects, but no interactions, of ubiquitous pesticide and parasite stressors on honey bee (Apis mellifera) lifespan and behaviour in a colony environment. Environ. Microbiol. 17, 4322–4331 (2015).

    CAS  PubMed  Article  Google Scholar 

  16. Doublet, V., Labarussias, M., de Miranda, J. R., Moritz, R. F. A. & Paxton, R. J. Bees under stress: sublethal doses of a neonicotinoid pesticide and pathogens interact to elevate honey bee mortality across the life cycle. Environ. Microbiol. 17, 969–983 (2015).

    CAS  PubMed  Article  Google Scholar 

  17. Folt, C. L., Chen, C. Y., Moore, M. V. & Burnaford, J. Synergism and antagonism among multiple stressors. Limnol. Oceanogr. 44, 864–877 (1999).

    Article  ADS  Google Scholar 

  18. Di Prisco, G. et al. Neonicotinoid clothianidin adversely affects insect immunity and promotes replication of a viral pathogen in honey bees. Proc. Natl Acad. Sci. USA 110, 18466–18471 (2013).

    PubMed  PubMed Central  Article  ADS  CAS  Google Scholar 

  19. Collison, E., Hird, H., Cresswell, J. & Tyler, C. Interactive effects of pesticide exposure and pathogen infection on bee health – a critical analysis. Biol. Rev. Camb. Philos. Soc. 91, 1006–1019 (2016).

    PubMed  Article  Google Scholar 

  20. Tsvetkov, N. et al. Chronic exposure to neonicotinoids reduces honey bee health near corn crops. Science 356, 1395–1397 (2017).

    CAS  PubMed  Article  ADS  Google Scholar 

  21. Carnesecchi, E. et al. Investigating combined toxicity of binary mixtures in bees: meta-analysis of laboratory tests, modelling, mechanistic basis and implications for risk assessment. Environ. Int. 133 (Pt B), 105256 (2019).

    CAS  PubMed  Article  Google Scholar 

  22. Jackson, M. C., Loewen, C. J. G., Vinebrooke, R. D. & Chimimba, C. T. Net effects of multiple stressors in freshwater ecosystems: a meta-analysis. Glob. Change Biol. 22, 180–189 (2016).

    Article  ADS  Google Scholar 

  23. Piggott, J. J., Townsend, C. R. & Matthaei, C. D. Reconceptualizing synergism and antagonism among multiple stressors. Ecol. Evol. 5, 1538–1547 (2015).

    PubMed  PubMed Central  Article  Google Scholar 

  24. Ascher, J. S. & Pickering, J. Discover life: bee species guide and world checklist (Hymenoptera: Apoidea: Anthophila). https://www.discoverlife.org/mp/20q?guide=Apoidea_species&flags=HAS (2012).

  25. Gill, R. J., Ramos-Rodriguez, O. & Raine, N. E. Combined pesticide exposure severely affects individual- and colony-level traits in bees. Nature 491, 105–108 (2012).

    CAS  PubMed  PubMed Central  Article  ADS  Google Scholar 

  26. Schmid-Hempel, P. Evolutionary Parasitology (Oxford Univ. Press, 2011).

  27. Sánchez-Bayo, F. et al. Are bee diseases linked to pesticides? — A brief review. Environ. Int. 89–90, 7–11 (2016).

    PubMed  Article  CAS  Google Scholar 

  28. Brandt, A., Gorenflo, A., Siede, R., Meixner, M. & Büchler, R. The neonicotinoids thiacloprid, imidacloprid, and clothianidin affect the immunocompetence of honey bees (Apis mellifera L.). J. Insect Physiol. 86, 40–47 (2016).

    CAS  PubMed  Article  Google Scholar 

  29. Vaudo, A. D., Patch, H. M., Mortensen, D. A., Tooker, J. F. & Grozinger, C. M. Macronutrient ratios in pollen shape bumble bee (Bombus impatiens) foraging strategies and floral preferences. Proc. Natl Acad. Sci. USA 113, E4035–E4042 (2016).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  30. Fürst, M. A., McMahon, D. P., Osborne, J. L., Paxton, R. J. & Brown, M. J. F. Disease associations between honeybees and bumblebees as a threat to wild pollinators. Nature 506, 364–366 (2014).

    PubMed  PubMed Central  Article  ADS  CAS  Google Scholar 

  31. Cedergreen, N. Quantifying synergy: a systematic review of mixture toxicity studies within environmental toxicology. PLoS ONE 9, e96580 (2014).

    PubMed  PubMed Central  Article  ADS  CAS  Google Scholar 

  32. Carvell, C. et al. Declines in forage availability for bumblebees at a national scale. Biol. Conserv. 132, 481–489 (2006).

    Article  Google Scholar 

  33. Baude, M. et al. Historical nectar assessment reveals the fall and rise of floral resources in Britain. Nature 530, 85–88 (2016).

    CAS  PubMed  PubMed Central  Article  ADS  Google Scholar 

  34. Ovaskainen, O. et al. Community-level phenological response to climate change. Proc. Natl Acad. Sci. USA 110, 13434–13439 (2013).

    CAS  PubMed  PubMed Central  Article  ADS  Google Scholar 

  35. Carvell, C. et al. Bumblebee family lineage survival is enhanced in high-quality landscapes. Nature 543, 547–549 (2017).

    CAS  PubMed  Article  ADS  Google Scholar 

  36. Siviter, H. & Muth, F. Do novel insecticides pose a threat to beneficial insects? Proc. R. Soc. B 287, 20201265 (2020).

    PubMed  PubMed Central  Article  Google Scholar 

  37. Topping, C. J., Aldrich, A. & Berny, P. Overhaul environmental risk assessment for pesticides. Science 367, 360–363 (2020).

    CAS  PubMed  Article  ADS  Google Scholar 

  38. Sgolastra, F. et al. Bees and pesticide regulation: lessons from the neonicotinoid experience. Biol. Conserv. 241, 108356 (2020).

    Article  Google Scholar 

  39. Mullin, C. A. Effects of ‘inactive’ ingredients on bees. Curr. Opin. Insect Sci. 10, 194–200 (2015).

    PubMed  Article  Google Scholar 

  40. Colin, T., Monchanin, C., Lihoreau, M. & Barron, A. B. Pesticide dosing must be guided by ecological principles. Nat. Ecol. Evol. 4, 1575–1577 (2020).

    PubMed  Article  Google Scholar 

  41. Milner, A. M. & Boyd, I. L. Toward pesticidovigilance. Science 357, 1232–1234 (2017).

    CAS  PubMed  Article  ADS  Google Scholar 

  42. Franklin, E. L. & Raine, N. E. Moving beyond honeybee-centric pesticide risk assessments to protect all pollinators. Nat. Ecol. Evol. 3, 1373–1375 (2019

    PubMed  Article  Google Scholar 

  43. Brühl, C. A. & Zaller, J. G. Biodiversity decline as a consequence of an inappropriate environmental risk assessment of pesticides. Front. Environ. Sci. 7, 177 (2019).

    Article  Google Scholar 

  44. OECD. Test No. 245: Honey Bee (Apis Mellifera L.), Chronic Oral Toxicity Test (10-Day Feeding) (OECD, 2017).

  45. Viechtbauer, W. Conducting meta-analyses in R with the metafor package. J. Stat. Softw. 36, 1–48 (2010).

    Article  Google Scholar 

  46. Duval, S. & Tweedie, R. Trim and fill: a simple funnel-plot-based method of testing and adjusting for publication bias in meta-analysis. Biometrics 56, 455–463 (2000).

    CAS  PubMed  MATH  Article  Google Scholar 

  47. Woodcock, B. A. et al. Meta-analysis reveals that pollinator functional diversity and abundance enhance crop pollination and yield. Nat. Commun. 10, 1481 (2019).

    CAS  PubMed  PubMed Central  Article  ADS  Google Scholar 

  48. Siviter, H., Koricheva, J., Brown, M. J. F. & Leadbeater, E. Quantifying the impact of pesticides on learning and memory in bees. J. Appl. Ecol. 55, 2812–2821 (2018).

    PubMed  PubMed Central  Article  Google Scholar 

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Acknowledgements

We thank all authors who made data available to us upon request (C. Alaux, K. Antunez, B. Baer, B. Blochtein, C. Botias, B. Dainat, M. Diogon, A. G. Dolezal, V. Doublet, K. Fent, D. C. de Graaf, G. de Grandi-Hoffman, P. Graystock, E. Guzman-Novoa, R. M. Johnson, E. G. Klinger, I. M. de Mattos, N. A. Moran, M. Natsopoulou, F. Nazzi, P. Neumann, R. Odemer, R. Raimets, G. Retschnig, R. M. Roe, E. Ryabov, B. M. Sadd, C. Sandrock, F. Sgolastra, R. Siede, H. V. V. Tome, I. Toplak, S. Tosi, M. Tritschler, V. Zanni and Y. C. Zhu); and J. Bagi and A. J. Folly for helping with the initial screening of titles and abstracts. H.S. was supported by a Royal Holloway University of London Reid PhD Scholarship and by contributions from the High Wycombe Beekeeper’s Association. This project has received funding from the European Horizon 2020 research and innovation programme under grant agreement no. 773921 and ERC Starting Grant BeeDanceGap 638873, and from the Biotechnology and Biological Sciences Research Council, grant/award number BB/N000668/1.

Author information

Authors and Affiliations

Authors

Contributions

H.S., E.J.B., C.D.M., T.R.O. and M.J.F.B. conceived the idea for the study in a discussion group. H.S. and E.B. oversaw and managed the data collection. H.S., E.B., C.D.M. and T.R.O. carried out the literature search and collected the data. H.S. and E.L. conducted the statistical analysis and H.S. wrote the first version of the manuscript. H.S., E.J.B., J.K., E.L. and M.J.F.B. contributed to the writing of subsequent drafts.

Corresponding author

Correspondence to Harry Siviter.

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The authors declare no competing interests.

Additional information

Peer review information Nature thanks Antica Culina, Adam Vanbergen and the other, anonymous, reviewer(s) for their contribution to the peer review of this work. Peer reviewer reports are available.

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Extended data figures and tables

Extended Data Fig. 1 Distribution of Hedges’ d values for the individual effect sizes included for the interaction effects of parasites, agrochemicals and nutritional stressors for bee response variables.

ae, Distributions are shown for mortality (a), behaviour (b), fitness (c), parasite load (d) and immune responses (e). Data are shown as Hedges’ d values ± 95% CI. Effect sizes are sorted for each response variable from most negative to most positive. Each mean ± 95% CI represents a different data point, hence there are more effect sizes than number of studies. Interactions are synergistic when the effect size is positive and the 95% CI does not include zero, antagonistic when the effect size is negative and the 95% CI does not include zero and additive when the 95% CI includes zero. Note that each panel is presented on a different scale.

Extended Data Fig. 2 Hedges’ d values for interactions between specific stressors on bee mortality.

a, Interactions between combinations of parasite stressors. b, Interactions between combinations of parasite and nutritional stressors. Data are shown as Hedges’ d values ± 95% CI. The interactions are synergistic when the effect size is positive and the 95% CI does not include zero, antagonistic when the effect size is negative and the 95% CI does not include zero and additive when the 95% CI includes zero. Numbers next to the 95% CIs indicate the number of effect sizes in each category. Asterisks indicate that the 95% CI does not include zero.

Extended Data Fig. 3 Hedges’ d values for different bee genera.

ae, Data are shown as Hedges’ d values ± 95% CI for mortality (a), behaviour (b), fitness proxies (c), parasite load (d) and immune responses (e). The genus is indicated by the colour and shape of the symbol. Interactions are synergistic when the effect size is positive and the 95% CI does not include zero, antagonistic when the effect size is negative and the 95% CI does not include zero, and additive when the 95% CI includes zero. Numbers next to the 95% CIs indicate the number of effect sizes in each category. Asterisks indicate that the 95% CI does not include zero. Note that each panel is presented on a different scale.

Extended Data Fig. 4 The interaction effects of different agrochemical classes on bee mortality response measures.

Hedges’ d values  ± 95% CI are shown. Asterisks indicate that the 95% CI does not include zero. Numbers next to the 95% CIs indicate the number of effect sizes in each category. Note that effect sizes for azole fungicide × pyrethroid are included in both groups.

Extended Data Fig. 5 Modified PRISMA flowchart.

A flowchart depicting the number of studies included or excluded at each stage of the literature search.

Extended Data Fig. 6 Funnel plots of the full models of the interactions between specific stressors.

ae, Plots represent the models for mortality (a), behaviour (b), fitness proxies (c), parasite load (d) and immune responses (e).

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Siviter, H., Bailes, E.J., Martin, C.D. et al. Agrochemicals interact synergistically to increase bee mortality. Nature 596, 389–392 (2021). https://doi.org/10.1038/s41586-021-03787-7

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