Sewage Is the Superhighway Spreading Antibiotic Resistance Across the Planet

Antimicrobial resistance has long been framed as a problem of hospitals and overprescription, but a sweeping new review argues that the environment is where much of the real action happens. Writing in Nature Reviews Earth & Environment, an international team led by Liguan Li of The Education University of Hong Kong and Tong Zhang of the University of Hong Kong synthesizes global evidence on how resistance genes emerge, travel and accumulate in ecosystems, and proposes a standardized metagenomic framework for tracking them. Their central conclusion is striking: water, and above all sewage, is the dominant transmission pathway for the bacterial genetic elements that encode resistance, while soil plays a comparatively minor role. That finding reframes environmental resistance not as a diffuse background hazard but as a traceable pollution problem with identifiable sources, and it arrives as the United Nations and the World Health Organization push countries to fold environmental surveillance into their national action plans.

The stakes could hardly be higher. Antimicrobial resistance is now recognized as a major barrier to achieving the Sustainable Development Goals, with landmark assessments warning of a coming microbial crisis in which routine infections and surgeries become dangerous again. The economic projections are sobering, with the World Bank estimating trillions of dollars in cumulative losses if drug-resistant infections continue to rise. Yet the review’s authors emphasize that the clinical view captures only part of the picture. Bacteria have been producing antibiotics and defending against them for hundreds of millions of years, so the genes that neutralize these drugs are ancient and widespread in nature. What has changed is the sheer volume of resistance genes, antibiotics and selective chemical pressure that human activity now pumps into rivers, soils and air, creating conditions in which environmental bacteria and human pathogens can exchange genetic material at an unprecedented rate.

To map where resistance genes actually live, the team turned to metagenomics, the shotgun sequencing of all DNA in an environmental sample. By analyzing global environmental metagenomes across three major sectors, sewage, freshwater and soil, they built a distribution profile of antibiotic resistance genes worldwide. The results give sewage the dubious distinction of being the largest contributor to the environmental resistome, followed by freshwater systems. This makes intuitive sense once the plumbing is considered: sewage concentrates the fecal microbiomes of millions of people, along with the antibiotics they excrete and the disinfectants and heavy metals that co-select for resistance. Wastewater treatment plants remove much of the microbial load, but they are not designed to eliminate resistance genes or residual pharmaceuticals, so treated effluent still delivers a steady drip of genes and selective compounds into receiving rivers and lakes.

The freshwater findings carry particular weight because rivers integrate everything a watershed throws at them. Studies cited in the review show that non-point fecal contamination from aging wastewater infrastructure is a primary driver of resistance in surface waters, and that combined sewer overflows, which release untreated sewage during heavy rain, act as major temporary point sources of resistance genes and multi-resistance risk factors. Sediments of lakes receiving wastewater effluent can become long-term reservoirs of resistance genes, and continental-scale surveys have documented pollution of estuaries on a massive scale. Even the deepest ocean trenches show evidence of anthropogenic resistance gene deposition, while Antarctic soils considered pristine harbor historical resistance genes that predate the antibiotic era. The message is that human influence has reached essentially every aquatic compartment of the planet, and that the hadal trenches and polar soils now serve as archives, and potentially sources, of resistance determinants.

Soil, by contrast, emerges as a comparatively minor player in transmission, which may surprise readers who associate agricultural antibiotic use with environmental resistance. The review does not dismiss soil risks. Manure applications, wastewater irrigation and the application of antibiotic fermentation residues to fields can enrich soil resistomes, and global analyses have linked soil resistance genes to increasing risk and connectivity with the human resistome. But native soil microbial communities appear to provide a buffer, with high diversity and ecological stability acting as a barrier to the accumulation and invasion of resistance genes. Experiments show that resident soil microorganisms can hinder enrichment with resistance genes following manure application. The concern is that agricultural intensification and urbanization homogenize soil microbiomes, eroding exactly that diversity-based resistance and potentially opening the door to wider gene establishment.

The drivers of spread extend well beyond plumbing. The review catalogues an expanding list of anthropogenic and environmental factors that accelerate the movement and evolution of resistance. Air pollution is one of the more provocative: global analyses have associated particulate matter air pollution with clinical antibiotic resistance, and studies suggest that airborne transmission of bacteria and their genes is an underappreciated dimension of the problem. Microplastics add another layer, functioning as novel microbial habitats, so-called plastispheres, where dense, diverse communities can exchange genes more readily; large-scale river analyses have tied urbanization-driven resistance to microplastic-associated communities. Climate change compounds everything, with drought shown to elevate antibiotic resistance across soils, warming reducing microbial diversity in grasslands, and rising carbon dioxide increasing gene transformation rates by altering bacterial membrane channels. Mass gatherings, international travel, wildlife migration and even airplane sewage all contribute to the globalization of resistant bacteria.

At the molecular level, the currency of this trade is the mobile genetic element. Resistance genes rarely travel alone; they ride on plasmids, integrons and transposons, DNA vehicles that can hop between species and genera. The clinical class 1 integron has been described as a pollutant in its own right, a xenogenetic DNA construct that replicates and disperses through food-borne bacteria and wastewater systems. Long-read sequencing studies of cow feces, wastewater host-plasmid networks and single-cell approaches are now revealing which plasmids carry which genes, in which hosts, and how frequently conjugative transfer occurs under different redox and chemical conditions. This mechanistic detail matters because it identifies the choke points: if conjugation in wastewater ecosystems depends on specific redox conditions, then treatment design can target those conditions rather than simply killing bacteria wholesale.

Surveillance is where the review makes its most actionable contribution. The authors argue that systematic monitoring is the key to understanding the evolution and spread of resistance, but they acknowledge a chronic problem: environmental AMR studies use wildly different methods, targets and reporting units, making global comparisons unreliable. Detection pipelines alone can produce large discrepancies in resistome estimates from the same data. To fix this, the team proposes a standardized metagenomic approach built around an integrated surveillance framework with two tiers. A minimal strategy maximizes limited resources to achieve basic surveillance, suitable for regions with constrained laboratory capacity, while a comprehensive strategy allocates resources for in-depth profiling of resistomes, mobilomes and microbiomes. Supporting technologies include absolute quantification using cellular internal standards, universal units for reporting gene abundance, reference materials for calibration, and species-resolved tools such as long-read overlapping and methylation-guided enrichment sequencing that can link resistance genes to specific bacterial hosts.

Policy momentum is already building. The European Union’s recast Urban Wastewater Treatment Directive now requires member states to monitor antimicrobial resistance in wastewater, and the World Health Organization has published guidance for wastewater and environmental surveillance of AMR, including a One Health framework for tracking ESBL-producing E. coli. The review’s authors advocate scaling these efforts into genuinely integrated global surveillance, arguing that characterizing the environmental resistome will identify regional challenges and allow mitigation strategies to be designed rather than guessed at. Mitigation options range from engineering controls, such as upgrading treatment to remove both antibiotics and genes, to ecological interventions that preserve microbial diversity as a natural barrier, to setting no-effect concentrations for antibiotics in the environment based on ecological rather than purely clinical criteria. The authors are candid that inequity remains a central obstacle: low- and middle-income countries, where pollution hotspots are expanding fastest, often lack the resources for even minimal surveillance. Closing that gap, they argue, is not charity but necessity, because resistance genes ignore borders. In a world connected by rivers, air currents and trade, the resistome of one region is ultimately the resistome of all.

Subject of Research: Environmental distribution, surveillance and mitigation of antimicrobial resistance genes

Article Title: Environmental impacts, surveillance and mitigation of antimicrobial resistance

Article References: Li, L., Ding, J., Gillings, M. R., Fatta-Kassinos, D., Manaia, C. M., Berendonk, T. U., Blaser, M. J., Topp, E., & Zhang, T. (2026). Environmental impacts, surveillance and mitigation of antimicrobial resistance. Nature Reviews Earth & Environment. https://doi.org/10.1038/s43017-026-00837-4

Image Credits: AI Generated

DOI: 10.1038/s43017-026-00837-4

Keywords: antimicrobial resistance, antibiotic resistance genes, resistome, metagenomics, wastewater, sewage surveillance, freshwater, soil microbiome, mobile genetic elements, One Health, microplastics, climate change