Antibiotic Resistance Genes in Food Animal Production: Environmental Implications and One Health Challenges

Abstract

Antibiotics have revolutionized medicine and animal production, yet their extensive use has accelerated the emergence and spread of antimicrobial resistance (AMR). Beyond clinical contexts, livestock and aquaculture are now recognized as major contributors to the global resistome. This review synthesizes evidence across cattle, poultry, swine, sheep and goats, and aquaculture, highlighting how antimicrobial usage shapes resistance at the human–animal–environment interface. A substantial proportion of administered drugs is excreted unmetabolized, leading to the accumulation of unmetabolized antimicrobial residues, antibiotic-resistant bacteria (ARB), and antibiotic resistance genes (ARGs) in soils, manures, waters, sediments, and air. These reservoirs function as long-term sources and dissemination pathways through runoff, leaching, bioaerosols, effluents, and biological vectors. Despite different production systems, similar ARG families dominate, particularly those conferring resistance to tetracyclines, sulfonamides, and β-lactams. Mobile genetic elements and co-selectors such as heavy metals, disinfectants, and microplastics reinforce their persistence. Aquaculture, where water serves both as habitat and vector, emerges as a critical hotspot, while small ruminant systems remain under-researched despite their importance in many low- and middle-income countries. This synthesis highlights convergent patterns across sectors: antimicrobial use drives ARG enrichment; manures, litters, sediments, and effluents act as persistent reservoirs; and dissemination routes connect farms, ecosystems, and human populations. Within a One Health framework, mitigation requires preventive strategies—vaccination, biosecurity, and optimized waste management—supported by harmonized stewardship policies and integrated environmental surveillance.

1. Introduction

The discovery of antibiotics is considered one of the greatest achievements in the history of medicine, drastically extending the average human lifespan and transforming therapeutic possibilities [1]. Since the 1950s, antibiotics have also become a cornerstone of intensive animal production, including aquaculture, creating favorable conditions for both microbial growth and the emergence of resistance [2,3,4]. Industrial farming practices, characterized by high animal densities and prophylactic use of antimicrobials, not only affect animal health but also contribute to the release of antibiotic residues and antibiotic- resistant bacteria (ARB) into the surrounding environment.

Globally, antimicrobial usage in livestock has risen from approximately 63,151 tons in 2010 to nearly 99,502 tons in 2022, with projections exceeding 107,472 tons by 2030 [5,6]. This trend is alarming not only due to the direct risks to human and animal health but also because it strengthens the environmental dimension of AMR. Antibiotics and resistance genes introduced into soils, waters, sediments, and even air constitute long-lasting environmental pollutants, shaping microbial communities beyond farm boundaries. Particularly disturbing is the relationship between the increasing use of antibiotics in animal production and the occurrence of drug-resistant human pathogens [7,8,9]. Antibiotic resistance has become a major threat to therapeutic efficacy in humans using available antibiotics. The problem is multi-faceted because it covers both the medical and economic spheres [10,11]. The increasing ineffectiveness in combating infections caused by ARB is already a global problem [12]. The threat and scale of this phenomenon are demonstrated by analyses predicting that by 2050, incurable bacterial infections will be the most common cause of death, causing over 10 million deaths annually and overtaking cancer and cardiovascular diseases in this respect, with an annual cost to the global economy of 100 trillion US dollars [13]. The World Health Organization [14], Centers for Disease Control and Prevention [15], and Food and Agriculture Organization of the United Nations [16] included microbial resistance to antibiotics and chemotherapeutics among the greatest contemporary public health threats and challenges of the 21st century. The problem is so serious that the dynamics of increasing resistance to antibiotics significantly exceed the pace of developing new antimicrobial preparations [1]. The decline in antibacterial research and development has been ongoing for several decades, with a marked contraction of industrial investment since the 1990s [1]. Many large pharmaceutical companies have withdrawn from antibiotic discovery programs due to the high development costs, low return on investment, and rapid obsolescence of new compounds driven by emerging resistance. As a result, the global clinical pipeline remains alarmingly sparse, dominated by derivatives of existing drug classes rather than novel mechanisms of action. According to the World Health Organization [17] and O’Neill’s global review on antimicrobial resistance [13], this stagnation poses a critical public-health risk, as resistance continues to outpace innovation, leaving few effective treatment options for multidrug-resistant bacterial infections.

The One Health framework recognizes that the interconnections between humans, animals, and ecosystems are central to understanding AMR. Resistant pathogens and resistance genes can circulate through multiple pathways, including food of animal origin, direct occupational exposure, manure and wastewater spreading, or bioaerosols. Microorganisms transmitted through physical contact—e.g., spread by manure, inhalation, or food from vertebrate animals including farm animals—to humans constitute approximately 60% of human pathogens [18,19,20]. Contact with livestock is considered a risk factor for human health, especially among veterinarians, farmers, and aquaculture and slaughterhouse workers, who can be exposed to organisms such as methicillin-resistant Staphylococcus aureus (MRSA), Coxiella burnetii or Lactococcus garvieae [18,21,22,23]. Food of animal origin can also be a source of pathogenic microorganisms [24,25]. In 2022, global meat production amounted to 358.11 million tons, including poultry—139.22 million tons, pig meat—122.59 million tons, beef and buffalo—76.25 million tons, and sheep and goats—16.64 million tons. The average meat consumption was 42.84 kg per year per capita, including poultry—16.94 kg, pig meat—13.89 kg, beef—9.45 kg, and sheep and goat—1.98 kg. Global milk production in 2022 was 930.29 million tons, while the average consumption of milk per person per year, including the milk equivalents of dairy products, was 87.03 kg [26]. According to FAO [27], in 2022 farmed finfish reached 91 million tons, including 79.7 million tons from inland aquaculture and 11.3 million tons from mariculture in the sea and coastal aquaculture on the shore, while their average per capita consumption was 20.7 kg per year. These figures illustrate the global scale of animal-derived food production and highlight the substantial environmental pressures created by intensive agriculture and aquaculture, where antibiotic use and waste discharge contribute to antimicrobial resistance (AMR) dissemination through interconnected pathways involving soils, surface and groundwaters, sediments, and air. Additionally, the increasingly common occurrence of resistance to antimicrobial substances in bacteria is related, among other things, to the occurrence of horizontal gene transfer (HGT) between bacteria, which enables the spread of AMR, including ARGs [2,28]. HGT plays an important role in the spread of both known and new, yet unidentified AMR. The location of antibiotic-resistance genes within mobile genetic elements (plasmids, transposons, integrons) facilitates their dissemination in microbial communities [29]. The interactions between human, animal, and environmental microbial communities are complex and not fully understood, but there is growing evidence linking the use of antibiotics in one microbiota with the occurrence of resistant organisms in another. Environmental reservoirs—including agricultural soils, aquaculture systems, and wastewater effluents—therefore act as amplifiers of AMR, facilitating the exchange of resistance traits between commensal, environmental, and pathogenic bacteria.

2. Materials and Methods

This article represents a review of our contemporary knowledge of the potential dangers to animals, and the environmental effects of their upkeep. The literature was searched between March 2025 and September 2025 in the Google Scholar, Web of Science and Scopus databases using the following entries: AMR, fish, aquaculture, cattle, swine, farming, farming, antibiotics, environment, goat and sheep, small ruminants, poultry, HGT, farm animals, one health, soil, water, genes, spread, runoff, one health framework.

3. AMR in Animal Sector and Aquaculture

3.1. Cattle

Cattle farming, both dairy and beef, represents one of the most important sources of food protein worldwide but is also a recognized hotspot for antimicrobial resistance (AMR). The large scale of antimicrobial use in this sector, combined with the direct environmental release of unmetabolized antimicrobial substances and ARB, positions cattle production as a key contributor to the global burden of antibiotic resistance. Quantified usage data illustrates the magnitude of the problem. A survey of 332 UK dairy farms reported mean antimicrobial consumption of 22.11 per Population Corrected Unit (mg/PCU), with β-lactams and aminoglycosides accounting for the majority of prescriptions [30]. In beef systems, metaphylactic administration of macrolides and lincosamides to prevent bovine respiratory disease (BRD) is widespread, but this has been directly associated with multidrug-resistant Mannheimia haemolytica [31,32,33].

Other pathogens linked to cattle are also commonly resistant. Tetracycline-resistant Escherichia coli has been identified in feces, hides, carcasses, and retail meat products [34,35,36], while plasmid-mediated tetracycline resistance transfer between bovine isolates has been demonstrated experimentally [37]. Vancomycin-resistant Enterococcus spp. have been associated with beef products [38], and livestock-associated MRSA carrying resistance across multiple classes—including penicillins, fluoroquinolones, macrolides, and tetracyclines—have been isolated from cattle and beef environments [39]. Mastitis pathogens illustrate the veterinary importance of resistance. Staphylococcus aureus and Streptococcus uberis isolates from clinical mastitis often exhibit resistance to penicillin, tetracyclines, and erythromycin [40,41], and novel methicillin-resistance determinants in bovine isolates have been described [41,42]. Surveys of E. coli from diseased cattle confirm frequent resistance to ampicillin, streptomycin, sulfonamides, and tetracyclines [43]. Raw milk samples have been shown to carry ARGs encoding multidrug efflux pumps such as norA and mepA, and genes like erm, blaARL, and tet, conferring resistance to macrolides, β-lactams, and tetracyclines [44]. Non-aureus staphylococci isolated from milk also harbor resistance determinants relevant to both animal and human medicine [45]. Environmental dissemination is a defining feature of cattle-associated AMR. Between 40% and 90% of administered antimicrobials are excreted unmetabolized, leaving manure and slurry heavily enriched in active compounds, ARB, and ARGs [29]. When applied to fields, these materials introduce ARGs into soils, where they can persist for months or years. Studies show enrichment of tetracycline and sulfonamide resistance genes, as well as integrons such as intl1, which mediate horizontal gene transfer.

Recent longitudinal monitoring confirmed that three years of cattle manure application significantly increased soil ARGs and integrase gene abundances, underlining the cumulative risk to terrestrial ecosystems [46,47]. Runoff mobilizes these resistance determinants into surface waters, while leaching transfers them to groundwater, creating diffuse environmental exposure pathways. Airborne routes are extending the diffusion even further [48]. Arthropod vectors, particularly flies, have also been shown to carry extended-spectrum β-lactamase (ESBL)-producing E. coli from cattle environments into human settings, bridging the gap between livestock and public health [49]. These findings highlight how cattle farms act as both reservoirs and distribution hubs for AMR, spanning soil, water, air, and vector pathways. Persistence of ARGs is reinforced by their association with mobile genetic elements (plasmids, transposons, integrons) that facilitate horizontal gene transfer across microbial communities. Co-selectors such as heavy metals, pesticides, and disinfectant residues, frequently present in manure and farm effluents, stabilize resistance traits even in the absence of antibiotic pressure [29]. This ecological context ensures that ARGs are not only introduced but maintained and amplified in farm-associated environments. Mitigation strategies have focused on manure management. Aerobic composting and anaerobic digestion can reduce ARG loads, but effectiveness is variable. While reductions in tetracycline and sulfonamide ARGs have been observed, other resistance determinants persist or even increase under composting conditions [50]. Reviews emphasize that manure remains a hotspot for resistance dissemination despite treatment, and that optimized protocols and integrated approaches are needed [51,52]. Preventive herd health measures provide additional leverage. Vaccination against BRD and mastitis pathogens reduces therapeutic antimicrobial needs, while biosecurity improvements—such as improved hygiene, feed controls, and quarantine practices—lower infection pressure. Evidence from dairy herds shows that the route of antimicrobial administration influences resistance development in milk staphylococci, underscoring the role of veterinary practices in shaping farm resistomes [45]. Nevertheless, uptake of vaccines and biosecurity standards is inconsistent across regions, particularly in low- and middle-income countries where regulatory oversight is weak and antimicrobials remain readily accessible. At the global level, significant knowledge gaps remain. Few studies quantify ARG leaching into groundwater or assess long-term impacts on aquatic ecosystems. Comparative research between intensive systems in high-income countries and extensive systems in low- and middle-income countries (LMICs) is limited, leaving important blind spots in understanding global ARG dynamics. A global synthesis concluded that harmonized strategies across soil, water, and air environments are required to mitigate ARG contamination from livestock production, with cattle among the most critical contributors [53].

3.2. Small Ruminants

Sheep and goat farming, particularly in semi-intensive and extensive grazing systems, plays a significant role in rural economies and food security, especially in arid and mountainous regions. These small ruminants are often reared in environments where direct contact with soil, pasture, and water sources increases the opportunities for dissemination of AMR. Although the overall volume of antimicrobial use per animal is lower than in intensive cattle or poultry production, the global scale of small ruminant farming means that these systems represent a non-negligible contributor to the environmental pool of ARGs. Practices such as open grazing, manure deposition on pasture, accumulation of bedding and slurry, and the use of antimicrobials for preventive or therapeutic purposes introduce resistance determinants into surrounding ecosystems. In fragile or overgrazed environments, manure accumulation can accelerate erosion and runoff, further enhancing ARG dispersal and persistence [54]. Antibiotic use in small ruminants varies geographically but shows consistent patterns. A study of 207 sheep farms in the UK reported mean antimicrobial usage of 11.38 mg/PCU, with tetracyclines (57.4%), penicillins (23.7%), and aminoglycosides (10.7%) as the predominant classes. The same analysis indicated a median Defined Daily Doses (DDDvet) of 1.47 and a median Defined Course Doses (DCDvet) of 0.39 per ewe per flock, showing substantial variability between farms depending on production intensity and veterinary practices [55]. These figures, though lower than in cattle or swine, underscore that antimicrobial usage in sheep and goat farming is sufficient to select for resistance. Pathogen surveys illustrate the breadth of resistance. Ecoli isolates from diseased livestock have been reported resistant to ampicillin, streptomycin, sulfonamides, and tetracyclines [43]. Campylobacter jejuni from sheep and goats frequently shows resistance to nalidixic acid, clindamycin, tetracyclines, and azithromycin [56], while Streptococcus dysgalactiae isolated from sheep arthritis cases was resistant to tetracycline [41].

A systematic review of data from Asia, Europe, and Africa found 18 Gram-positive and 13 Gram-negative species from small ruminants resistant to a wide spectrum of antibiotics, including ampicillin, cephalosporins, fluoroquinolones, aminoglycosides, and sulfonamides (N6). Multidrug resistance (MDR) is widespread. In one survey of E. coli isolated from sheep, IncFIB-IncFIC and IncI2 plasmids were identified to co-carry ESBL gene blaCTX-M-55 and the colistin resistance gene mcr-1. These composite plasmids can transfer between different sequence types (STs) in sheep-origin E. coli, and were resistant to almost all tested antibiotics except meropenem [57]. Other studies report Acinetobacter baumannii from sheep meat resistant to streptomycin, gentamicin, co-trimoxazole, tetracycline, and trimethoprim [58], and methicillin-resistant S. aureus (MRSA), mupirocin-resistant S. epidermidis, and multi-resistant Macrococcus caseolyticus and Enterococcus faecium in goat meat [59]. Environmental dissemination pathways are critical in small ruminant systems. Manure deposition during grazing, as well as the collection and spreading of manure for fertilization, serve as significant reservoirs of ARGs. Studies have shown that manure and feed by-products such as rapeseed cake significantly alter soil microbial communities and increase the relative abundance of resistance genes [60]. Soils amended with sheep or goat manure act as ARG reservoirs, with potential for transfer across the soil–plant continuum and indirect exposure of humans via crops [51]. Runoff from grazing lands or fertilized pastures mobilizes resistance determinants into surface waters, while infiltration pathways can transfer ARGs into groundwater, especially in fragile or overgrazed ecosystems [61]. Other factors further influence persistence. Residual antibiotic compounds in sheep and goat manure can sustain selection pressures on soil microbiota, while microplastics present in manure and bedding waste provide surfaces for biofilm growth, favoring horizontal gene transfer between ARB [28]. Heavy metals, sometimes used as nutritional supplements, act as co-selectors stabilizing ARGs in microbial communities even in the absence of direct antimicrobial exposure. Together, these factors amplify the environmental role of small ruminant production systems in ARG dissemination. From a One Health perspective, sheep and goat farming connects to human health through multiple routes. Farm workers and veterinarians are exposed directly to resistant pathogens such as MRSA and resistant enterococci [59]. Consumers may encounter resistant strains through contaminated meat and milk products, as demonstrated by the detection of MDR S. aureus and resistant Acinetobacter in retail meat [57,58]. Environmental routes are equally important: ARGs released into soils and waters may contaminate irrigation systems, crops, and downstream ecosystems. In extensive grazing systems, small ruminants may also serve as bridges between domestic livestock and wildlife microbiomes, facilitating the exchange of ARGs across species boundaries. Despite these findings, knowledge gaps remain. Surveillance of antimicrobial use in sheep and goats is far less systematic than in cattle, poultry, or swine, and data from low- and middle-income countries—where small ruminants play a major role in rural food security—are particularly scarce. Environmental monitoring of ARG persistence in soils, waters, and runoff under extensive grazing is fragmented, and the long-term stability of ARGs in these ecosystems is not well understood. The role of vectors, such as insects, in disseminating ARB from small ruminant systems has scarcely been investigated. Taken together, these results demonstrate that sheep and goats, although often underrepresented in AMR studies compared to cattle, swine, or poultry, contribute meaningfully to the environmental dissemination of resistance. Their production environments, grazing practices, and manure management facilitate ARG persistence and spread into soils, waters, crops, and wildlife.

3.3. Poultry

Poultry is the most widely consumed type of meat globally, accounting for approximately 35% of total meat consumption and representing one of the fastest growing sectors of animal protein production. The scale and intensity of poultry farming make it a critical node in the global discussion on antimicrobial resistance, not only because of its direct relevance to human food safety, but also because of the environmental implications of antibiotic use in high-density animal production [62,63]. Antibiotics are commonly administered in poultry not only to treat or prevent disease, but also to enhance growth rates and improve egg-laying performance [64]. The most frequently used classes include β-lactams, tetramisole, quinolones and fluoroquinolones, tetracyclines, and coccidiostats [65]. Such practices have contributed to the widespread emergence of multidrug-resistant (MDR) bacteria that circulate between birds, humans, and the environment. One of the most concerning phenomena is the global dissemination of MDR Salmonella, frequently detected in poultry meat, eggs, and egg products. These isolates are often resistant to streptomycin, spectinomycin, sulfonamides, chloramphenicol, florfenicol, tetracyclines, and β-lactams, making them a persistent public health threat [62,65,66]. Van den Bogaard et al. [67] showed that broilers had significantly higher levels of resistance genes against quinupristin/dalfopristin and vancomycin than laying hens, indicating that the intensity of production directly influences the AMR profile. Beyond Salmonella, other pathogens linked to poultry farming—such as Campylobacter spp., Enterococcus spp., E. coli, and Staphylococcus aureus—are also frequently multidrug resistant and play an important role in zoonotic transmission [66]. Campylobacter spp., for example, colonize the intestinal mucosa of poultry and remain viable under diverse storage conditions; isolates tested in recent studies showed high resistance rates to nalidixic acid, ampicillin, cephalexin, ciprofloxacin, erythromycin, gentamicin, and tetracycline. Similarly, Enterococcus species, natural members of the avian gut microbiota and common contaminants of poultry meat, have been shown to resist aminoglycosides, doxycycline, tetracyclines, and quinolones [62,68,69].

Beyond the direct risks to consumers and occupationally exposed workers, poultry farming significantly contributes to the environmental dissemination of antimicrobial resistance genes. Poultry litter, a mixture of excreta, bedding, feathers, and feed residues, is one of the most important vehicles of ARG release. It is widely used as fertilizer because of its nutrient value, yet it often contains antibiotic residues, ARB, and mobile genetic elements. Application of poultry litter to fields alters soil microbial communities and has been associated with the persistence and enrichment of clinically relevant resistance determinants, including blaTEM, blaSHV, qnr genes, and class 1 integrons [70]. Studies have demonstrated that resistance genes can persist in soils for extended periods following litter application, and in some cases may be transferred to plant-associated microbiota, raising concerns about indirect human exposure via crops [71,72]. Runoff from litter-amended fields can further mobilize ARGs into surface water and groundwater, contributing to their accumulation in aquatic ecosystems [73]. The environmental dimension of poultry production also includes the release of bioaerosols. Intensive farms generate dust and aerosols rich in ARB and ARGs, which disperse into the surrounding atmosphere and can be inhaled by farm workers or nearby communities. Recent research has confirmed that poultry house aerosols contain ARGs at levels comparable to those found in litter, with some evidence of long-distance dispersal under favourable meteorological conditions [74]. The occupational health risks for farm workers, and the potential for ARG dissemination beyond farm boundaries, highlight bioaerosols as an often-underappreciated route of AMR spread. Another important consideration is the geographic and management-dependent variation in AMR dynamics. Comparative studies indicate that ARG prevalence in poultry production environments differs between regions, influenced by differences in antibiotic regulation, farm management, and biosecurity practices [75]. In some low- and middle-income countries, weak enforcement of antimicrobial regulations exacerbates the problem, leading to higher environmental loads of resistance genes and residues [76]. Meanwhile, evidence from longitudinal field studies suggests that although some soil microbiomes exhibit resilience and partial recovery after repeated manure applications, others retain elevated ARG abundances over time, indicating long-term ecological shifts and potential feedback loops between poultry production and environmental health [77].

3.4. Swine

Swine production is one of the most important and intensively managed sectors of animal agriculture, accounting for nearly 25% of global protein consumption and close to 30% of all meat production. The industry is geographically concentrated, with more than 60% of production in Asia and China as the dominant producer. Antimicrobial use in swine is among the highest across livestock species, driven by intensive husbandry, rapid growth cycles, and susceptibility of swine to infectious diseases. Historically, antibiotics were used as growth promoters in swine diets, and although such practices have been banned in the European Union since 2006, prophylactic, metaphylactic, and therapeutic uses remain widespread in many regions. These practices make swine systems a major reservoir and amplifier of AMR, with direct implications for human health through the food chain and through multiple environmental dissemination pathways. Patterns of antibiotic usage in swine reflect the sector’s intensity. A Chinese survey reported that over 90% of E. coli isolates from pig farms were MDR, with particularly high resistance to tetracyclines, chloramphenicol, fluoroquinolones, and sulfonamides, while lower but still significant resistance was observed for critically important drugs such as colistin and carbapenems [78]. A UK study of pig farms identified 144 distinct ARGs in farm microbiomes, dominated by resistance determinants to tetracyclines, macrolides (tylosin), and trimethoprim [79]. Other investigations have confirmed the widespread occurrence of ARGs in swine feces, slurry, and meat products, including blaCTX-M, β-lactamases, mcr-1 colistin resistance genes, vanA vancomycin resistance, sul1/sul2 sulfonamide resistance, tet(A)/tet(B) tetracycline resistance, and cat chloramphenicol resistance [80,81,82]. Importantly, swines are recognized reservoirs of livestock-associated MRSA (LA-MRSA), which have been transmitted to humans in direct contact with swine, such as farmers, veterinarians, and abattoir workers [21]. The magnitude of antimicrobial inputs into swine production translates directly into environmental burdens. It is estimated that 30–80% of administered antibiotics are excreted unmetabolized in pig feces and urine, creating a manure stream heavily contaminated with active drug residues, ARB, and ARGs [5]. This manure is commonly stored in lagoons or applied to agricultural fields as fertilizer, where it functions as a major ARG reservoir. Soil resistomes in fields fertilized with pig slurry consistently show higher abundances of tetracycline, sulfonamide, and macrolide resistance genes compared to unfertilized controls [83]. Longitudinal monitoring demonstrates that manure application increases ARG prevalence and diversity in soil microbiomes, and some resistance determinants persist for years. Horizontal gene transfer mediated by plasmids, transposons, and integrons ensures that resistance spreads across environmental microbial communities, creating the potential for transfer into opportunistic and pathogenic bacteria.

Runoff and leaching connect pig farming to aquatic environments. Studies have identified sulfonamide and tetracycline resistance genes in surface waters downstream of pig farms, and ARGs have been traced into groundwater beneath manure storage lagoons. In addition to aquatic dissemination, bioaerosols generated during pig housing ventilation and manure handling can disperse ARB and ARGs into the surrounding atmosphere. Air samples collected downwind of pig barns have yielded tetracycline- and macrolide-resistant E. coli and staphylococci, demonstrating airborne transmission potential [84]. Arthropods such as houseflies and cockroaches also serve as vectors, transporting ARB from swine facilities into human habitations [85]. Together, these findings show that swine systems distribute resistance traits across multiple environmental compartments—soil, water, air, and vectors. Several studies highlight the scale and complexity of the swine resistome [5,21,77,78,79,80,81,82,83,84,85]. Metagenomic sequencing of pig manure and farm soils consistently detects thousands of ARG subtypes, with efflux pumps and β-lactamases dominating the gene pool [86]. Notably, ARGs in pig manure are frequently co-located with mobile genetic elements such as class 1 integrons, facilitating rapid spread. Environmental co-selectors exacerbate persistence. Copper and zinc are often used in pig feed as growth promoters, and these metals exert strong selective pressure on microbial communities, stabilizing resistance determinants even when antibiotic use is reduced [87]. Similarly, microplastics in manure and effluents provide surfaces for biofilm formation, promoting horizontal gene transfer between ARB [88]. Global differences in usage intensity and stewardship are reflected in the environmental resistome. In Europe, restrictions on antibiotic use have lowered antimicrobial inputs on pig farms, but environmental surveillance shows that ARGs persist in soils and manures long after reductions in drug use, indicating the resilience of environmental resistomes [89]. In contrast, in many low- and middle-income countries, prophylactic antibiotic use remains common, growth promoters are often still used, and manure treatment infrastructure is minimal, creating conditions for extensive ARG dissemination [7].

This imbalance creates global public health risks, as ARGs selected in poorly regulated settings can spread through international trade and ecological flows. Mitigation strategies are under active study but remain unevenly adopted. Composting and anaerobic digestion of pig manure reduce ARG loads, but persistence of specific resistance genes remains a recurring challenge [90]. Advanced treatments such as biochar amendment and constructed wetlands can improve removal, but scalability is uncertain. Preventive approaches are critical. Vaccination programs targeting swine bacterial pathogens and enhanced biosecurity measures reduce infection pressure and lower antibiotic demand [91]. However, cost, infrastructure, and farmer compliance limit their adoption in many settings. Knowledge gaps are evident. Long-term field studies quantifying the impact of reduced antimicrobial use on soil and water resistomes are scarce. The relative importance of airborne vs. waterborne vs. vector pathways in ARG dissemination remains unresolved. Few studies address the ecological impacts of swine ARG pollution on microbial biodiversity, nutrient cycling, or wildlife health. Emerging analytical tools—high-throughput metagenomics, resistome-wide qPCR panels, and computational reservoir modeling—offer promise for quantifying ARG flows across farm environments, but their use in swine systems remains limited to research projects.

3.5. Aquaculture

Aquaculture is the fastest growing source of animal protein globally and is projected to surpass capture fisheries in supplying fish for human consumption [27]. According to the FAO State of World Fisheries and Aquaculture 2024, global aquaculture production reached 91 million tons in 2022, with an average annual growth rate of about 4.7% since 2010. Inland aquaculture accounted for approximately 87% of global farmed finfish output, while mariculture contributed the remainder, reflecting the sector’s continuing expansion toward both freshwater and marine systems [27]. While essential for meeting the food demands of a growing population, this rapid intensification carries a serious risk: it is increasingly recognized as a major hotspot for AMR. Unlike land-based farming, aquaculture operates in open or semi-closed aquatic environments where the same water that supports fish health also serves as a vehicle for the transport of antimicrobial residues, antibiotic-resistant bacteria (ARB), and ARGs. This dual role of water makes aquaculture uniquely vulnerable to AMR emergence and dissemination. It also means that resistance generated within farms does not remain isolated but can rapidly spread into surrounding ecosystems, creating broad environmental and public health consequences. Pathogens of greatest concern in aquaculture include Aeromonas hydrophila, A. salmonicida, Vibrio anguillarum, V. harveyi, Flavobacterium psychrophilum, Citrobacter freundii, Pseudomonas fluorescens, Yersinia ruckeri, Piscirickettsia salmonis, and Tenacibaculum maritimum. Among these, A. hydrophila is particularly dominant in freshwater systems [8]. Therapeutic interventions typically involve tetracyclines, quinolones, β-lactams, and sulfonamides [4,8]. However, bacterial diseases caused by P. salmonis and T. maritimum have become among the most critical drivers of antimicrobial use in global aquaculture, which are associated with ulcerative skin lesions and gill necrosis in marine fish such as Atlantic salmon and rainbow trout, leading to high mortality rates [92]. In Chile, infections caused by P. salmonis account for the majority of antibiotic consumption in salmon farming [93]. Due to the limited effectiveness of available vaccines and the persistence of these pathogens in the marine environment, farmers rely on antimicrobials such as florfenicol and oxytetracycline for disease control frequently [94]. Nevertheless, antibiotic delivery in water is highly inefficient: fish often absorb only a fraction of the administered dose, with 40–90% of compounds entering the surrounding environment unmetabolized. This imposes selective pressure on both pathogenic and non-pathogenic microbiota and has led to the rise in MDR bacteria such as Aeromonas, Pseudomonas, Acinetobacter, Lactococcus, and Edwardsiella [4,95]. The accumulation of antibiotic residues and resistance genes in sediments and aquatic ecosystems further exacerbates the problem. These MDR strains complicate disease management on farms and in some cases pose zoonotic risks to farm workers and consumers.

The environmental consequences of aquaculture antibiotic use are increasingly well documented. Studies in the Baltic Sea showed sulfonamide and trimethoprim resistance genes accumulating in sediments beneath fish cages [96]. Lin et al. demonstrated that ARGs can be transferred not only via water and sediments but also through biofilms and aquatic organisms, highlighting multiple interconnected pathways [97]. Zhou et al. confirmed that aquaculture is not a closed system: ARGs and resistant microbiota move between human wastewater inputs and fish farms, reinforcing one another [98]. Even recirculating aquaculture systems (RAS)—widely promoted as sustainable—were found to harbor ARGs against sulfonamides, macrolides, cephalosporins, and β-lactams despite operating without direct antibiotic use [99]. This suggests that once ARGs are established, they can persist and cycle within aquatic microbiomes independent of ongoing antimicrobial exposure. A major concern is the persistence of ARGs in sediments, which function as long-term reservoirs. Metagenomic surveys have identified thousands of ARG subtypes in aquaculture pond sediments dominated by efflux pump and β-lactamase resistance genes [100,101]. Environmental drivers such as nitrogen loading, organic enrichment, and low dissolved oxygen further influence ARG abundance and stability. ARG-contaminated sediments can release resistance elements back into the water column during resuspension events, extending their impact beyond the farm environment. Moreover, rivers that receive municipal and livestock effluents and subsequently feed aquaculture ponds are already enriched with critical resistance determinants such as blaCTX-M [102], blaNDM [103], mcr [104], tet(X) [105], and vanA [106].

This interconnection means aquaculture does not only generate AMR but also acts as a recipient and amplifier of upstream resistomes. Production systems vary widely in their risk profiles. In net-pen systems, antibiotics, ARB, and ARGs disperse rapidly into surrounding waters, sediments, and benthic communities, where they accumulate and impact wild fish populations [96,97]. Flow-through Pond systems, dominant in Asia and Latin America, accumulate residues locally but discharge nutrient- and ARG-rich effluents downstream, often without treatment, making them important regional hotspots. In contrast, RAS facilities, though reducing external discharge, still develop biofilm-rich resistome hotspots in filters and sludge basins that foster ARG persistence; periodic backwashing or sludge removal can release these ARGs unless effluents are stabilized [99,107]. Newer models such as integrated multi-trophic aquaculture (IMTA), combining fish with algae and shellfish, have been proposed as more sustainable, as filter feeders can reduce organic loads, yet evidence of their effect on ARG dissemination is limited. This diversity of systems underscores the need for system-specific monitoring and tailored management strategies. Effluents are thus a central point of concern. Untreated farm outlets transport antibiotics, ARB, and ARGs directly into rivers, estuaries, and coastal zones. Evidence shows significant overlap between aquaculture effluents and municipal wastewater resistomes, particularly in regions where sewage treatment is minimal [98,101]. This overlap manifests in shared sulfonamide and β-lactam resistance markers and integrons, suggesting that aquaculture, municipal sewage, and agriculture reinforce one another in common watersheds. In many low- and middle-income countries (LMICs), aquaculture facilities discharge untreated effluents, amplifying ARG proliferation, while in high-income countries stricter effluent regulation mitigates—but does not eliminate—the risks. A comprehensive monitoring strategy must therefore include inlet water, farm outlets, sediments, and biofilms to capture the full resistome footprint [100,101,107].

Quantitative monitoring indicates that antibiotic concentrations in some aquaculture effluents frequently approach or exceed predicted no-effect concentrations (PNECs) for resistance selection, particularly for oxytetracycline, sulfamethoxazole, and florfenicol, with measured values ranging from low nanograms to several micrograms per litre in farm discharges [108,109]. These findings suggest that even environmentally relevant concentrations can maintain selective pressure on aquatic microbiota and promote horizontal gene transfer. Effluent reuse represents an additional concern: in certain regions, nutrient-rich aquaculture water is redirected for crop irrigation or incorporated into aquaponic systems, providing a potential route for ARG uptake by soil and plant microbiomes [110]. Integrating PNEC-based thresholds into monitoring frameworks and evaluating effluent reuse practices would therefore strengthen risk assessments and inform future regulatory guidance for sustainable aquaculture operations within a One Health context.

The ecological harms extend far beyond resistant pathogens. ARG enrichment alters microbial communities, destabilizing ecosystem functions such as nutrient cycling, organic matter decomposition, and primary productivity. In benthic habitats beneath cages, the enrichment of ARB and organic deposition alters community structure, threatening biodiversity. ARGs and ARB ascend aquatic food webs, colonizing wild fish, invertebrates, and shellfish, and can move into terrestrial systems when aquaculture effluents are used for crop irrigation. This indirect pathway highlights that populations far removed from seafood consumption may still be exposed to aquaculture-derived ARGs. Ecosystem service impacts are significant: compromised microbial processes reduce water quality regulation and resilience to eutrophication, while resistant pathogens in wild fish may affect fisheries and food security. In ecologically sensitive areas such as coral reefs, lagoons, and freshwater lakes, the persistence of ARGs and ARB represents an additional stressor compounding climate change and overfishing pressures. Additional drivers amplify ARG dissemination. Microplastics, abundant in aquaculture environments, adsorb antibiotics and bacteria, serving as microhabitats for horizontal gene transfer [28]. Heavy metals, often included in aquafeeds or introduced through upstream runoff, act as co-selectors that stabilize ARGs even when antibiotic pressure decreases. Viral vectors such as bacteriophages may further mediate gene transfer, though their role remains understudied. These ecological stressors interact to reinforce ARG persistence, illustrating that AMR in aquaculture is shaped by broader environmental conditions, not solely by antibiotic usage. From a management perspective, reducing antibiotic use at the source is the most effective strategy. Vaccination is a cornerstone: commercial vaccines have reduced antimicrobial demand in salmon farming, and autogenous vaccines provide tailored solutions where licensed products are lacking [111]. Biosecurity frameworks for aquaculture, now increasingly standardized, provide preventive protocols to limit disease introduction and spread [112]. Governance, however, remains uneven. While Europe and North America have moved toward stewardship programs, harmonized thresholds, and surveillance, many LMICs lack regulatory oversight, allowing routine prophylactic use and untreated effluent discharge [113]. End-of-pipe solutions such as wetlands, biofilm reactors, and UV/ozone treatments reduce ARGs in effluents but cannot remediate entrenched sediment reservoirs. Long-term sustainability therefore depends on preventive measures: vaccination, biosecurity, improved water quality, optimized stocking densities, and strict bans on critically important antibiotics [108]).

In summary, aquaculture is uniquely positioned as a major environmental contributor to AMR because of its reliance on water, which ensures high connectivity between farms, ecosystems, and human populations (Figure 1). Sediments and effluents act as long-term ARG reservoirs, reinforced by co-selectors such as metals, plastics, and phages, while overlapping with municipal wastewater resistomes magnifies dissemination.

3.6. Mitigation Strategies

Mitigating antimicrobial resistance (AMR) in livestock and aquaculture requires coordinated, cross-sectoral interventions that reduce antimicrobial inputs, interrupt dissemination pathways, and strengthen governance. Evidence from terrestrial and aquatic systems shows that preventive approaches—rather than end-of-pipe remediation—deliver the most durable reductions in resistance [53,108,109,112].

Vaccination is a cornerstone of prevention that can lower the need for therapeutic interventions and thereby diminish environmental contamination. In cattle, herd-level preventive strategies, including immunization against respiratory and mastitis pathogens, are part of integrated programs that limit the need for antimicrobial treatments [94]. Comparable benefits are reported in swine where vaccination against Actinobacillus pleuropneumoniae and enterotoxigenic Escherichia coli forms a key component of antimicrobial-sparing management [91,94], in poultry flocks vaccinated against Eimeria spp. and bacterial respiratory agents [62,66], and in aquaculture systems employing commercial or autogenous vaccines to control Piscirickettsia salmonis, Aeromonas hydrophila, and A. salmonicida [95,111,112]. Despite their value, uptake remains uneven in low- and middle-income countries (LMICs) because of costs, infrastructure limitations, and cold-chain constraints [7,52].

Enhanced biosecurity is equally essential for minimizing infection pressure and antimicrobial use. Standard measures—including controlled animal movement, quarantine, routine disinfection, vector and pest control, and management of stocking densities—curb pathogen transmission in both terrestrial and aquatic systems [91,108,112]. In cattle and swine, husbandry and hygiene practices shape AMR dynamics—with evidence that certain feed additives (e.g., high zinc) can increase the proportion of multidrug-resistant E. coli, underscoring the need for careful management [87], and that transmission between animals, humans, and the environment is facilitated under suboptimal sanitary conditions [34,69]. In poultry, proper litter handling and ventilation reduce the bioaerosol-mediated spread of resistance genes [74,75,84], while in aquaculture, water-quality management and biosecurity protocols decrease the need for chemotherapeutic treatments [95,99,112]. These measures work best when coupled with farmer training, veterinary oversight, and economic incentives that offset up-front infrastructure costs [7,81,87].

Because 30–90% of administered antimicrobials are excreted unmetabolized, animal wastes and effluents are major environmental reservoirs of antibiotic residues, antibiotic-resistant bacteria (ARB), and antibiotic-resistance genes (ARGs) [50,53]. Optimized manure and wastewater treatment—via aerobic composting, anaerobic digestion, biochar amendment, thermophilic processing, and, where appropriate, constructed wetlands or UV/ozone disinfection—can markedly reduce ARG loads, although complete removal is rare [50,51,90]. Composting decreases tetracycline- and sulfonamide-resistance genes [90], whereas biochar and wetland polishing improve ARG removal from effluents [50,97]. Nevertheless, sediments and soils repeatedly amended with animal wastes retain legacy resistomes for years, arguing for prevention at the source rather than reliance on downstream technologies [50,53,83].

Effective antimicrobial stewardship remains the most direct route to limit resistance emergence. Regulatory frameworks such as the European Union’s ban on antibiotic growth promoters and mandatory veterinary prescriptions have reduced veterinary antimicrobial sales while maintaining productivity [81,89]. Extending similar policies globally—especially enforcing bans on critically important antimicrobials for human medicine such as colistin and carbapenems—would yield major public-health benefits [14,62,82]. Harmonized surveillance integrating antimicrobial-usage data, resistance profiles, and environmental monitoring enables comparisons across regions and early detection of emerging threats [5,6,14,53,109]. In settings with weak governance, practical incentives and international support are needed to achieve compliance [7,52].

Because resistance stability is reinforced by non-antibiotic co-selectors, mitigation must also address heavy-metal additives, disinfectant residues, and microplastics that promote biofilm formation and horizontal gene transfer [46,47]. Re-evaluating copper and zinc supplementation in feeds, prioritizing targeted rather than routine disinfection, and reducing plastics in farming and aquaculture facilities can collectively diminish ancillary selection pressures [47,87]. Comprehensive surveillance should span manure, soils, sediments, effluents, air, and arthropod vectors, using standardized indicators such as intI1 and representative ARG panels for cross-sector comparability [49,70,74].

Critical knowledge gaps persist regarding groundwater contamination beneath manure-storage lagoons, the decay rates of ARGs following reductions in antimicrobial use, and the ecological effects of ARG enrichment on microbial diversity and nutrient cycling [21,50,53,90]. Expanding long-term monitoring in under-studied systems—small-ruminant farming and small-scale aquaculture, particularly in LMICs—remains a priority [7,54,95].

Overall, evidence supports a hierarchy of action: prevent infection through vaccination and biosecurity; minimize antimicrobial inputs via stewardship and regulation; manage wastes and effluents to reduce environmental dissemination; and control co-selective pressures that stabilize resistance. Implemented within a One Health framework linking veterinary practice, environmental management, and public health, this integrated approach offers a realistic pathway to reduce the AMR footprint of global food production while preserving animal welfare and productivity [14,52,109].

4. Discussion

AMR in food animal production is increasingly recognized not only as a clinical or veterinary issue but as a pervasive environmental phenomenon with global implications. The evidence synthesized across cattle, swine, poultry, sheep and goats, and aquaculture reveals a striking convergence of patterns despite wide heterogeneity in production intensity, biosecurity, and geography: the same resistance gene families repeatedly emerge, accumulate in similar environmental reservoirs, and spread through overlapping dissemination routes that link farms to ecosystems and human populations [109,110]. This convergence indicates that AMR arising in food systems is systemic rather than sector-specific and therefore requires cross-sectoral solutions consistent with One Health principles.

Across species and regions, antimicrobial usage remains the central driver of resistance selection, yet the drug portfolios differ by sector (

Table 1. Presence of ARB, ARGs, and MGEs in food animal sectors.

Food Animal Sector	Representative ARB	Key ARGs	Representative MGEs	Type of Resistance Mediated	References
Cattle	M. haemolytica, E. coli, S. uberis, MRSA, Enterococcus spp.	blaCTX-M, blaARL, erm, tet(A/B/C), mcr-1, norA, mepA, aadA, sul1, VanA	Conjugative plasmids (IncF, IncI1), integrons (intl 1), transposons (Tn916- Tn1545)	Macrolides, lincosamides, β-lactam, tetracycline, colistin, fluoroquinolones, sulfonamide resistance	[29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49]
Small ruminants (sheep/goats)	S. aureus, C. jejuni, Enterococcus spp., E. coli	blaCTX-M, erm(B), tet(A/B/C), aac(6′)-aph(2″), sul, mcr-1, VanA	Plasmids (IncI2, IncFIB-IncFIC), transposons (Tn1545), integrons	Macrolide, tetracycline, β-lactam, aminoglycoside, colistin, sulfonamide resistance	[54,55,56,57,58,59,60]
Poultry	Salmonella spp., C. jejuni, E. coli (ESBL), Enterococcus spp., S. aureus	blaTEM, blaSHV, qnrS, tet(A/B/C), erm(B), qnr, sul2, VanA	IncI1/IncK plasmids, class 1 integrons, IS26 transposase	β-lactam, Cephalosporin, quinolone, tetracycline, macrolide, sulfonamide resistance	[61,62,63,64,65,66,67,68,69,70,71,72,73,74]
Swine	E. coli, Salmonella spp., E. faecalis, MRSA	blaCTX-M, mecA, erm(B), tet(M), aadA2, floR, sul1, VanA, mcr-1	SCCmec cassette, Tn916, IncI1/IncI2 plasmids, class 1 integrons	β-lactam, macrolide, tetracycline, amphenicol, Fluoroquinolones, sulfonamide resistance	[5,7,21,76,77,78,79,80,81,82,83,84,85,86,87,88,89]
Aquaculture	A. hydrophila, Vibrio spp., Pseudomonas spp., Edwardsiella tarda, Lactococcus garvieae	tet(A/B), qnrS, sul1, floR, catA, blaCTX-M, blaNDM, mcr, VanA	Plasmids (IncQ, IncP), integrons, gene cassettes, ISCR elements, Tn1721 transposase	Tetracycline, quinolone, sulfonamide, chloramphenicol, β-lactam resistance	[4,8,27,90,91,92,93,94,95,96,97,98,99,100,101,102,103,104,105,106,107,108,109]

). In cattle, β-lactams, aminoglycosides, and macrolides dominate; in swine and poultry, tetracyclines, sulfonamides, macrolides, and fluoroquinolones are prominent; in small ruminants, tetracyclines and penicillins predominate; and in aquaculture, tetracyclines, sulfonamides, β-lactams, and quinolones are common [5,115,116]. Despite these distinctions, environmental monitoring consistently recovers the same core resistance determinants: tetracycline (tet) and sulfonamide (sul1/sul2) genes and β-lactam resistance (including ESBLs such as blaCTX-M), with carbapenemases (blaNDM), plasmid-mediated colistin resistance (mcr- family), and glycopeptide resistance (vanA) now repeatedly detected outside clinical settings [114,117,118,119,120]. These ARGs are not isolated entities but rather functional components embedded in the bacterial genome or MGEs such as plasmids, transposons, integrons and bacteriophages. The host microorganisms and the genetic environment in which these ARGs are located determine their mobility, expression and persistence within the microbial community. For instance, the ARGs carried by plasmids are usually associated with a wide range of host plasmids (such as IncP, IncQ or IncF), promoting HGT between bacteria living in animal intestines, soil and aquatic systems [114]. Integrons (notably intI1) and transposons (such as Tn196, Tn1545), further enhance this mobility by capturing and rearranging the gene box, promoting the rapid assembly of multidrug resistance determinants [29,120]. Furthermore, an increasing amount of evidence highlights the role of bacteriophages as reservoirs and carriers for the spread of ARGs in both aquatic and terrestrial environments, and they contribute to the expansion of resistance groups even in the absence of direct antibiotic pressure [121]. Because selection and transfer operate in parallel, the global resistome becomes interconnected, and local usage decisions can have transboundary impacts via shared watersheds, wildlife movement, and trade.

Environmental reservoirs are remarkably consistent across terrestrial and aquatic production systems. In cattle, swine, and poultry, manure and slurry are the primary repositories of unmetabolized antimicrobials and ARB; their application to fields introduces ARGs into soils, where they can persist for months to years and shift community composition [122,123]. Repeated poultry-litter applications intensify this effect, elevating soil ARG abundance and altering microbial networks well beyond single seasons [124]. In aquaculture, sediments beneath cages and ponds act as functional analogues, accumulating ARGs and antibiotic residues that can be resuspended into the water column through storm events, benthic disturbance, or routine farm operations [94]. Water is the universal connector: runoff and leaching transfer terrestrial ARGs to surface waters, while aquaculture effluents discharge resistomes directly into receiving waters [125]. In many low- and middle-income countries (LMICs), where wastewater treatment is limited, overlap between farm effluents and municipal wastewater resistomes is common, creating feedback loops that reinforce ARG circulation across sectors [126]. Beneath manure storage and lagoons, the groundwater pathway remains under characterized and is likely under-recognized as a long-term sink and source of ARGs [127]. Beyond soil and water, bioaerosols from barns and manure application, together with insect vectors such as flies, extend dissemination into the near-farm atmosphere and nearby settlements, a route still under-integrated in surveillance [49,128].

The resistant pathogen landscape reflects these environmental dynamics and differs in emphasis by sector while sharing common themes. In cattle, mastitis-associated Staphylococcus aureus and Streptococcus uberis frequently display resistance to penicillin, tetracyclines, and macrolides, and fecal or beef E. coli and Enterococcus often carry multidrug resistance [129]. Swine systems repeatedly yield resistant E. coli and livestock-associated MRSA; tet(A), sul1/sul2, blaCTX-M, and mcr-1 are widely reported in slurry and feces [130]. Poultry amplifies resistant Salmonella, Campylobacter, Enterococcus, and E. coli; fluoroquinolone resistance in Campylobacter and E. coli is particularly consequential for human therapy [53]. In sheep and goats, resistant S. aureus, Campylobacter, and Acinetobacter are documented but surveillance is sparse, especially in LMICs despite the sector’s nutritional importance [95]. Aquaculture adds resistant Aeromonas, Vibrio, Flavobacterium, Pseudomonas, and Acinetobacter that overlap with terrestrial resistomes, underscoring aquatic–terrestrial connectivity [4,42]. Across all sectors, livestock-associated MRSA exemplifies a zoonotic hazard that bridges animal management, environmental persistence, and human exposure [127].

The ecological consequences of resistome enrichment extend beyond infection risk. Elevated ARG abundance can restructure microbial communities, weakening the key ecosystem functions such as organic-matter decomposition, nitrogen and phosphorus cycling, and primary productivity [126]. In soils, altered microbial networks may affect crop performance and disease suppressiveness; in aquatic sediments, changes in benthic community composition can ripple through food webs and impair carbon sequestration [131]. Evidence of spillover to wildlife—for example, resistant E. coli and Enterococcus in wild birds or fish—indicates that agricultural resistomes can permeate natural communities, complicating conservation and biosecurity [132]. These ecological effects rarely occur in isolation: eutrophication, warming, hypoxia, and chemical co-contaminants co-select with antibiotics, creating reinforcing feedback that stabilizes ARGs even when direct antimicrobial inputs decline [133]. Co-selectors include heavy metals in feeds, disinfectants in housing, and microplastics acting as vectors and biofilm substrates; bacteriophages may mediate gene transfer but remain under-studied in farm environments [85,134]. The implication is that AMR pressures are woven into broader environmental change, and mitigation must address these coupled drivers rather than antimicrobial use alone.

Global comparisons highlight divergent trajectories. In the European Union, the 2006 ban on antibiotic growth promoters and subsequent stewardship programs have reduced veterinary antimicrobial sales, yet legacy ARGs persist in soils and sediments, indicating long residence times and slow decay in environmental compartments [135,136]. In China, which leads global pig and aquaculture production, high antimicrobial inputs persist despite new regulations; river basins downstream of intensive production frequently show enriched ARG profiles, illustrating basin-scale connectivity [137]. In South America, intensive poultry production and salmon aquaculture (notably Chile) contribute to regional ARG hotspots, reflecting heavy reliance on prophylaxis during disease-prone growth phases [138]. In parts of Africa, limited veterinary oversight and easy over-the-counter access to antimicrobials, coupled with unmanaged manure use, create conditions for resistome amplification in smallholder systems; data gaps here are substantial, complicating regional risk assessment [7]. These disparities mean that while high-income regions grapple with legacy contamination and targeted stewardship, LMICs often face ongoing amplification and limited infrastructure for manure and effluent treatment, with international trade and shared hydrology connecting both realities.

Socio-economic drivers help explain why technical solutions are unevenly adopted. Global demand for abundant, low-cost animal protein exerts pressure to maintain productivity; antimicrobials can buffer management deficits and disease risk, especially where veterinary access is limited [139]. Retailer policies and consumer pressure have pushed partial reductions in some high-income markets, but incentives and subsidies for preventive health and waste-management infrastructure are often lacking in LMICs [140]. Without aligning economic signals with public-health goals, stewardship competes against short-term production imperatives.

Governance and monitoring likewise remain uneven. The EU’s regulatory framework (growth-promoter ban, veterinary prescription, European Surveillance of Veterinary Antimicrobial Consumption (ESVAC) monitoring) demonstrates that policy can shift market behavior and usage patterns [141]. At the global level, the WHO Global Action Plan, the FAO/WOAH/WHO One Health collaboration, and Codex guidance articulate stewardship and surveillance principles, but implementation varies widely and comparable data remain scarce outside Europe and North America [142]. Even where usage declines, environmental resistomes may not quickly follow because entrenched reservoirs in soils and sediments persist and can reseed water and biota [132]. Thus, surveillance must extend beyond sales/usage metrics to systematic environmental monitoring of manures, soils, sediments, effluents, bioaerosols, and vectors, adopting harmonized indicators (e.g., intI1, sentinel ARG panels) to enable cross-country comparability [120,127].

From the perspective of practical control, the weight of evidence favors prevention over remediation. Vaccination reduces disease incidence and antimicrobial demand; mastitis vaccines in cattle and autogenous vaccines in aquaculture provide sector-specific examples where licensed products are scarce or pathogen diversity is high [111]. Biosecurity—stocking density, water and air hygiene, feed quality, and movement controls—lowers pathogen pressure, but adoption is uneven and sensitive to farm economics. For wastes, composting, anaerobic digestion, and biochar amendments lower but rarely eliminate ARG burdens; performance depends strongly on temperature regime, residence time, and feedstock composition [142]. In aquaculture, constructed wetlands and biofilm reactors reduce effluent microbial loads but do not remediate legacy sediments already seeded with ARGs [107]. The emerging consensus is that reducing antimicrobial inputs, improving welfare, optimizing densities, and vaccinating are more effective and durable than relying on end-of-pipe technologies alone [107,111,135,141]. Because co-selectors sustain ARGs independent of antibiotic use, stewardship must be coupled with metal management, disinfectant policies, and plastic mitigation in production environments [87,133,134,135].

Several research priorities follow logically from this synthesis. First, quantify groundwater pathways and residence times beneath lagoons and storage structures to close a persistent surveillance gap [127]. Second, disentangle the ecological consequences of ARG enrichment—on biodiversity, biogeochemical cycling, and ecosystem services—through field experiments and long-term observations [114,116,120,121]. Third, extend surveillance in small ruminants and small-scale aquaculture in LMICs, where data are sparse but population exposure is high [7,8]. Fourth, determine resistome decay rates after usage reduction under real farm conditions to guide realistic expectations for stewardship benefits [135]. Finally, integrate airborne and vector-borne routes into routine monitoring, as these underappreciated pathways bridge farm boundaries and communities [49,127,128].

Taken together, the evidence shows that livestock and aquaculture act simultaneously as reservoirs and amplifiers of resistance. Antimicrobial use drives selection of ARGs at the farm scale; environmental reservoirs stabilize and propagate them; and dissemination via soil, water, air, and biota connects production sites to ecosystems and human populations. Because drivers and pathways are shared across sectors, integrated strategies—antimicrobial stewardship aligned with economic incentives, preventive animal health, improved manure and effluent treatment, harmonized environmental surveillance, and coordinated international governance—are required to meaningfully reduce the contribution of food production to the global AMR burden [142]. Without such coordination, entrenched environmental reservoirs will continue to reseed resistance even as usage falls; with it, sustainable protein production is compatible with protecting human health and ecosystem resilience (

Table 2. Comparison of differences and similarities in the selective generation of AMR and its spread across various industries.

Aspect	Cattle	Small Ruminants (Sheep/Goats)	Poultry	Swine	Aquaculture
Main antimicrobial use	Therapeutic and metaphylactic treatments for mastitis, respiratory and enteric infections	Preventive or therapeutic use against pneumonia and footrot	Routine prophylaxis in intensive systems; feed additives in some regions	High usage for growth promotion and prophylaxis in intensive farming	Mixed in feed or water to prevent bacterial diseases
Mechanisms of resistance generation	HGT in gut and manure microbiota	HGT among commensal and pathogenic bacteria in mixed herds	Plasmid and integronmediated resistance	Co-selection through mobile genetic elements in gut microbiota	HGT in biofilm-associated bacteria and sediments
Environmental reservoirs	Manure, slurry, and pasture soils	Manure and grazing areas	Litter, dust, and runoff from poultry houses	Manure lagoons and contaminated soils, microplastics in manure and effluents	Sediments, water columns, and biofilms
Routes of AMR spread	Manure application to fields, milk waste, farm runoff, airborne routes, arthropod vectors	Open grazing, manure deposition, bedding and slurry accumulation	Airborne dust, litter disposal, food chain	Manure application to fields, Airborne dust, arthropod vectors, contact with workers, meat contamination	Effluent discharge (fish farms-human wastewater), fish trade, and bioaerosols
Public health relevance	E. coli, Salmonella, Staphylococcus aureus, Streptococcus uberis	Campylobacter, Staphylococcus spp., Macrococcus caseolyticus, Enterococcus faecium, MRSA	Salmonella, Campylobacter, Enterococcus	E. coli, Salmonella, Yersinia, LA-MRSA	Aeromonas, Vibrio, Pseudomonas, Flavobacterium, Acinetobacter, Lactococcus, Edwardsiella
References	[30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53]	[54,55,56,57,58,59,60,61]	[62,63,64,65,66,67,68,69,70,71,72,73,74,75,76,77]	[5,7,78,79,80,81,82,83,84,85,86,87,88,89,90,91]	[4,8,27,92,93,94,95,96,97,98,99,100,101,102,103,104,105,106,107,108,109,110,111,112,113]

).

5. Conclusions and Perspectives

Livestock and aquaculture systems are clear reservoirs and amplifiers of AMR, with tetracycline, sulfonamide, and β-lactam resistance genes dominating across species. Manures, litters, effluents, and sediments act as long-term reservoirs, releasing ARGs into soils, waters, and air, while dissemination is reinforced by bioaerosols, vectors, and co-selectors such as heavy metals and microplastics. These pathways confirm that AMR is not only a clinical or veterinary challenge but a pervasive environmental issue directly linking farming practices to ecosystem health and human exposure. Despite extensive research, key gaps remain. The long-term persistence of ARGs in groundwater and sediments, their ecological impacts on biodiversity and ecosystem services, and the underrepresentation of small ruminant systems and low- and middle-income countries in surveillance remain pressing blind spots. The most effective interventions are preventive: vaccination, biosecurity, and improved husbandry to reduce antimicrobial demand, combined with optimized manure and effluent management. End-of-pipe technologies may mitigate emissions but cannot remove entrenched reservoirs. Looking forward, a One Health approach is essential. Coordinated international stewardship, harmonized monitoring indicators, and integration of veterinary, environmental, and public health policies are needed to curb the environmental spread of resistance.

To move forward, research should prioritize systematic monitoring in low- and middle-income countries where surveillance is scarce but livestock dependence is relatively high, long-term studies on the persistence and decay of ARGs in groundwater and sediments as overlooked reservoirs, and studies on the role of biological vectors such as insects in bridging farm and community resistomes. Without such interventions, livestock and aquaculture will continue to drive global resistome enrichment.