Environment International 131 (2019) 105059 Contents lists available at ScienceDirect Environment International journal homepage: www.elsevier.com/locate/envint Review article Soil biota, antimicrobial resistance and planetary health T a,b,⁎ c b,d e f,g h Yong-Guan Zhu , Yi Zhao , Dong Zhu , Michael Gillings , Josep Penuelas , Yong Sik Ok , Anthony Caponi, Steve Banwartj a State Key Lab of Urban and Regional Ecology, Research Center for Eco-environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China b Key Lab of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen 361021, China c Section for Microbial Ecology and Biotechnology, Department of Plant and Environmental Sciences, University of Copenhagen, Thorvaldsenvej 40, DK-1871 Frederiksberg C, Denmark d University of Chinese Academy of Sciences, 19A Yuquan Road, Beijing 100049, China e Department of Biological Sciences, Macquarie University, Sydney, NSW 2109, Australia f CSIC, Global Ecology Unit, CREAF-CSIC-UAB, Bellaterra, 08193 Barcelona, Catalonia, Spain g CREAF, Cerdanyola del Vallès, 08193 Barcelona, Catalonia, Spain h Korea Biochar Research Center, Division of Environmental Science and Ecological Engineering, Korea University, Seoul, Republic of Korea i Planetary Health Platform, University of Sydney, Sydney, NSW, Australia j School of Earth and Environment, University of Leeds, Leeds LS2 9JT, United Kingdom A R T I C LE I N FO A B S T R A C T Handling Editor: Adrian Covaci The concept of planetary health acknowledges the links between ecosystems, biodiversity and human health and Keywords: well-being. Soil, the critical component of the interconnected ecosystem, is the most biodiverse habitat on Earth, Planetary health and soil microbiomes play a major role in human health and well-being through ecosystem services such as Human health nutrient cycling, pollutant remediation and synthesis of bioactive compounds such as antimicrobials. Soil is also Soil microbiome a natural source of antimicrobial resistance, which is often termed intrinsic resistance. However, increasing use Antimicrobials and misuse of antimicrobials in humans and animals in recent decades has increased both the diversity and Resistome prevalence of antimicrobial resistance in soils, particularly in areas affected by human and animal wastes, such as organic manures and reclaimed wastewater, and also by air transmission. Antimicrobials and antimicrobial resistance are two sides of the sword, while antimicrobials are essential in health care; globally, antimicrobial resistance is jeopardizing the effectiveness of antimicrobial drugs, thus threatening human health. Soil is a crucial pathway through which humans are exposed to antimicrobial resistance determinants, including those harbored by human pathogens. In this review, we use the nexus of antimicrobials and antimicrobial resistance as a focus to discuss the role of soil in planetary health and illustrate the impacts of soil microbiomes on human health and well-being. This review examines the sources and dynamics of antimicrobial resistance in soils and uses the perspective of planetary health to track the movement of antimicrobial-resistance genes between en- vironmental compartments, including soil, water, food and air. 1. Introduction viewed conventionally. For example, rising atmospheric CO2 con- centrations may lead to zinc malnutrition, as they limit nutrient uptake Planetary health is a new field examining the links between human by crop plants (Nakandalage et al., 2016). health and the natural environment (Clark, 2015; Seltenrich, 2018; Al- Planetary health requires interdisciplinary studies to address com- Delaimy, 2018). Planetary health acknowledges that human health and plex and cross-cutting issues (Seltenrich, 2018). The emergence of new well-being are inextricably linked to planetary systems, and the in- systems knowledge will help to anticipate and manage the unpredict- tegrity of the natural environment needs to be protected to ensure the ability of Earth systems into the future. Studies of planetary health will long-term health of human populations (Cole and Bickersteth, 2018). help to unite disparate fields, from the arts to the sciences, in the same Planetary health specifically addresses the interconnectivity of pro- manner that Anthropocene studies provide an umbrella for inter- cesses and phenomena, some of which may not seem connected when disciplinarity (Gillings and Hagan-Lawson, 2014). Planetary health ⁎ Corresponding author at: State Key Lab of Urban and Regional Ecology, Research Center for Eco-environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China. E-mail address: ygzhu@rcees.ac.cn (Y.-G. Zhu). https://doi.org/10.1016/j.envint.2019.105059 Received 27 March 2019; Received in revised form 21 June 2019; Accepted 23 July 2019 0160-4120/ © 2019 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/BY/4.0/). Y.-G. Zhu, et al. Environment International 131 (2019) 105059 Fig. 1. The role of soil biota in supporting the planetary health system. Soil biota constitutes a complex food web, through which soil offers an array of ecosystem services to human, thus safeguarding planetary health. studies thus facilitate the engagement of all stakeholders in the stew- The chemical composition of soil can have direct impacts on human ardship of a common future. health, but the soil microbiota is also critically important in safe- Soil is a critical component of the planetary health system (Fig. 1). It guarding human health. Soil is arguably the most biodiverse habitat on plays a fundamental role in human health and well-being, primarily Earth. A gram of soil can contain a billion bacterial cells, of ten thou- because most food is derived from soil – plants represent the major sand species (Fierer, 2017). Soil microbiota play multiple roles in pathway for the delivery of essential nutrients, such as nitrogen, providing ecosystem services relevant to human health, including food phosphorus and trace elements, to humans (Beavington, 2000; Steffan production, nutrient cycling and bioremediation (Ikoyi et al., 2018). et al., 2018). The flourishing of early civilizations in the “fertile cres- Direct roles in plant nutrition, such as those that occur via mutualisms cent” demonstrates the contribution of soil to human development and the ability to mobilize key nutrients, are well known, but other (Roquero De Laburu, 2000). The functions of soil from biological, more indirect effects on human health are only just beginning to be chemical and physical perspectives consequently have direct impacts explored. For example, exposure to the soil microbiome can alleviate on human health and well-being (Fig. 1). human allergies (Prescott, 2013), which may partly account for the The provision of these soil services to humans is currently being increased prevalence of allergies and perturbations to immune re- degraded by human activity. For example, human activity can increase sponses in cities, where there is less contact with soils and other natural soil concentrations of pollutants to levels high enough to pose long-term ecosystems. health risks to humans consuming contaminated crop and animal pro- Ecosystem services provided by soil biota are also under threat from ducts (Li et al., 2014). For example, soil contaminated by arsenic due to human activity (Sharma et al., 2009; Barrios, 2007; Wardle et al., industrial activity and irrigation with contaminated groundwater has 2004). Soil is a rich source of bioactive compounds that can be explored led to elevated arsenic levels in rice (Abedin et al., 2002; Gillispie et al., as pharmaceuticals (Bahram et al., 2018). Soil, however, is also a re- 2015), which is now recognized as a major source of human exposure to servoir of antimicrobial resistance and can act as a source of resistance arsenic. Indeed, an estimated 60% of arsenic ingestion in China is from determinants that can spread to human pathogens (Forsberg et al., rice, and this presents a significantly increased risk of cancer for the 2014; Wright, 2010; Forsberg et al., 2012). Antimicrobial resistance is general population (Li et al., 2011a). recognized as one of the biggest threats to global public health and food 2 Y.-G. Zhu, et al. Environment International 131 (2019) 105059 security, which has received increasing attention over the past years ARGs are collectively known as the intrinsic resistome, and they vastly (Laxminarayan et al., 2013). There are hundreds of thousands human outnumber the resistance genes that have become clinically relevant. deaths each year worldwide attributable to antimicrobial-resistant in- The intrinsic resistome is also diverse. The molecular mechanisms fections, and scientists predicted this number will reach 10 million in that underlie the intrinsic resistome often involve inherent character- 2050 when the antimicrobial-resistant infection will become a bigger istics that are either structural (e.g., affecting the outer membrane) or killer than cancer (O'neill, 2014). The antimicrobial resistome has the functional (e.g., affecting efflux pumps) (Blair et al., 2015). Moreover, significant relevance to human health since it is immanent, highly like ARGs themselves, this mechanistic diversity arose independently of mobile, and has the capability of causing failures in the antibiotic human activity – for example, a metagenomic analysis of DNA from treatment for infectious diseases in human. There is a variety of routes 30,000-year-old permafrost identified high diversity in the intrinsic of antimicrobial resistome transmission from soil to human including resistome, with genes encoding resistance to multiple drugs (β-lactams, direct contact, food chain, and water/air environment as a transfer glycopeptides and tetracycline antibiotics) (Galán et al., 2013). ARGs stop, consequently posing a threat to public health (Ashbolt et al., 2013; with diverse resistance mechanisms have also been identified in remote Li et al., 2018a; Larsson et al., 2018; Ochoa-Hueso, 2017). For example, Antarctic soils with little human impact (Goethem et al., 2018). antimicrobial resistance in soils can be absorbed by plants and subse- quently migrate into the food chain (Chen et al., 2019). Meanwhile, soil 3.2. Humans enrich the soil resistome resistome also could spread to water bodies by naturally surface runoff and could be aerosolized into the air, facilitating further transport of The advent of antibiotics in the 20th century revolutionized medi- antimicrobial resistome with soil origins to human (Zhu et al., 2017). cine, and easy access to antibiotics has saved millions of lives and en- In this paper, we use the connection between antimicrobials and abled high-density animal production; however, it has also led to antimicrobial resistance as an example to demonstrate the complex misuse and overuse. According to the Centers for Disease Control and feedbacks that occur when humans perturb environmental processes. Prevention in the USA, up to half of antibiotics used in humans are These complex feedbacks are discussed in the context of broad eco- unnecessary or inappropriate (States, 2017). A large amount of anti- system dynamics within the framework of planetary health. Here, our biotics are used in livestock production for disease treatment, or more aims are to examine the sources and dynamics of antimicrobial re- frequently, as a growth promoter – in China 96 million kg were used in sistance in the soil ecosystem and use the perspective of planetary 2007, whereas in the USA over 384 million kg were used in 1999. health to track the movement of antimicrobial-resistance genes be- Sustained selection pressure on bacteria by antibiotic use has led to tween environmental compartments, including soil, animal, water, food increased prevalence of ARGs in a wide variety of clinical pathogens and air. Finally, we advance the recommendations for future research. and commensal bacteria. Bacteria become resistant to antibiotics by diverse mechanisms, including mutational modification of genes for 2. Soil: A source of bioactive compounds antibiotic target molecules, or acquisition of ARGs via lateral gene transfer. These mechanisms have been the subject of recent reviews Soil microorganisms produce a wide array of secondary metabolites, (Peterson and Kaur, 2018; Lambert, 2005; Qiao et al., 2018; Sultan including antibiotics. These compounds may be primarily used in et al., 2018). communication and competition with other organisms, and to adapt to New antibiotic-resistant bacteria are then shed from humans and environmental changes (Audrain et al., 2015). Microbial secondary animals into the environment and have become recognized as an im- metabolites comprise two major families: non-ribosomal peptides and portant environmental contaminant (Wright, 2010; Forsberg et al., polyketides. These two families account for most antibiotics, anti- 2012). In particular, there has been an enrichment of a specific subset fungals and other antimicrobial compounds that have been character- of clinically relevant ARGs in the environment (Peterson and Kaur, ized from culturable bacteria (Lorena et al., 2014; Guzman et al., 2012). 2018). This enrichment has reached the stage where endemic resistant During the 1940s–60s, many antibiotics were initially isolated by microorganisms in soils no longer represent the majority of resistant screening streptomycetes from soils for antimicrobial activity, including organisms in the soil microbial population. Instead, resistant micro- streptomycin, which was discovered by 1952 Nobel Prize Winner organisms increasingly acquire their resistance from human activity. Selman Waksman and his colleagues. More recently, the advent of Human activity also exposes soils to pollutants, such as antibiotics, molecular and genomic technologies has led to a resurgence of interest heavy metals or disinfectants, that are themselves selective agents in mining antibiotics from the soil microbiome, with high-throughput (Fig. 2). Subinhibitory concentrations of antibiotics raise the back- genomic tools now being used in the search for bioactive compounds ground rates of mutation, recombination and lateral gene transfer (Tong et al., 2017; Hautbergue et al., 2018). among microbial populations. These effects indicate that previously susceptible soil microbes can more readily acquire antibiotic resistance 3. Soil: A major reservoir of the environmental resistome via mutation or lateral gene transfer from co-polluting resistant bacteria (Hotopp et al., 2007; Durao et al., 2018; Knopp and Andersson, 2018). 3.1. The intrinsic resistome Lateral gene transfer can continue to propagate these genes through the soil microbiota via conjugation, transformation and transduction, Genes that can confer resistance to antibiotics are referred to as mediated by mobile genetic elements. Genes for resistance to disin- antibiotic-resistance genes (ARGs), regardless of their originally as- fectants and heavy metals are often on the same mobile elements as cribed function (Perron et al., 2013). A subset of these genes has rapidly ARGs, and thus co-selection then becomes a driving force for promoting and vastly increased in abundance, largely driven by selection imposed and fixing resistance determinants in soil microbial populations (Zhao by the application of clinical concentrations of antibiotics. As a result of et al., 2019; Pal et al., 2015; Khan et al., 2016). the increased transmission and abundance of these genes in humans, Rapid expansions in the diversity and abundance of ARGs in soil food producing animals and domestic animals, clinically relevant ARGs have been documented (Bengtsson-Palme et al., 2018; Zhu et al., 2017). are now considered to be emerging environmental contaminants While historical data are rare, there is no evidence of ARGs on plasmids (Wright, 2010; Devarajan et al., 2015). in the pre-antibiotic era (Hughes and Datta, 1983) and that resistance Like antibiotics, ARGs occur naturally (D'Costa et al., 2011). Since genes have increased in abundance in archived soils over time (Knapp penicillin was first isolated in 1928 (Chain et al., 1940), diverse anti- et al., 2010). Wastewater-treatment plants are believed to be the biotics was discovered and introduced in the 1940s. Soil harbors di- principal anthropogenic sources of resistance genes into soil (Rizzo verse microbes that produce antibiotics, and is therefore a vast natural et al., 2013). Resistance determinants from clinical settings, pharma- reservoir of the corresponding ARGs. These naturally occurring soil ceutical industries, private households and other origins enter 3 Y.-G. Zhu, et al. Environment International 131 (2019) 105059 Fig. 2. The effects of anthropogenic activity on antimicrobial resistance in the soil ecosystem. Urbanization intensifies the dispersal of resistance genes in the soil environment and beyond, therefore threatening planetary health. treatment plants, where they are often poorly removed before the re- selecting ARGs in air could be transported cross physical barriers and leased effluent carries these determinants into environmental com- settled even to soils in remote regions, exacerbating the soil selection partments. For example, over 200 resistance genes were detected in a and dissemination of ARGs. In return, soil pollutants and microbes may series of Chinese wastewater-treatment plants, with a considerable also be aerosolized into the air and further aggravate ARG spread in air. proportion of these genes persisting during treatment to then become Moreover, the soil bacteria commonly vary from one location to enriched in sewage sludge and effluents (An et al., 2018). These re- another, and they respond to the environment differently. This leads to sistance elements can contaminate urban soils and agricultural land via effects of human activities on ARGs existing difference in different re- irrigation with reclaimed water or application of sewage sludge (Qiao gions. A recent study has showed that soil types had a significant effect et al., 2018; Wang et al., 2014a; Wang et al., 2014b; Su et al., 2017). on the dispersal of ARGs after the application of sludge composts Resistance genes in urban park soils can be enriched more than 8000- (Zhang et al., 2018). In addition to direct transport from anthropogenic fold after irrigation with reclaimed water (Wang et al., 2014a). A recent sources, the wide range of antibiotic-resistant microbes in soil are also study found that the application of sewage sludge facilitated a shift in enriched by the selection process under stress from exogenous con- the microbiome of arable land and enriched resistance genes more than taminants such as antibiotic residues, toxic metals, and biocides, which 3000-fold (Chen et al., 2016). enter the soil from urban wastewater, agriculture and industry (Pal Animal manure is also widely used as a soil amendment for cost- et al., 2015). Specifically, resistant microbes have a selective advantage effective crop production (Insam et al., 2015; Zeng et al., 2017). The under such conditions and can become dominant members of the soil intensive use of in-feed antibiotics and metals as growth promotors microbial population. Their ARGs can spread to susceptible bacteria via massively enriches ARGs in the animal gut (Zhao et al., 2018) and as- lateral gene transfer, creating a cycle of positive feedback for propa- sociated environments (Zhu et al., 2013). These genes are then released gating resistance in the soil microbiota. Soil thus serves as a reservoir to soils and enriched during manure application (Zhu et al., 2013; for both intrinsic and more recently acquired resistance determinants, Zhang et al., 2017; Xie et al., 2018). Comprehensive evidence suggests at a time when soil security is becoming ever more important for human that manure use promotes the enrichment and dissemination of re- and environmental health. sistance in soils and the general environment. Air pollution is also potentially introducing ARGs to soils through wet and dry deposition (Li et al., 2018b). A global survey reported the 4. Resistance in the gut microbiomes of soil fauna ARG spread in air crossing 19 international cities and highlights the threat of urban airborne transmission of ARGs and the importance of Soil fauna are an essential component of soil ecosystems – indeed, studying PM2.5-borne ARGs (Li et al., 2018b). A recent study in- they represent 23% of known animals (Lavellea et al., 2006). Soil fauna vestigated the airborne ARGs in highly polluted air in Beijing and re- substantially contribute to planetary health by influencing litter de- ported that up to 30% of positive detection of ARGs in polluted air was composition, nutrient cycling, energy transfer, maintenance of biodi- attributed to multidrug resistant NDM-1 gene, with carrier Bacillus ha- versity and degradation of pollutants (Rusek, 1998; De Deyn et al., lotolerans disseminate more diverse ARGs (Zhang et al., 2019). These 2003). Microorganisms routinely colonize animals, where they sig- airborne resistance determinants and other pollutants that potentially nificantly affect host nutrition, development and immunity (Adair et al., 2018; Thaiss et al., 2016). Recent studies have reported that soil 4 Y.-G. Zhu, et al. Environment International 131 (2019) 105059 fauna have abundant bacterial communities in their guts and that these Both the soil microbiome and soil fauna have ancient and complex communities differ significantly from the soil communities surrounding interactions with endemic antibiotics and ARGs. These relationships the host (Maureen et al., 2016; Pass et al., 2015; Zhu et al., 2018a). This existed long before antibiotic use became widespread in human and suggests the existence of a hidden soil microbiome residing within the animal medicine. Soil organisms are thus preadapted to respond rapidly digestive tracts of soil fauna. to anthropogenic pollution with antibiotics and other selective agents. Soil fauna are constantly exposed to large numbers of microorgan- They already have the genes, the mobile elements and the biochemical isms within the soil matrix and thus are likely to have developed pathways for dealing with such compounds, and these abilities have strategies for controlling microbial growth and colonization by patho- been improved by millions of years of evolution. It is therefore not gens. One such strategy could involve harnessing the production of surprising that these organisms can respond rapidly to perturbations antimicrobial agents by gut microbiota, which would then enhance the driven by human pollution. The abundance of specific organisms, genes immunity of the host. This strategy might also provide a rich resource and phenotypes can be influenced by pollution with clinical antibiotics for the discovery of new antimicrobials (Broza et al., 2001; Dromph and or bacterial cells that carry clinically relevant ARGs, which in turn af- Vestergaard, 2002). A previous study isolated many bacteria from fects the ARG content of the soil microbiome and the microbiota re- collembolan guts that showed inhibitory effects on other microorgan- siding within soil fauna. isms – including a bacterium that could inhibit the activity of all bac- The increasing abundance of ARGs in soil has clear and direct im- terial and fungal pathogens tested (Agamennone et al., 2018). These plications for human health and clinical practice due to the link be- observations suggest that gut microbiota from soil fauna are a neglected tween soils and food production and the consequent direct route for source of new antimicrobials. novel resistance determinants to transfer from soil to food to human Soil fauna may also produce their own antimicrobial agents. For commensal and pathogenic bacteria. The dynamics, frequencies and example, multiple antimicrobial peptides have been isolated from foci of such events, however, are still being actively investigated. This earthworm tissues (Li et al., 2011b; Liu et al., 2004). Genes for anti- issue is further exacerbated by the potential co-selection of ARGs by biotic production may have been transferred from bacteria to their other chemical contaminants, such as metals and pharmaceutical hosts in some cases. Gene pathways for the synthesis of β-lactam an- compounds. tibiotics have been found in the genome of soil-dwelling collembolans, However, the potential for more general perturbations to soil eco- but are much rarer in sister taxa that live in leaf litter or on the soil systems and thus planetary processes remains unclear. Changes to the surface, and are completely absent in other closely related insect relative abundances of soil taxa, both microbial and faunal, are likely to groups. This surprising finding has been confirmed by genomic, tran- have flow-on effects to the larger-scale processes mediated by these scriptomic and phylogenetic analyses, and strongly suggests lateral organisms – however, these biogeochemical consequences are not yet gene transfer from a microbial donor in a deep-rooted collembolan known. Moreover, the intimate relationships between soil health and ancestor (Roelofs et al., 2013; Suring et al., 2016; Suring et al., 2017). soil fauna may be altered to the detriment of soil ecosystems more Human activities alter the abundance and diversity of ARGs in the generally. A “One Health” perspective is needed, taking into account soil environment (Wright, 2010; Chen et al., 2018). The resident fauna the dynamics of antibiotics and ARGs as they move from human- preferentially graze on this material when manure is applied to soil, and dominated ecosystems to more natural environments and back again thus through that manure, the soil fauna and their gut microbiota are (Food and Agriculture Organization of the United Nations et al., 2008; likely to be exposed to both ARGs and antibiotics. In a study of dietary World Health Organization, 2015). There is a pressing need to quantify exposure to antibiotics, the number and abundance of ARGs sig- the extent of selective agents being added to soil ecosystems by human nificantly increased in the collembolan gut microbiome after antibiotic activity and to examine their consequences for the endemic soil or- exposure for 14 days (Zhu et al., 2018b), suggesting that collembolans ganisms upon which future human health and well-being depends. are particularly important in the accumulation and dissemination of Finally, as with other environmental contamination, it is urgent to ARGs in soil ecosystems. The accumulation of ARGs in the gut micro- develop frameworks of risk assessment for antibiotics and ARGs in soils, biome of soil fauna (e.g. collembolan) could have an important, but which should include human exposure pathways and risk quantifica- underappreciated, role in the dispersal of ARGs and their transfer tion. Such frameworks shall be developed with the “One Health” per- through the food chain (Fig. 3). spective considering the connectivity of the entire ecosystem. Fauna in soil ecosystems are commonly exposed to multiple stres- sors. Disturbances caused by human activities add to these stressors and can have a major influence on the distribution of ARGs in the gut mi- Declaration of Competing Interest crobiomes of soil fauna. Exposure to silver nanoparticles can sig- nificantly reduce the number and abundance of ARGs in the soil col- The authors declare no competing interests. lembolan gut microbiome (Zhu et al., 2018c), indicating that the effects of pollutants on ARG diversity and abundance are complex. Exploration of the relative influences of different pollutants on the distribution of Acknowledgements ARGs in soil and the gut microbiota of soil fauna should be prioritized in future research, especially for emerging pollutants. We thank many people for helping collect samples. This work was funded by the National Natural Science Foundation of China 5. Perspectives on managing soil biota for planetary health (41571130063), the Strategic Priority Research Program of the Chinese Academy of Sciences (XDB15020302 and XDB15020402) and the Soil and soil fauna microbiomes are the source of bioactive com- National Key Research and Development Program of China- pounds, including antibiotics, which have the diverse and abundant International collaborative project from Ministry of Science and intrinsic resistome. Human activities (e.g. misuse of antibiotics) are Technology (Grant No. 2017YFE0107300). Authors want to specially increasing these resistome and promoting the dispersal of them at the thank MS Hui-Ling Cui for helping in developing the graphs. global scale. The increasing abundance of ARGs in the soil ecosystem has clear and direct implications for planetary health. Management of soil biota – both the microbiota and larger organ- Author contributions isms – is vitally important for safeguarding planetary health. The issues facing such management are multifaceted and involve complex ecolo- Y.G.Z. conceived the manuscript. Y.G.Z., Y.Z. and D.Z. wrote the gies, interactions and evolutionary forces. manuscript. M. G., J. P., Y.S.O., A.C. and S.B. edited the manuscript. 5 Y.-G. Zhu, et al. Environment International 131 (2019) 105059 Fig. 3. Antimicrobials and antimicrobial resistance in the gut microbiomes of soil fauna are linked to human microbiome. References Chen, Q.L., et al., 2018. Effect of biochar amendment on the alleviation of antibiotic resistance in soil and phyllosphere of Brassica chinensis L. Soil Biol. Biochem. 119, 74–82. Abedin, M.J., Cotter-Howells, J., Meharg, A.A., 2002. Arsenic uptake and accumulation in Chen, Q.L., et al., 2019. Antibiotic resistomes in plant microbiomes. Trends Plant Sci. 24, rice (Oryza sativa L.) irrigated with contaminated water. Plant Soil 240, 311–319. 530–541. Adair, K.L., Wilson, M., Bost, A., Douglas, A.E., 2018. Microbial community assembly in Clark, H., 2015. Governance for planetary health and sustainable development. Lancet wild populations of the fruit fly Drosophila melanogaster. ISME J 12, 959. 386, E39–E41. Agamennone, V., Roelofs, D., Van, N.S., Janssens, T., 2018. Antimicrobial activity in Cole, J., Bickersteth, S., 2018. What's planetary about health? An analysis of topics culturable gut microbial communities of springtails. J. Appl. Microbiol. 125, covered in The Lancet Planetary Health's first year. Lancet Planet. health 2, 740–752. e283–e284. Al-Delaimy, W.K., 2018. Planetary health and population health: the anthropocene re- D'Costa, V.M., et al., 2011. Antibiotic resistance is ancient. Nature 477, 457–461. quires different thinking and approaches in serving public health. Curr. environ. De Deyn, G.B., et al., 2003. Soil invertebrate fauna enhances grassland succession and health rep. 5, 397–400. diversity. Nature 422, 711–713. An, X.L., et al., 2018. Tracking antibiotic resistome during wastewater treatment using Devarajan, N., et al., 2015. Accumulation of clinically relevant antibiotic-resistance high throughput quantitative PCR. Environ. Int. 117, 146–153. genes, bacterial load, and metals in freshwater lake sediments in Central Europe. Ashbolt, N.J., et al., 2013. Human Health Risk Assessment (HHRA) for environmental Environ. Sci. Technol. 49, 6528–6537. development and transfer of antibiotic resistance. Environ. Health Perspect. 121, Dromph, K.M., Vestergaard, S., 2002. Pathogenicity and attractiveness of en- 993–1001. tomopathogenic hyphomycete fungi to collembolans. Appl. Soil Ecol. 21, 197–210. Audrain, B., et al., 2015. Role of bacterial volatile compounds in bacterial biology. FEMS Durao, P., Balbontin, R., Gordo, I., 2018. Evolutionary mechanisms shaping the main- Microbiol. Ecol. 39, 222–233. tenance of antibiotic resistance. Trends Microbiol. 26, 677–691. Bahram, M., et al., 2018. Structure and function of the global topsoil microbiome. Nature Fierer, N., 2017. Embracing the unknown: disentangling the complexities of the soil 560, 233–245. microbiome. Nat. Rev. Microbiol. 15, 579–590. Barrios, E., 2007. Soil biota, ecosystem services and land productivity. Ecol. Econ. 64, Food and Agriculture Organization of the United Nations, World Organization for Animal 269–285. Health, World Health Organization, United Nations System Influenza Coordination, Beavington, F., 2000. Foundation work on soil and human health. Eur. J. Soil Sci. 51, United Nations Children's Fund & World Bank, 2008. Contributing to One World, One 365–366. Health: A Strategic Framework for Reducing Risks of Infectious Diseases at the Bengtsson-Palme, J., Kristiansson, E., Larsson, D.G.J., 2018. Environmental factors in- Animal–human– Ecosystems Interface. Available at. http://www.oie.int/downld/ fluencing the development and spread of antibiotic resistance. FEMS Microbiol. Rev. AVIAN%20INFLUENZA/OWOH/OWOH_14Oct08.pdf. 42 (68–80). Forsberg, K.J., et al., 2012. The shared antibiotic resistome of soil bacteria and human Blair, J.M., et al., 2015. Molecular mechanisms of antibiotic resistance. Nat. Rev. pathogens. Science 337, 1107–1111. Microbiol. 13, 42–51. Forsberg, K.J., et al., 2014. Bacterial phylogeny structures soil resistomes across habitats. Broza, M., Pereira, R.M., Stimac, J.L., 2001. The nonsusceptibility of soil Collembola to Nature 509, 612–619. insect pathogens and their potential as scavengers of microbial pesticides. Galán, J.C., Gonzálezcandelas, F., Rolain, J.M., Cantón, R., 2013. Antibiotics as selectors Pedobiologia 45, 523–534. and accelerators of diversity in the mechanisms of resistance: from the resistome to Chain, E., et al., 1940. Penicillin as a chemotherapeutic agent. Lancet 236, 226–228. genetic plasticity in the β-lactamases world. Front. Microbiol. 4 (9). Chen, Q., et al., 2016. Long-term field application of sewage sludge increases the abun- Gillings, M.R., Hagan-Lawson, E.L., 2014. The cost of living in the anthropocene. Earth dance of antibiotic resistance genes in soil. Environ. Int. 92, 1–10. Perspect 1, 2. 6 Y.-G. Zhu, et al. Environment International 131 (2019) 105059 Gillispie, E.C., Sowers, T.D., Duckworth, O.W., Polizzotto, M.L., 2015. Soil pollution due Qiao, M., et al., 2018. Review of antibiotic resistance in China and its environment. to irrigation with arsenic-contaminated groundwater: current state of science. Curr. Environ. Int. 110, 160–172. Pollut. Rep. 1, 1–12. Rizzo, L., et al., 2013. Urban wastewater treatment plants as hotspots for antibiotic re- Goethem, M.W.V., et al., 2018. A reservoir of ‘historical’ antibiotic resistance genes in sistant bacteria and genes spread into the environment: a review. Sci. Total Environ. remote pristine Antarctic soils. Microbiome 6 (40). 447, 345–360. Guzman, J.D., et al., 2012. Antimycobacterials from natural sources: ancient times, an- Roelofs, D., et al., 2013. A functional isopenicillin N synthase in an animal genome. Mol. tibiotic era and novel scaffolds. Front. Biosci. 17, 1861–1881. Biol. Evol. 30, 541–548. Hautbergue, T., et al., 2018. From genomics to metabolomics, moving toward an in- Roquero De Laburu, C., 2000. The agriculture and therefore the soil have played a key tegrated strategy for the discovery of fungal secondary metabolites. Nat. Prod. Rep. role in the history. Anales de la Real Academia de Farmacia 66, 43–61. 35, 147–173. Rusek, J., 1998. Biodiversity of Collembola and their functional role in the ecosystem. Hotopp, J.C.D., et al., 2007. Widespread lateral gene transfer from intracellular bacteria Biodivers. Conserv. 7, 1207–1219. to multicellular eukaryotes. Science 317, 1753–1756. Seltenrich, N., 2018. Down to earth: the emerging field of planetary health. Environ. Hughes, V.M., Datta, N., 1983. Conjugative plasmids in bacteria of the ‘pre-antibiotic’ era. Health Persp. 126, 072001. Nature 302, 725. Sharma, E., et al., 2009. Climate change impacts and vulnerability in the eastern Ikoyi, I., Fowler, A., Schmalenberger, A., 2018. One-time phosphate fertilizer application Himalayas. In: International Centre for Integrated Mountain Development. to grassland columns modifies the soil microbiota and limits its role in ecosystem States, U., 2017. Antibiotic use in the United States, 2017: progress and opportunities. services. Sci. Total Environ. 630, 849–858. Centers for Disease Control and Prevention CDC 24 (7). Insam, H., Gomez-Brandon, M., Ascher, J., 2015. Manure-based biogas fermentation re- Steffan, J.J., Brevik, E.C., Burgess, L.C., Cerda, A., 2018. The effect of soil on human sidues - friend or foe of soil fertility? Soil Biol. Biochem. 84, 1–14. health: an overview. Eur. J. Soil Sci. 69, 159–171. Khan, S., Beattie, T.K., Knapp, C.W., 2016. Relationship between antibiotic- and disin- Su, J.Q., et al., 2017. Metagenomics of urban sewage identifies an extensively shared fectant-resistance profiles in bacteria harvested from tap water. Chemosphere 152, antibiotic resistome in China. Microbiome 5, 84. 132–141. Sultan, I., et al., 2018. Antibiotics, resistome and resistance mechanisms: a bacterial Knapp, C.W., Jan, D., Ehlert, P.A.I., Graham, D.W., 2010. Evidence of increasing anti- perspective. Front. Microbiol. 9. biotic resistance gene abundances in archived soils since 1940. Environ. Sci. Technol. Suring, W., et al., 2016. Biochemical pathways supporting beta-lactam biosynthesis in the 44, 580–587. springtail Folsomia candida. Biol. Open 5, 1784–1789. Knopp, M., Andersson, D.I., 2018. Predictable phenotypes of antibiotic resistance muta- Suring, W., et al., 2017. Evolutionary ecology of beta-lactam gene clusters in animals. tions. mBio 9. Mol. Ecol. 26, 3217–3229. Lambert, P.A., 2005. Bacterial resistance to antibiotics: modified target sites. Adv. Drug Thaiss, C.A., Zmora, N., Levy, M., Elinav, E., 2016. The microbiome and innate immunity. Deliver. Rev. 57, 1471–1485. Nature 535, 65. Larsson, D.G.J., et al., 2018. Critical knowledge gaps and research needs related to the Tong, Z., et al., 2017. Crossed flow microfluidics for high throughput screening of environmental dimensions of antibiotic resistance. Environ. Int. 117, 132–138. bioactive chemical-cell interactions. Lab Chip 17, 501–510. Lavellea, P., et al., 2006. Soil invertebrates and ecosystem services. Eur. J. Soil Biol. 42, Wang, F.H., et al., 2014a. High throughput profiling of antibiotic resistance genes in S3–S15. urban park soils with reclaimed water irrigation. Environ. Sci. Technol. 48, Laxminarayan, R., et al., 2013. Antibiotic resistance—the need for global solutions. 9079–9085. Lancet Infect. Dis. 13, 1057–1098. Wang, F.H., et al., 2014b. Impact of reclaimed water irrigation on antibiotic resistance in Li, G., et al., 2011a. Inorganic arsenic in Chinese food and its cancer risk. Environ. Int. 37, public parks, Beijing, China. Environ. Pollut. 184, 247–253. 1219–1225. Wardle, D.A., et al., 2004. Vulnerability to global change of ecosystem goods and services Li, W.L., et al., 2011b. A novel antimicrobial peptide from skin secretions of the earth- driven by soil biota. In: Sustaining Biodiversity & Ecosystem Services in Soils & worm, Pheretima guillelmi (Michaelsen). Peptides 32, 1146–1150. Sediments. Li, Z., et al., 2014. A review of soil heavy metal pollution from mines in China: pollution World Health Organization, 2015. Global Action Plan on Antimicrobial Resistance. and health risk assessment. Sci. Total Environ. 468, 843–853. Available at: https://www.who.int/antimicrobial-resistance/global-action-plan/en/. Li, G., et al., 2018a. Urban soil and human health: a review. Eur. J. Soil Sci. 69, 196–215. Wright, G.D., 2010. Antibiotic resistance in the environment: a link to the clinic? Curr. Li, J., et al., 2018b. Global survey of antibiotic resistance genes in air. Environ. Sci. Opin. Microbiol. 13, 589–594. Technol. 52, 10975–10984. Xie, W.Y., Shen, Q., Zhao, F.J., 2018. Antibiotics and antibiotic resistance from animal Liu, Y.Q., et al., 2004. Purification of a novel antibacterial short peptide in earthworm manures to soil: a review. Eur. J. Soil Sci. 69, 181–195. Eisenia foetida. Acta Biochim. Biophys. Sin. 36, 297–302. Zeng, M., et al., 2017. Model-based analysis of the long-term effects of fertilization Lorena, B., et al., 2014. A 30-years review on pharmacokinetics of antibiotics: is the right management on cropland soil acidification. Environ. Sci. Technol. 51, 3843–3851. time for pharmacogenetics? Curr. Drug Metab. 15, 581–598. Zhang, Y.J., et al., 2017. Temporal succession of soil antibiotic resistance genes following Maureen, B., et al., 2016. Assembly of the Caenorhabditis elegans gut microbiota from application of swine, cattle and poultry manures spiked with or without antibiotics. diverse soil microbial environments. ISME J 10, 1998–2009. Environ. Pollut. 231, 1621–1632. Nakandalage, N., et al., 2016. Improving rice Zinc biofortification success rates through Zhang, J., et al., 2018. Soil types influence the fate of antibiotic-resistant bacteria and genetic and crop management approaches in a changing environment. Front. Plant antibiotic resistance genes following the land application of sludge composts. Sci. 7 (764). Environ. Int. 118, 34–43. Ochoa-Hueso, R., 2017. Global change and the soil microbiome: a human-health per- Zhang, T., et al., 2019. Time-resolved spread of antibiotic resistance genes in highly spective. Front. Ecol. 5 (71). polluted air. Environ. Int. 127, 333–339. O'neill, J., 2014. Antimicrobial resistance: tackling a crisis for the health and wealth of Zhao, Y., et al., 2018. Feed additives shift gut microbiota and enrich antibiotic resistance nations. Review on Antimicrobial Resistance 1, 1–16. in swine gut. Sci. Total Environ. 621, 1224–1232. Pal, C., et al., 2015. Co-occurrence of resistance genes to antibiotics, biocides and metals Zhao, Y., et al., 2019. Evidence for co-selection of antibiotic resistance genes and mobile reveals novel insights into their co-selection potential. BMC Genomics 16 (964). genetic elements in metal polluted urban soils. Sci. Total Environ. 656, 512–520. Pass, D.A., et al., 2015. The effect of anthropogenic arsenic contamination on the Zhu, Y.G., et al., 2013. Diverse and abundant antibiotic resistance genes in Chinese swine earthworm microbiome. Environ. Microbiol. 17, 1884–1896. farms. P. Natl. Acad. Sci. USA 110, 3435–3440. Perron, G.G., Kryazhimskiy, S., Rice, D.P., Buckling, A., 2013. Multidrug therapy and Zhu, Y.G., et al., 2017. Microbial mass movements. Science 357, 1099–1100. evolution of antibiotic resistance: when order matters. Appl. Environ. Microb. 79, Zhu, D., et al., 2018a. Exposure of soil collembolans to microplastics perturbs their gut 6521. microbiota and alters their isotopic composition. Soil Biol. Biochem. 116, 302–310. Peterson, E., Kaur, P., 2018. Antibiotic resistance mechanisms in bacteria: relationships Zhu, D., et al., 2018b. Antibiotics disturb the microbiome and increase the incidence of between resistance determinants of antibiotic producers, environmental bacteria, and resistance genes in the gut of a common soil collembolan. Environ. Sci. Technol. 52, clinical pathogens. Front. Microbiol. 9. 3081–3090. Prescott, S.L., 2013. Early-life environmental determinants of allergic diseases and the Zhu, D., et al., 2018c. Exposure of a soil collembolan to Ag nanoparticles and AgNO3 wider pandemic of inflammatory noncommunicable diseases. J. Allergy Clin. Immun. disturbs its associated microbiota and lowers the incidence of antibiotic resistance 131, 23–30. genes in the gut. Environ. Sci. Technol. 52, 12748–12756. 7