One Health for humans, animals, plants and ecosystems

Among chemical contaminants from these various activities, pharmaceutical substances are used in human and animal medicine for preventive, therapeutic, or diagnostic purposes. Continuously increasing, their global market reached approximately 1 trillion euros in 2019 (France ranks second in the European market behind Germany¹). This massive production and resulting consumption have harmful environmental consequences, as many of these substances end up being discharged into the environment. The sources of contamination of aquatic environments by pharmaceutical substances are multiple².

A very recent study, covering 1052 sampling sites in 258 rivers across 104 countries spanning all continents, highlighted the global extent of this issue : for over a quarter of the samples, concentrations of pharmaceutical residues exceeded risk thresholds for aquatic organisms³. French aquatic environments are not spared from this contamination from pharmaceutical substances of various families. Among these, certain antibiotics are particularly well represented such as sulfamethoxazole sulfonamide and ofloxacin fluoroquinolone . Data from the water information system (SIE) report that these two substances are quantified in 60% (n=331) and 39% (n=126) of surface water samples, 12% (n=25) and 46% (n=25) of sediment samples, and 47% (n=32) and 45% (n=20) of periphyton samples, respectively⁴. In France, non-steroidal anti-inflammatory drugs (NSAIDs) are also very present in aquatic environments, notably diclofenac, which has been detected in 29% (n=30,029) of surface water samples analyzed between 2007 and 2018⁵.

Widespread contamination of aquatic environments by pharmaceutical substances entails established ecotoxicological risks and effects⁶. While all aquatic organisms can potentially be affected, notably due to the high bioaccumulation of certain substances^7,8, it is relatively accepted that microbial communities are particularly vulnerable to this type of chemical pressure⁶. Their chronic exposure to substances can induce an impact on bacterial and algal diversity and on certain associated ecological functions, posing a risk to the ecological functioning of contaminated ecosystems. This has recently been demonstrated, for example, for antibiotics of the sulfonamide family (including sulfamethoxazole), with periphytic⁹ and sedimentary¹⁰ microbial communities.

However, microbial communities possess significant capacities for adaptation to organic contaminants, including pharmaceutical substances. This can result in tolerance and resistance development . In the case of antibiotics,resistance development is particularly problematic as it raises the issue of the development and spread of antibiotic-resistant bacteria (ARB) and antibiotic resistance genes (ARGs) in aquatic environments. The always increasing use of antibiotics in human activities (medicine, agriculture, etc.) has led to their dispersion into various compartments of aquatic environments. ARB and ARGs have become ubiquitous in ecosystems (especially in periphytic biofilms¹¹ and sediments¹²) with levels of abundance reflecting anthropogenic pressures, notably downstream of WWTP discharges^13. Proliferation of ARB and ARGs in different types of environments has become a major concern, and, according to the WHO could become the leading cause of mortality worldwide¹⁴. Consequently, several authors have raised awareness on the importance of considering the risk of ARB development within natural microbial communities in environmental risk assessment procedures associated with antibiotics^15,16. However, despite frequent questioning, the influence of microbial community exposure to pharmaceutical substances (especially antibiotics) on the selection of ARB and the dispersion of ARGs in aquatic environments remains relatively controversial⁴.

• _{1. IQVIA, 2019. The Global Use of Medicine in 2019 and Outlook to 2023. Forecasts and Areas to Watch. Institute Report.}
• _{2.  Klimaszyk P, Rzymski P, 2018. Water and Aquatic Fauna on Drugs: What are the Impacts of Pharmaceutical Pollution?. In: Zelenakova M (eds) Water Management and the Environment: Case Studies. Doi:10.1007/978-3-319-79014-5_12}
• _{3.  Wilkinson JL et al., 2022. Pharmaceutical pollution of the world’s rivers. PNAS. Doi :10.1073/pnas.2113947119}
• _{4. Anses, 2020. Antibiorésistance et environnement. État et causes possibles de la contamination des milieux en France par les antibiotiques, les bactéries résistantes aux antibiotiques et les supports génétiques de la résistance aux antibiotiques. Avis de l’Anses. Rapport d’expertise collective. 263 p.}
• _{5. Anses, 2019. Avis de l’Anses relatif à l’évaluation des risques sanitaires liés à la présence de diclofénac dans les eaux destinées à la consommation humaine. 59 p.}
• _{6.  Patel M et al., 2019. Pharmaceuticals of Emerging Concern in Aquatic Systems: Chemistry, Occurrence, Effects, and Removal Methods. Chem. Rev. Doi: 10.1021/acs.chemrev.8b00299}
• _{7.  Miller TH et al., 2018. A Review of the Pharmaceutical Exposome in Aquatic Fauna. Environ. Pollut. Doi: 10.1016/j.envpol.2018.04.012}
• _{8.  Bonnineau C et al., 2021. Role of biofilms in contaminant bioaccumulation and trophic transfer in aquatic ecosystems: current state of knowledge and future challenges. Rev. Environ. Contam. Toxicol. Doi :10.1007/398_2019_39}
• _{9. Kergoat L et al., 2021. Environmental Concentrations of Sulfonamides Can Alter Bacterial Structure and Induce Diatom Deformities in Freshwater Biofilm Communities. Front. Microbiol. Doi : 10.3389/fmicb.2021.643719}
• _{10. Pesce S et al., 2021. Contrasting effects of environmental concentrations of sulfonamides on microbial heterotrophic activities in freshwater sediment. Front. Microbiol. Doi :10.3389/fmicb.2021.753647}
• _{11.  Guo XP et al., 2018. Biofilms as a sink for antibiotic resistance genes (ARGs) in the Yangtze estuary. Water Res. Doi: 10.1016/j.watres.2017.11.029}
• _{12.  Calero-Cáceres W et al., 2017.  The occurrence of antibiotic resistance genes in a Mediterranean river and their persistence in the riverbed sediment. Environ. Pollut. Doi : 10.1016/j.envpol.2017.01.035}
• _{13.  Proia L et al., 2016. Occurrence and persistence of antibiotic resistance genes in river biofilms after wastewater inputs in small rivers. Environ. Pollut. Doi :10.1016/j.envpol.2015.11.035}
• _{14.  OMS, 2016. Plan d'action mondial pour combattre la résistance aux antimi- crobiens, Genève, Suisse, 32 p.}
• _{15.  Bengtsson-Palme J, Larsson DG, 2016. Concentrations of antibiotics predicted to select for resistant bacteria: Proposed limits for environmental regulation. Environ. Int. Doi : 10.1016/j.envint.2015.10.015}