The discovery of penicillin marked the beginning of modern medicine (Hutchings et al., 2019), which has led to antibiotics being used as a basic method of treating diseases in people and animals for decades (Xie et al., 2018). The expansion of large-scale animal production systems has raised the demand for veterinary antibiotics, which are used not only to treat infections but also to prevent disease and promote growth. Many veterinary antibiotics are supplied in animal feed at subtherapeutic levels to promote growth (Gonzalez Ronquillo and Angeles Hernandez, 2017; Caneschi et al., 2023). However, many antibiotics are excreted intact or as active metabolites because they are not entirely absorbed (Tiedje et al., 2023). Antibiotic use in farm animals creates an environment that promotes the formation of antibiotic-resistant bacteria (ARBs), which spread through manure and the surrounding ecosystem.

Agricultural soil is crucial to preserving food security and ecological balance. It is a critical resource for crop production, influencing crop yield, quality, and environmental health. The United Nations Sustainable Development Goals (SDGs) emphasize the need for sustainable agricultural practices in ensuring food security, especially considering the world’s growing population and the increasing constraints of climate change. Among the many challenges confronting agricultural systems, antibiotic contamination poses a significant threat to soil health and food safety, raising concerns about the emergence of antibiotic-resistance genes (ARGs) in agricultural ecosystems. The SDGs, particularly goal 2, seek to eliminate hunger, ensure food security, and promote sustainable agriculture by 2030. This goal acknowledges that sustainable agriculture is critical to ensuring food security and promoting nutrition. However, the presence of antibiotics in agricultural soils, commonly caused by manure application and the use of wastewater for irrigation, affects this goal. The widespread use of antibiotics in livestock farming has resulted in the accumulation of these substances in the environment, which can harm soil microbiota and disrupt essential soil functions like nutrient cycling and organic matter decomposition (Udikovic-Kolic et al., 2014; Christou et al., 2017; Checcucci et al., 2020). Beneficial microbes that have developed resistance can spread through the food chain to humans through the consumption of affected crops (Pepper et al., 2018; Lima et al., 2020; Fatoba et al., 2021). Studies have demonstrated manure to be a hotspot for spreading ARGs, promoting horizontal gene transfer among soil bacteria (Deng et al., 2024; Wang S. et al., 2024). Antibiotics in soil alter microbial community structure and functional capabilities, potentially reducing soil fertility and increasing vulnerability to pests and diseases (Yang et al., 2016; Cycon et al., 2019). The persistence of these antibiotics in the soil is affected by environmental factors such as soil type, pH, and organic matter content, thereby affecting their bioavailability and degradation (Li et al., 2022; Liu et al., 2022b; Cui et al., 2023). Antibiotic resistance spreading through the food chain is a major public health concern, as infections caused by resistant bacteria are often more challenging to treat, resulting in increased morbidity and mortality (Han et al., 2022; Elder et al., 2023). Hence, there is a critical need for integrated methods to address antibiotic usage in agriculture, promote sustainable farming techniques, and protect soil health to secure food for future generations.

One of the sustainable solutions to combat this issue is the use of beneficial microbes. Beneficial microbes offer an environmentally friendly and sustainable solution for detoxifying antibiotics in agricultural soil. The effect of the increased concentrations of these antibiotics on soil microbial abundance, diversity, and communities, as well as microbial functions and processes in the soil, can be ameliorated by microbial bioremediation. In relation to antibiotic stress, beneficial microbes have been reported to improve soil health and alleviate plant stress through various mechanisms, such as siderophore production, biotransformation, biosorption, and biodegradation. Many soil contaminants, including antibiotics, pesticides, heavy metals, oil spillage, etc., have been biodegraded using beneficial microbes. For instance, the bacterium Cupriavidus metallidurans strain MSR33 has demonstrated significant potential in remediating mercury-contaminated soils, showing the ability to tolerate heavy metals and positively influence the nitrogen cycle in the soil ecosystem (Bravo et al., 2020). In another study by Xu J. et al. (2021), engineered strains were developed to enhance the degradation of p-nitrophenol through specific enzymatic pathways, which are crucial for breaking down complex organic molecules. Therefore, beneficial bacteria can be used to mitigate the effects of these contaminants. In addition to their bioremediation properties, they help improve soil and plant health, promoting plant growth and improving food security (Olanrewaju et al., 2017, 2024a).

Since the increased accumulation of antibiotics on agricultural soil is fast becoming a cause for serious concern because of their detrimental effect on soil microbiome and their role in increasing antibiotic resistance, it is of paramount interest to find a way to alleviate these impacts using an eco-friendly and sustainable approach. Keeping this in mind, this review attempts to present an environmentally sustainable approach to mitigating the effects of these antibiotics on agricultural soil, soil microbial community, and, ultimately, plant health.

When animal-administered antibiotics find their way into the soil through manure application, they place greater pressure on ARG selection because of their prolonged stay in the soil. Although they are in small doses, the impact of the duration of exposure on ARG and the microbiome is more adverse than their impact on animals because the duration of exposure in animals is short. Studies have been conducted to show the effects of antibiotic exposure to ARGs in soil, for example, a study by Zhu et al. (2013), investigates the prevalence of ARGs in soils associated with large-scale Chinese swine farms. Using a high-throughput quantitative PCR, the study reported 149 unique ARGs, many significantly enriched compared to control soils, with fold increases reaching as high as 28,000. Similarly, studies have shown that using antibiotics in livestock creates selective pressures that favor the proliferation of resistant bacteria, leading to increased ARG abundance in fecal matter (Storteboom et al., 2010). The continuous application of antibiotics in agriculture selects resistant strains and facilitates horizontal gene transfer among microbial communities, amplifying the spread of resistance traits (Gromala et al., 2021; Larsson and Flach, 2022).

Manure is often nutrient-rich and serves as a reservoir for various antibiotics, which can significantly influence the soil microbiome. Studies have shown that introducing manure into soil can increase the abundance of ARGs, as these genes can be transferred among microbial populations through horizontal gene transfer mechanisms. For instance, the study by Zhu et al. (2019) demonstrated that the trophic transfer of ARGs occurs within soil detritus food chains, indicating that organisms feeding on manure can acquire these resistance genes, amplifying their presence in the soil microbiome. Furthermore, Negreanu et al. (2012) noted that while the application of manure with high levels of ARBs initially increases resistance in the soil microbiome, this resistance often returns to baseline levels within six months, suggesting a dynamic equilibrium influenced by environmental factors and microbial interactions. The persistence and spread of ARGs in soil are influenced by various factors, including the type of manure applied and the microbial community structure. Hilaire et al. (2022) found that subsurface manure injection can reduce the surface transport of ARGs but may create localized hotspots of resistance within the soil. This phenomenon underscores the complexity of manure application practices and their varying impacts on soil health. Additionally, Xu H. et al. (2021) highlighted the role of soil bacteria as carriers for plasmids that harbor ARGs, facilitating their transmission to plant endophytic bacteria, which can further propagate resistance within plant microbiomes. This interaction between soil and plant microbiomes is crucial, as it can lead to the establishment of resistant strains in crops, posing potential risks to food safety and human health.

The soil microbiome itself is significantly affected by manure application, which can alter microbial diversity and community composition. Banerjee and Heijden emphasized that urban soil microbiomes often contain higher levels of ARGs and genes associated with human pathogens, likely due to anthropogenic influences such as manure application (Banerjee and van der Heijden, 2023). The introduction of manure can enhance microbial diversity, as reported in the study by Sun et al. (2021), which reported that manure application introduced specific resistance genes to surface soils, thereby reshaping the microbial landscape. This alteration in microbial communities can have cascading effects on soil health, nutrient cycling, and plant interactions, ultimately influencing agricultural productivity. The impact of manure-derived ARGs on plant health is a critical area of concern. Research indicates that ARBs in the soil can affect plant growth and health, potentially leading to reduced crop yields. Muurinen et al. (2017) reported that while manure application does not permanently alter the resistance profile of soils, the cyclic changes in the resistome can affect plant health over time. Similarly, Jauregi et al. (2021) also reported that the mobility of antibiotic resistance from manure to soil and vegetable microbiomes is a significant risk factor, as it can lead to the contamination of food crops with resistant pathogens. This highlights the need for careful management of manure application to mitigate risks associated with antibiotic resistance in agricultural systems. Environmental factors and management practices further complicate the dynamics of ARGs and ARBs in manure-amended soils. For example, Wang E. et al. (2024) noted that long-term manure application can change bacterial communities in the rhizosphere, which may influence plants’ uptake of contaminants such as heavy metals and pathogens. This interaction between soil microbiomes and plant health is critical, as it can determine the overall resilience of agricultural systems to stressors such as disease and nutrient deficiencies. Additionally, heavy metals in manure can exacerbate the risks associated with antibiotic resistance, as these metals can co-select for resistant strains.

Besides manure application, antibiotics can be introduced into agricultural soil through irrigation. About 70% of freshwater globally is being used for irrigation, meaning that water demand will increase in the near future (Sharma et al., 2020). This has made wastewater irrigation a valuable resource for water shortage, especially in developing countries, and this may be more common in the near future (Tian et al., 2021). Although wastewater irrigation offers positive advantages as it contains nutrients important for soil fertility and plant health, it also contains pollutants (Kodesova et al., 2024), including heavy metals (Ahmed et al., 2023; Ugulu et al., 2024) and antibiotics (Mehanni et al., 2023; Mohy et al., 2023), which are environmental risks. Antibiotics in wastewater can increase the dominance of ARBs through selective pressures and horizontal gene transfers (Guo et al., 2017). Therefore, this poses a health risk to humans as these strains can be acquired through the food chain. As a matter of concern, reported exposure to ARBs through the food chain from agricultural soils irrigated (Rahman et al., 2021; Geng et al., 2022).

The soil consists of diverse microbial communities, and bacteria have been reported to be the most abundant (Olanrewaju et al., 2017). Bacteria carrying ARGs are also present in the soil. However, the introduction of antibiotics through manure application and wastewater irrigation systems, albeit in small concentrations, for a prolonged period, exerts selective pressure on the soil microbiome (Banerjee and van der Heijden, 2023). In response, as a survival mechanism, the soil microbial community develops resistance to these antibiotics to protect itself. This increases the presence of ARBs and ARGs in the soil microbiome. In addition, the manure and wastewater can carry ARBs and ARGs, which are directly transferred to agricultural soil (Mohy et al., 2023; Zhang Y. et al., 2023). Hence, although beneficial to plant growth, these activities are key to disseminating ARBs and ARGs in agricultural soil. However, studies of the potential spread of antibiotic resistance in the environment have mostly focused on the evolution of antibiotic resistomes in soil and wastewater, with little attention paid to the subsequent spread of antibiotic resistance via plant microbiomes. Many studies have investigated the potential dissemination of antibiotic resistance in the environment (including agricultural soil and wastewater) using qPCR, genomics, metatranscriptomics, and metagenomics (D'angelo, 2023; Ferreira et al., 2023; Kim et al., 2023; de Farias et al., 2024; Molale-Tom et al., 2024; Olanrewaju et al., 2024b,c). This indicates the urgent need for proper waste disposal and recycling for sustainable agriculture (Chen et al., 2019).

Soil microbiomes enter the plant endosphere through the root surface. The plant consists of the endosphere and the ectosphere. The endosphere is inside the plant tissues, while the ectosphere is further categorized into the plastisphere (leaf surface), the capisphere (fruit surface), and the rhizosphere (root surface). The most affected plant compartments in the agricultural fields are the rhizosphere, plastisphere, and capisphere, depending on irrigation and manure application. The microbiome in soil finds its way to the rhizosphere, and when the microbiome is abundant in ARBs, these also make their way to the rhizosphere. Likewise, ARBs in irrigation wastewater are attached to the plastisphere and capisphere, the plant’s above-ground parts. Irrigation affects above-ground and below-ground plant compartments, while manure application affects the below-ground part because it is applied directly to the soil. The entry of the microbial community from the ectosphere into the endosphere provides a transfer route for ARBs and ARGs from manure and wastewater to the soil and the plants (Scaccia et al., 2021). This has been reported in many studies, for example, according to the study by Xu H. et al. (2021), soil bacteria can transfer plasmids harboring ARGs to plant endophytic bacteria, especially those belonging to the phylum Proteobacteria, which contains a variety of plant and human pathogens. This transfer risks human health and agricultural output by making these pathogens more antibiotic-resistant and virulent. These transfers have significant ramifications, indicating that soil management techniques may unintentionally contribute to the spread of antibiotic resistance in agricultural systems. In addition, the composition of the soil microbiome plays a crucial role in determining the health of plants (Banerjee and van der Heijden, 2023). The initial soil microbiome was reported on plant health (Wei et al., 2019), with shifts in microbial communities occurring due to root exudates that alter the microbial landscape. Therefore, the soil microbiome’s initial state can influence the types of bacteria that colonize the plant endosphere, including those that may carry ARGs.

Upon entering plants, these ARBs and ARGs can further find their way into humans through consumption. Although the direct transfer of ARBs and ARGs from plants to humans has not been fully substantiated, this possibility is very high, especially in leafy vegetable crops such as spinach, lettuce, etc., which are often consumed uncooked or partially cooked. Even when washed, the endosphere remains unaffected. Hence, antibiotic-resistant endosphere bacteria in the vegetables can be problematic when ingested by humans. Apart from causing issues, they can also transfer ARGs to the human gut microbiome through horizontal gene transfer (HGT) via plasmids and mobile genetic elements (MGE) (Rossi et al., 2014; Mafiz et al., 2021). This is a big cause for alarm from one health perspective because studies have shown that consumption of these vegetables is a possible route of ARGs from the soil microbiome to humans (Zhang Y. J. et al., 2019; Mafiz et al., 2021; Rahman et al., 2021). In addition, apart from taking up ARBs, plants can also take up antibiotics directly from the soil amended with manure or irrigated with wastewater (Azanu et al., 2016; Gu et al., 2021; Tadic et al., 2021), which may also exert selection pressure on the plant endosphere microbiome and increase the possibility of the development of a more resistant microbiome, which can be transferred to humans upon consumption. Due to its findings in many studies, the class I integron gene (intI1) and genes encoding transposases are common in harvested vegetables (Freitag et al., 2018; Urra et al., 2019; Zhang Y. J. et al., 2019; Yuan et al., 2022), indicating the possibility of HGT in the phyllosphere. The phyllosphere and rhizosphere may be key areas for HGT in plant and soil habitats because of the high possibility that cells cluster, forming biofilms in the phyllosphere, and bacterial metabolic rates and the mobility of bacteria and MGEs are high in rhizospheres (Chen et al., 2019). Using a functional metagenomic screen of soil-inhabiting bacteria, a significant nucleotide identity (>99%) was observed between resistance cassettes in multidrug-resistant bacteria from soil and those in human pathogens from clinical environments, indicating the occurrence of HGT between these microorganisms (Forsberg et al., 2012). In the screen, two class 1 integrase genes (intI1) from the soil bacteria and clinical pathogens were adjacent to the ARGs, facilitating a shared mechanism of HGT between these two bacterial groups. Class 1 integrons, containing the gene intI1, play an essential role in integrating multiple ARGs on the same genetic locus, generating multidrug resistance in bacterial genomes. The integrons have been observed as prevalent carriers of multiple ARGs in natural and anthropogenically influenced environments (Guo et al., 2017). Based on a study with archived soils, manure applications substantially increased the abundance of soil intI1 (Urra et al., 2019).

The interplay between soil microbiomes, agricultural practices, and human health reveals a critical need to rethink soil and plant management approaches. Harnessing beneficial microbes presents a viable, environmentally sustainable solution to counteract the spread of antibiotic resistance while improving plant productivity. The subsequent discussion focuses on the promising role of these microbes in fostering agricultural sustainability.

Antibiotic residues from manure and wastewater often persist in soils at sub-inhibitory levels that both select for resistant bacteria and elevate horizontal gene transfer, including conjugative plasmid transfer across environmental microbiomes. Laboratory work shows that sub-MIC exposures to aminoglycosides, carbapenems, fluoroquinolones, and cephalosporins increase conjugation frequencies, mechanistically supporting resistance exchange at environmental concentrations below MICs. Related studies report fluoroquinolone-driven, dose-dependent increases in RP4 plasmid transfer from E. coli to P. aeruginosa at sub-MICs, highlighting a realistic pathway for ARG dissemination under low-level exposures (Ding et al., 2022). Beyond antibiotics, heavy metals common in agri-food systems (Cu, Zn, Hg, Cd) act as co-selectors that stabilize and enrich ARG-bearing elements even when antibiotic concentrations are low, reinforcing persistence across soil-crop-animal-human interfaces (Shun-Mei et al., 2018). Field evidence from raw-wastewater-irrigated agriculture shows soils with elevated transferable ARGs, including ESBLs, and community functional shifts, documenting an environmental conduit consistent with the mechanistic data (Bougnom et al., 2020).

Actionable implications follow directly. First, benchmark effluents and manures against predicted no-effect concentrations (PNEC) for resistance selection thresholds, which are typically lower than ecotoxicity PNECs; compound-specific PNEC resistance values have been proposed to guide emission limits (Bengtsson-Palme and Larsson, 2016). Where antibiotic-specific data are lacking, a default target of 0.05 μg L⁻¹ has been recommended for antibiotics to minimize selection pressure (Vestel et al., 2022). Second, treated manures in multi-omics field trials show composting reduces total ARGs and resistome risk relative to raw manure, although marker-specific exceptions warrant reporting treatment stage and verifying with sentinel ARGs (Keenum et al., 2021). Together, source control (including co-selectors), evidence-based waste handling, and targeted surveillance at high-risk nodes operationalize a one health response that links mechanistic insight to practical mitigation in agricultural landscapes (Bougnom et al., 2020).

The behavior and fate of antibiotics in the environment are not only determined by their physicochemical properties, which include volatility, lipophilicity, water solubility, and sorption capacity, but also determined by various environmental factors, including the different soil properties such as pH, ionic strength, organic matter content, and cation exchange capacity, and the ecological climatic conditions (Figure 2). As a result of these factors, antibiotics can remain in the environment for a short or extended period. Understanding these interactions is essential in assessing the environmental impact of antibiotic residues, particularly in agricultural settings.

Bacterial bioremediation can help clean antibiotic-polluted farm soils, but it has significant regulatory and practical challenges. Tight rules on genetically modified organisms (GMOs), different ways to manage antibiotics, and ecological uncertainties make deployment tricky. Practical challenges like microbial survival, cost-effectiveness, and soil variability limit scalability. Hence, we examine barriers, highlighting their impact on microbial solutions and the need for integrated strategies to realize the bioremediation potential of beneficial bacteria.

Regulatory frameworks for antibiotic use and microbial bioremediation vary widely from country to country and region to region, creating uneven landscapes for implementation. In the European Union (EU), strict regulations, such as Regulation (EU) 2019/6, have banned antibiotic growth promoters in livestock since 2006 (Topp et al., 2018; Mdegela et al., 2021; Farrukh et al., 2025). However, therapeutic use remains high, with 131 mg/kg of poultry biomass treated annually, maintaining ARG hotspots (Checcucci et al., 2020). In regions like South Asia and parts of Africa, lax oversight allows subtherapeutic dosing, with up to 70% of veterinary antibiotics excreted unchanged, boosting soil ARG loads by 10³ copies/g (Muhammad et al., 2020). This disparity hampers consistent bioremediation strategies, as bacterial strains face different antibiotic pressures in their immediate environments.

Also, the regulations surrounding genetically modified organisms impose additional constraints on using CRISPR-edited bacterial strains. The European Union’s Directive 2001/18/EC categorizes CRISPR-modified strains as GMOs (Okoli et al., 2022), necessitating extensive risk assessments and public approval processes. This affects the benefits of this technology. For example, the field trials of Pseudomonas with a silenced intI1 gene were postponed, notwithstanding the success observed in laboratory settings (Ferreira et al., 2023). On the other hand, the USDA’s streamlined process under the “SECURE Rule” permits certain gene-edited microbes to bypass GMO labeling in the United States, provided that no foreign DNA is present. This facilitates pilot tests of Bacillus subtilis that have been enhanced with the tetX gene (Kim et al., 2023). In developing nations, it is evident that regulatory frameworks frequently exhibit significant deficiencies, thereby posing a risk of uncontrolled release and subsequent ecological damage. Achieving coherence among these policies has the potential to establish a standardized approach to safe deployment, however, one must acknowledge the ongoing political and economic obstacles.

In addition, the cost of production is a major barrier to widespread adoption. Smallholder farmers, common in developing regions, often lack access to expensive technologies needed for production. Around 80% rely on manure without remediation (Muhammad et al., 2020). Scaling requires reducing costs, such as optimizing bioreactor yields (10¹⁰ CFU/mL) or using local isolates, but infrastructure gaps remain. Soil variability makes scaling even more challenging. For example, sadA-expressing Pseudomonas degraded SMX 70% faster in acidic loams (pH 5.5, 5% organic matter) than in neutral clays (pH 7, 10% organic matter) due to sorption issues (Rodríguez-López et al., 2024). Also, in another study, field trials across ten sites showed consortia efficacy ranging from 20 to 80% in ARG reduction, linked to specific microbial interactions in the soil (Wang S. et al., 2024). Hence, tailoring strains to local conditions through omics-guided selection could enhance results, but this requires extensive regional data and adaptive formulations, which are expensive.

Finally, addressing these challenges needs integrated strategies. These strategies can transform lab research into practical applications, but coordinated efforts across microbiology, policy, and agriculture are crucial.

This review has comprehensively examined the challenges of antibiotic contamination in agricultural soils and the promising potential of beneficial bacteria in bioremediation. By detailing the complex sources of antibiotic pollution, the influence of soil parameters on antibiotic bioavailability, and the mechanisms by which microbial consortia can degrade antibiotics (e.g., enzymatic biodegradation, biofilm formation, and cooperative metabolism), the manuscript demonstrates how integrating molecular insights with practical remediation strategies can address both ecological and public health concerns. The discussion underscores that despite the encouraging laboratory-scale findings, challenges such as scalability, cost-effectiveness, and potential environmental risks associated with deploying engineered microbes persist.

The symbiotic association between plants, soil, and beneficial microbes has been shown to play a pivotal role in bioremediation and plant health improvement. However, a lot of information is still missing to make more positive developments from these interactions. A good bioremediation strategy involves a well-designed and targeted approach involving various approaches to achieve sustainable bioremediation (Figure 4). For full acceptance of beneficial microbes in bioremediation and sustainable agriculture, more insight is needed into the comprehensive tripartite interactions between plants, microbes, and their environment. Knowledge of microbial functions for bioremediation purposes is also very critical. Identification of candidate genes involved in antibiotics degradation and their characterization are necessary to allow for possible manipulation and editing of these genes for improved bioremediation potential and plant health promotion. Several regulatory mechanisms should also be looked into regarding genetically modified organisms for the safety of potential bioremediation potentials in the environment, since they will be deployed in the field to ascertain their potential fully.

At the center is the core objective of sustainable antibiotic bioremediation. Surrounding this are key components: (1) Optimized Microbial Consortia—featuring multi-functional degrader bacteria engineered for complementary metabolic capabilities, (2) Plant-Microbe Partnership Systems—emphasizing rhizosphere engineering to enhance plant-microbial synergies in the root zone, (3) Bioavailability Optimization Strategies—focusing on soil amendment design that considers pH, clay content, organic matter, and moisture effects, (4) Monitoring and Assessment—employing metagenomic surveillance to track antibiotic resistance genes and remediation progress, (5) Genetic Engineering Tools—utilizing CRISPR-based systems for enhanced degradation capabilities, and (6) Regulatory and Policy Framework—implementing a One Health approach aligned with Sustainable Development Goals 2 (Zero Hunger), 3 (Good Health and Well-being), and 15 (Life on Land).

Looking forward, future research should prioritize a few key areas. First, experimental approaches must be refined to quantify better how specific soil properties (pH, organic matter, texture) modulate antibiotic persistence and degradation rates, leveraging advanced metagenomic and metabolomic tools. Second, further characterization and optimization of microbial consortia, potentially through synthetic biology and gene editing, will be crucial in enhancing bioremediation efficacy while ensuring biosafety. Third, extensive field trials under diverse agricultural conditions are needed to validate laboratory findings and to tailor remediation strategies to local contexts. Finally, harmonizing regulatory frameworks internationally, supported by comprehensive risk assessments and stakeholder engagement, is essential to safely advance the application of natural and engineered microbial remediation methods (Figure 4). These integrated strategies can significantly contribute to sustainable agriculture and environmental protection under a One Health framework by bridging molecular-level research with policy and field implementation.

To chart a path forward, we propose key unanswered questions that can bridge laboratory insights and field realities. These targeted research priorities will help focus efforts on linking soil properties, microbial dynamics, and stakeholder needs for effective, scalable bioremediation.