Aquaculture is a rapidly growing global industry. According to the Food and Agriculture Organization (FAO) of the United Nations, aquaculture accounts for more than 50% of global aquatic animal production for human consumption, underscoring its growing importance in global food systems (FAO, 2024b). It is considered an essential sector for attaining the United Nations Sustainable Development Goals, particularly in the quest to eliminate hunger and promote sustainable agriculture (Wong et al., 2024). Despite several challenges, production in the sector has steadily grown, outpacing that of traditional fisheries (Kelling et al., 2023). Studies have shown that this growth is essential for providing a stable and healthy food supply and for improving the livelihoods and economic development of many regions (Wong et al., 2024).

To increase yield and meet the increasing consumer demand for fish protein, aquaculture production has shifted towards a more intensive production system that requires more technological approaches, thereby causing increased stress on fish farming and the environment (Amenyogbe, 2023). One of the key issues is the increased vulnerability of fish to health problems in intensive environments. The intensive farming practices create a habitat where pathogens can easily multiply and spread, leading to significant economic damage and sustainability issues (Elgendy et al., 2024). Estimates from the FAO Fisheries Department show that the number of infected animals is approximately 10% of all cultured aquatic animals worldwide, representing a loss of more than 10 billion USD every year (Subasinghe et al., 2023). Earlier reports from the FAO estimated disease outbreaks in the aquaculture industry to be US$9 billion per year (Kumar et al., 2021).

Advances in biotechnology have offered solutions to the numerous challenges faced by the aquaculture industry. Biotechnology provides a robust set of tools and approaches for further development of fish health management and disease prevention in aquaculture, thus overcoming the acute challenges of intensified production systems (Elgendy et al., 2024). Probiotics, which are beneficial microorganisms, are a key category of biotechnological interventions, particularly because they are widely deployed at the farm level and are increasingly positioned as antibiotic-sparing tools that support host health and water quality management in aquaculture systems (Fachri et al., 2024; Andriani, 2025). They are known to actively regulate the host microbial community and optimize the gastrointestinal health and overall physiological functions in fish (Mahato et al., 2023). Other biotechnological strategies for aquaculture disease management include vaccines, phage therapy, molecular diagnostics, and genetic selection (Priya and Kappalli, 2022; Elgendy et al., 2024; Amillano-Cisneros et al., 2025). Similarly, probiogenomics has helped to understand probiotic–host interactions at the molecular level, thus enabling the creation of more specific and compelling probiotic strains (Fachri et al., 2024). Another important biotechnological innovation is vaccines, which play a central role in disease prevention and in reducing antibiotic use in aquaculture systems (Figueroa et al., 2020; Alfatat et al., 2025).

Genetic selection programs and selective breeding are other practical long-term approaches to increase disease resistance and the general survival of fish and other aquatic organisms, particularly crustaceans, such as Pacific white shrimp (Ren et al., 2022). This approach helps create substantial populations with enhanced resistance to specific pathogens, rather than an inherently low vulnerability to pathogen threats, by systematically identifying and propagating individuals with desirable genetic traits that make them resistant to diseases (Karami et al., 2020). Recent studies have demonstrated that selective breeding can achieve substantial genetic gains in disease resistance; however, these gains are typically pathogen-specific and influenced by environmental and production conditions rather than conferring broad or universal immunity (Robinson et al., 2023; Nguyen, 2024). In addition to these proven techniques, numerous alternative treatments and new biotechnologies are being discovered to further reduce the use of antibiotics, therapeutics, and other chemicals. These include the use of phytobiotics-plant-based antimicrobials (Abdul Kari et al., 2022); nanotherapeutics to deliver drugs and clean the environment (Sabo-Attwood et al., 2021); and stem cell technology to genetically breed disease-resistant strains of fish, which is currently at a largely experimental stage and has not yet been widely implemented at the commercial aquaculture scale (Ryu et al., 2022; Robinson et al., 2023).

Although biotechnology offers significant solutions to the aquaculture industry, there are some serious environmental and human health concerns associated with its use. These issues are primarily associated with the emergence and spread of antimicrobial resistance, genetic pollution of the wild, and the potential for human infection further down the food chain (Ruben et al., 2025). This study aims to comprehensively examine global biotechnological advancements and interventions in aquaculture management, with a specific focus on their crucial role in promoting sustainable and eco-friendly aquaculture production. We also discussed the current state of progress, benefits, and inherent risks (particularly environmental and human health risks) associated with the application of biotechnology in aquaculture. Furthermore, the regulatory and ethical frameworks, effective risk-mitigation strategies for responsible use, and the formulation of relevant policy recommendations are required.

Diseases are a major constraint affecting aquaculture globally and reducing food security (Subasinghe et al., 2023). Most disease-causing pathogens are categorized into parasitic, bacterial, fungal/mixed infections, and viruses (Figure 1). They are found in all types of fish culture systems, including marine water, freshwater, brackish water, and ornamental fish (Senthamarai et al., 2023). Some common fish disease in aquaculture, the representative pathogen, clinical manifestation, and treatment is presented below in Table 1. The effects of these pathogens are often exacerbated by high stocking densities, poor water quality, and other environmental stressors, which compromise immune function, primarily through chronic activation of the stress response (e.g., hypothalamic–pituitary–interrenal axis stimulation), elevated cortisol levels, disruption of mucosal barriers (skin, gill, and gut), altered gut microbiota, and suppression of innate and adaptive immune responses, thereby increasing their susceptibility to disease outbreaks and mortality (Dai et al., 2023; Wright et al., 2023). The impacts of disease outbreaks are beyond biological, as they also result in significant economic losses, disrupt supply chains, and threaten food security (Maezono et al., 2025). As a result, there is an urgent need for modern fish health management to emphasize integrated and preventive strategies that leverage technology to address the current fish health challenges in aquaculture.

Aquaculture is constantly changing owing to consistent biotechnological applications that offer advanced disease control, productivity, and environmental sustainability. These applications, including probiotics, vaccines, antibiotic alternatives, and genetic selection, are indispensable for meeting the increasing demand for aquatic food products and simultaneously limiting their environmental impact (Figure 2). The benefits, limitations, and evidence strength of each biotechnology, and contributions towards sustainability are summarized in Table 2.

Probiotics are live microorganisms that, when administered in adequate amounts, confer health benefits to the host (Hoseinifar et al., 2024). In aquaculture, various bacterial species are employed as probiotics to enhance fish health. These microorganisms inhibit the proliferation of pathogenic bacteria through competition for nutrients, iron, and attachment sites, as well as by producing antimicrobial compounds such as bacteriocins (Li et al., 2019; Pereira et al., 2022). Beyond pathogen suppression, probiotics have been shown to improve growth performance, enhance digestive enzyme activity, promote favorable gut morphology, and strengthen the immune system, thereby increasing resistance to diseases (Soltani et al., 2019; Van Doan, 2021; Ghosh et al., 2023).

The effects of several probiotics on the immune response, growth, and disease resistance in fish have been investigated. For example, B. bifium, when used for 98 days at 10⁷ cells/100 g diet, has been observed to increase the growth performance and resistance of Nile tilapia (Oreochromis niloticus) against Aeromonas hydrophila (Ayyat et al., 2014). In a similar study on Nile tilapia, B. bifidum, Enterococcus faecium, lactobacilli sp., and Pediococcus acidilactici used at 10⁹ CFU g⁻¹ for 90 days significantly improved muscle growth, gene expression and number of intestinal villi (Silva et al., 2021). In common carp, B. bifidum, B. breve, B. lactis and different species of lactic acid bacteria at 3.2 × 10⁹ CFU/g also resulted in growth performance and improvement in hematological profile (Dima et al., 2022). Additionally, probiotics such as Acinetobacter sp., Aeromonas sp., Alcaligenes sp., Enterobacter sp., Phaeobacter sp., Pseudomonas sp have been found effective in improving growth performance, antimicrobial/antibacterial activities against pathogens, upregulated growth-related gene expression, innate, and adaptive immunity in fish species (Ramírez et al., 2020; Jinendiran et al., 2021; Makridis et al., 2021).

However, recent studies have shown that these effects are highly strain-specific and strongly influenced by host species, dosage, administration method, and environmental conditions, leading to variable and sometimes inconsistent field outcomes (Fachri et al., 2024; Ntakirutimana et al., 2025). Probiogenomics has been helpful in discovering probiotic strains that are specifically designed to meet different culture conditions in fish farming (Fachri et al., 2024). Utilizing these strains over long periods significantly reduces the vulnerability of fish and other economically important aquatic species to diseases (Hasan and Banerjee, 2020). Still, large-scale applications remain constrained by limited standardization of dosing, formulation, storage, and shelf-life assessment, which reduces reproducibility under commercial conditions (Todorov et al., 2024; Mariom et al., 2026). Additionally, biosafety concerns have been raised regarding the potential horizontal transfer of antibiotic resistance genes and the need to ensure that probiotic strains do not carry resistance or virulence factors (Calcagnile et al., 2024; Fachri et al., 2024). In shrimp culture, the incorporation of biofloc technology, which includes the addition of probiotic organisms, is effective in offering protective measures against pathogenic risks and enhancing water quality and survival rates (Kumar et al., 2021). Recent research shows that biofloc system efficiency is primarily driven by interactions among diverse microbial communities and nutrient cycling processes, rather than the effects of probiotics alone. However, practical application may be constrained by operational complexity and increased production costs (Okon et al., 2025).

The use of vaccines for disease management in aquaculture is constantly increasing. Fish vaccines can be protein, live-attenuated vaccines, virus-like particles, bacterines, and DNA vaccines. Some developments include feed-based polyvalent vaccines that protect against bacterial diseases, including vibriosis and streptococcosis, in Asian sea bass (Mohamad et al., 2021). Studies have shown the effectiveness of some commercially available vaccines in the treatment of diseases in fish species. When administered either orally, intramuscular, intraperitoneal, through dip, immersion or injection, vaccines such as IHNV plasmid vaccine, inactivated bacterial vaccine, inactivated viral vaccine, DNA plasmid, inactivated bacterial culture were found to be effective in the treatment of diseases such as Infectious hematopoietic necrosis, Enteric red mouth disease, yersiniosis, Streptococcosis, Koi herpes virus disease, Viral nervous necrosis, Aeromonas veronii infection, Vibriosis, Epizootic hematopoietic necrosis, Infectious pancreatic necrosis, Lactococcosis, Enteric septicemia disease, and motile aeromonad septicemia in fish species such as Salmon, Tilapia, seabass, koi carp, rainbow trout, Pangasius, Gray mullet, and Nile tilapia (Dhar et al., 2014; Leiva-Rebollo et al., 2024). Oral vaccination has been considered a stress-free and labor-efficient delivery approach that can reduce operational costs associated with fish handling, downstream processing, antigen purification, and cold-chain transportation (Brooker et al., 2018). However, the large-scale implementation and overall effectiveness of vaccines can be influenced by economic feasibility, labor demands, farmer adoption rates, and the consistency of vaccine performance across different aquaculture production systems (Desbois and Monaghan, 2023; Imtiaz et al., 2024).

While current vaccines are successful, there are still issues with the stability and delivery of these vaccines, particularly for oral and immersion vaccines, where antigen degradation, dosing uncertainty, and oral tolerance can limit immune stimulation (Rathor and Swain, 2024; Tammas et al., 2024). A study by Figueroa et al. (2020) showed that host genetic variation can affect the efficacy of commercial vaccines, especially against pathogens in species such as Atlantic salmon (Piscirickettsia salmonis). In addition to host genetics, vaccine performance is further influenced by the administration route, antigen dose, environmental conditions (e.g., temperature and salinity), handling stress, and pathogen strain diversity, leading to variable protection under field conditions (Ben Hamed et al., 2021; Wangkahart et al., 2023; Imtiaz et al., 2024).

In addition, welfare and biosafety considerations remain relevant, as injectable and live-attenuated vaccines have been associated with adverse reactions, handling stress, and, in some cases, risks related to reversion to virulence or transmission to nontarget species (Tripathi and Dhamotharan, 2022). To overcome these challenges, new technologies like Omics based”, nano-carrier-based adjuvants and environmentally friendly vaccines like plant-based vaccines, which are efficient and cost-effective, require small doses, and do not require the use of antibiotics are being considered to enhance protective efficacy, including subunit and DNA vaccines (Shivam et al., 2021; Giri et al., 2021; Elgendy et al., 2024). Such innovations are necessary to support sustainable aquaculture practices and reduce reliance on antibiotics; however, they must be implemented alongside careful evaluation of efficacy, safety, and practical feasibility (Alfatat et al., 2025).

Antibiotics have been used for disease management in aquaculture for many years. However, owing to growing concerns about antimicrobial resistance and human health concerns, it has become critical to regulate the use of antibiotics in aquaculture (FAO, 2018). Antibiotics, including oxytetracycline, florfenicol, oxolinic acid, and erythromycin, are commonly administered orally to aquaculture species such as yellowtail, rainbow trout, and kuruma prawn. Withdrawal periods vary widely, ranging from 5 days (e.g., amoxicillin, florfenicol in yellowtail) up to 30 days (e.g., erythromycin in yellowtail, oxytetracycline in rainbow trout, oxolinic acid in kuruma prawn), highlighting the need to prevent drug residues and ensure food safety of aquaculture products (Okocha et al., 2018).

In a study, Manna et al. (2022) found oxytetracycline residues in Pangasianodon hypophthalmus muscle were below MRL, but elevated in liver and kidney, and suggested a 4-day withdrawal at 28 ± 1.5°C. In a similar study on GIFT tilapia, Wang et al. (2025) reported that while residual Sulfamethoxazole reached safe levels within three days, skin and other tissues retained the antibiotic longer. As such, the study recommended a minimum withdrawal period of 11 days before harvest to ensure consumer safety. Lulijwa et al. (2020) reported the use of 67 antibiotic compounds across 11 of 15 countries surveyed between 2008 and 2018. Oxytetracycline, sulphadiazine, and florfenicol were used in 73% of these countries. On average, each country applied 15 antibiotics, with Vietnam (39), China (33), and Bangladesh (21) recording the highest numbers. The authors also presented strong evidence linking antibiotic use to food safety risks, occupational exposure, and the development of antimicrobial resistance.

Nevertheless, recent evidence indicates that antibiotic use remains substantial and uneven across regions, driven by differences in regulatory enforcement, availability of usage data, and monitoring capacity, particularly in low- and middle-income aquaculture producing countries (Ferri et al., 2022; Hossain et al., 2022; Ljubojević et al., 2024). Outcomes associated with antibiotic use also show high variability and are influenced by species-specific sensitivity, environmental and seasonal factors, feed practices, and differences in antimicrobial application and restriction regimes (Limbu et al., 2021; Thiang et al., 2021; Raza et al., 2022). Additionally, the use of antibiotics in aquaculture contributes to selective pressure that promotes the emergence and environmental dissemination of antibiotic-resistant bacteria and resistance genes, with documented risks to aquatic ecosystems, food safety, and public health (Hossain et al., 2022; Goh et al., 2024; Milijašević et al., 2024). These challenges are compounded by limitations in current surveillance and detection methods that often fail to capture resistance genes or provide comparable results across studies and regions (Farías et al., 2024; Milijašević et al., 2024).

In terms of regulation, several major aquaculture-producing countries show wide variation in antibiotic governance. In some countries, such as China, Thailand, and Vietnam, legislation that singles out chemicals that can be used in aquaculture has been adopted, including rules on how these chemicals must be used (FAO, 2013). Bangladesh and Egypt lack national aquaculture-specific antibiotic policies, while Russia provides only general therapeutic lists for animal husbandry. In India, certain antibiotics are banned for use in shrimp farming, but no official list of approved compounds exists (CAA, 2022). In contrast, Australia and the UK allow veterinarians to prescribe antibiotics outside authorized lists, with Australia relying on case-by-case approvals (APVMA, 2014; VMD, 2024). Notably, Norway and the Faroe Islands have minimal antimicrobial use, exceeding regulatory expectations (NORM, 2024; MFNR, 2020). In major importing markets such as the EU, the United States, and Japan, the enforcement of strict antibiotic residue standards has resulted in frequent border rejections and destruction of between 20-28% of non-compliant products. FAO data show that antibiotic residues are a leading cause of aquaculture import rejections, particularly from Southeast and East Asia (Geetha et al., 2020; FAO, 2024a).

While antibiotic misuse, weak regulation and enforcement remain common in low and middle-income countries and regions dominated by small-scale farms (Schar et al., 2018), establishing a globally harmonized standard that strengthens enforcement and monitoring capacity could reduce antibiotic resistance risks while improving trade transparency and export revenues. In addition, promoting alternatives such as vaccines, probiotics, bacteriophages, and plant-based therapies is critical to reducing antimicrobial resistance risks (Schar et al., 2018; Bondad-Reantaso et al., 2023) and ensuring that NGOs and certification bodies support antibiotic stewardship through WHO-guided awareness and incentive programs.

An environmentally sustainable approach involves the use of phytobiotics or plant-derived compounds with antimicrobial properties that have been shown to boost immune responses in aquatic organisms (Abdul Kari et al., 2022). A similar approach is phage therapy, which involves the use of bacteriophages to target and eliminate bacterial pathogens (Elgendy et al., 2024). In addition, nanotechnology, which consists of the use of nanoparticles to deliver drugs and antimicrobial agents, provides a new approach for managing diseases in aquaculture without causing significant effects on the environment (Sabo-Attwood et al., 2021). The development of new immunostimulants, prebiotics, and synbiotics could also help strengthen the immunity of aquatic organisms, thereby lessening their dependence on antibiotics (Elgendy et al., 2024).

Genetic selection is a key strategy to improve disease resistance and productivity in aquaculture through cumulative and heritable gains. Modern breeding programs use quantitative genetics and selective breeding approaches to enhance beneficial traits such as growth performance and resistance to infectious diseases (Sciuto et al., 2022). Selective breeding has been successfully applied in shrimp, where improvement programs for Penaeus vannamei have increased resistance to major pathogens and improved survival (Ren et al., 2022), and in salmonids, where resistance-associated loci have supported more targeted selection strategies (Karami et al., 2020). However, the outcomes of genetic selection for disease resistance are highly species- and pathogen-dependent, as resistance traits are typically polygenic and involve many genes with minor additive effects, which increases the complexity and variability of breeding outcomes (Robinson et al., 2023). Trade-offs may also arise, as selection for disease resistance can be associated with unintended effects on growth, tolerance, or pathogen transmission if not carefully managed (Robinson et al., 2023). In addition, genetic gains may be reduced by genotype-by-environment interactions, where resistance expressed in nuclear breeding populations does not fully translate to commercial farming conditions (Kang et al., 2025).

Genetic selection also faces both practical and ecological constraints. Disease challenge testing required to identify resistant individuals is often costly and time-consuming, limiting the scale and accessibility of breeding programs, particularly for small- and medium-scale producers (Nguyen, 2024). Long-term sustainability may also be affected by reductions in within-population genetic diversity if the selection intensity is high, which can compromise resilience over time (Kang et al., 2025). Furthermore, ecological risks, such as genetic introgression from farmed escapees, have been reported. According to a study by Besnier et al. (2011), escapees from fish farms can compromise the genetic integrity of wild Atlantic salmon populations, with gene flow from multiple farmed strains significantly reducing the detectable genetic change using neutral markers. Simulations based on nine microsatellite loci showed that when multiple farm strains contributed to introgression, standard analyses underestimated admixture, highlighting the ecological risk of hidden genetic homogenization in wild populations (Besnier et al., 2011). In another study, analysis of scale samples from over 6,900 wild Atlantic salmon across 105 rivers showed that genetic introgression from farmed escapees alters the natural life-history traits by increasing growth rates, accelerating migration age and sexual maturity, with effects varying significantly among populations These findings highlight the ecological impact of genetic selection in aquaculture, demonstrating how farmed genetic inputs can reshape growth dynamics and potentially influence population structure and resilience in the wild (Bolstad et al., 2021). Therefore, the need for robust risk assessment when managing farmed and non-native genetic resources remain important consideration for maintaining environmental integrity (Sonesson et al., 2023).

Despite the benefits of biotechnology in aquaculture, its widespread use presents several serious risks that should be carefully considered to ensure the sustainability of this important sector. Major issues include the development of antimicrobial resistance (AMR), genetic pollution of wild populations, environmental impact, and ethical concerns (Figure 3). For example, the widespread use of antibiotics in aquaculture imposes selective pressure that favors the growth of antibiotic-resistant bacteria (Milijasevic et al., 2024). The subsequent entry of these resistant microbes and their associated genes into aquatic environments through aquaculture wastewater and farm effluents creates AMR reservoirs, which represent a significant environmental and public health hazard. Similarly, aquaculture systems integrated into terrestrial habitats and human settlements have facilitated the spread of resistant bacteria across aquatic–terrestrial interfaces. Importantly, these AMR risks are largely attributable to the antibiotic use itself, whereas other biotechnological tools, such as probiotics, immunostimulants, phage therapy, and antimicrobial peptides, are primarily positioned as mitigation strategies aimed at reducing antibiotic dependence rather than as direct drivers of resistance (Bondad‐Reantaso et al., 2023).

Antibiotic residues can persist in aquaculture water and sediments after treatment, contributing to the emergence and spread of AMR. These residues could enter aquatic environments through runoff, leaching, and effluent discharge, promoting the selection of resistant bacteria and resistance genes (Vilca et al., 2021). Prolonged exposure to antibiotic residues could alter microbial community composition and diversity, disrupt ecological stability and favor opportunistic pathogens over beneficial microorganisms (Chen et al., 2020a). Although vaccination is widely adopted, its effectiveness remains limited in early aquatic life stages and in species with underdeveloped adaptive immune systems (Kumar et al., 2023; Robinson et al., 2023).

Bacteriophages have shown strong effectiveness against major aquaculture pathogens, including Aeromonas, Vibrio, Pseudomonas, and Flavobacterium, offering eco-friendly, host-specific control of biofilm-forming and multidrug-resistant bacteria. However, bacterial resistance mechanisms require infection-specific phage selection and genetic optimization to improve long-term therapeutic performance (Lim et al., 2025). Recent studies show strain-specific probiotic efficacy, with Bacillus and Streptomyces outperforming Lactobacillus in pathogen suppression due to spore resilience and bioactive metabolite production (Giri et al., 2024; Hoseinifar et al., 2024). However, performance varies with host genotype, dosage, and gastrointestinal survivability. Optimized dosing significantly improves growth and survival outcomes, highlighting the need for species-specific probiotic validation (Tayyab et al., 2025).

Another essential issue is genetic contamination, where farmed fish escaping aquaculture systems can alter the genetic structure of wild stocks, impairing their genetic diversity and long-term viability (Toledo-Guedes et al., 2024). Several studies have established that Atlantic salmon from domesticated facilities pose a major threat to native fish populations through genetic introgression in regions such as North America and Northern Europe (Glover et al., 2020; Kolavani and Mather, 2024). Furthermore, the establishment of non-native farmed taxa can initiate resource competition, predation of native organisms, and introduction of novel pathogens into recipient ecosystems (Zehra et al., 2025). Newer genetic technologies, including CRISPR/Cas9, also face technical and ethical challenges such as off-target mutagenesis and biosafety concerns associated with the release or escape of genetically modified organisms into natural ecosystems (Puthumana et al., 2024). Consequently, genetic interventions in aquaculture continue to face obstacles to wider acceptance owing to their potential ecological, environmental, and animal welfare implications, as well as precautionary regulatory approaches in many regions (Amillano-Cisneros et al., 2025).

Although alternative therapeutic options used in aquaculture, such as probiotic formulations, phytogenic additives, and other feed-based interventions, are often promoted as environmentally sustainable solutions, they also present their own set of risks, including inconsistent efficacy, toxicity concerns, high production costs, and environmental persistence (Elgendy et al., 2024). In addition, the sustainability of plant-based additives has rarely been assessed beyond their antimicrobial or immunostimulatory effects, with limited consideration of life-cycle impacts, sourcing pressure on medicinal plants, land-use trade-offs, or scalability across production systems (Okon et al., 2025). Across biotechnology applications, regulatory challenges are frequently linked not only to the absence of legislation but also to enforcement gaps, limited standardization, and substantial international inconsistency in governance frameworks (Luthman et al., 2024; Milijašević et al., 2024). To ensure the long-term sustainability of these interventions, standardized testing protocols, clearer operational specifications, and context-specific regulatory oversight are essential to address the environmental, health, and ethical risks associated with aquaculture biotechnology (Amillano-Cisneros et al., 2025).

Some chemicals used in aquaculture are valuable for increasing productivity and controlling the spread of infectious parasites and diseases. Pesticides containing organophosphate compounds have also been used to control pests in ponds. However, these compounds could become toxic to fish and other aquatic animals, especially if used at relatively high concentrations and often lead to environmental impacts, particularly aquatic pollution (Mavraganis et al., 2020). Figure 3 depicts some of these environmental impacts. Additionally, the incorporation of therapeutics and growth enhancers in aquaculture feed increases chemical inputs into aquaculture wastewater. Discharge of untreated aquaculture wastewater and effluents into aquatic ecosystems can contribute to nutrient enrichment, contamination, bioaccumulation of toxic substances, disease proliferation, and ecological degradation, potentially reducing biodiversity and threatening the sustainability of economically important aquatic resources (Ojewole et al., 2024).

When biological intervention in aquaculture is not properly managed, impacts such as the degradation of water quality can be a consequence. For instance, oil-adjuvanted fish vaccines have been associated with reduced feeding efficiency and increased metabolic waste production, contributing to elevated dissolved inorganic nitrogen and particulate organic matter in intensive systems. Field observations in salmonid farms have reported localized sediment enrichment beneath cages, with total organic carbon (TOC) concentrations exceeding background levels by two to fourfold following repeated vaccination and high-biomass production cycles (Bohnes et al., 2019). Additionally, probiotic misuse or over-application can increase biological oxygen demand (BOD) and microbial respiration, with experimental pond and recirculating aquaculture system (RAS) studies documenting reductions in dissolved oxygen of 15-30% and transient increases in ammonia-nitrogen (NH₃-N) concentrations above 0.2 mg/L thresholds known to impair fish health and exacerbate eutrophication risk in receiving waters (Tarnecki et al., 2017; Ringø et al., 2020). Moreover, the release of live microbial strains through aquaculture effluents has been linked to altered microbial community structure and the proliferation of antimicrobial resistance genes, with metagenomic surveys detecting up to 10-fold higher relative abundance of resistance determinants in sediments adjacent to aquaculture operations compared to reference sites, posing indirect human health risks via environmental reservoirs (Cabello et al., 2016; Watts et al., 2017). Genetic selection for rapid growth and elevated feed intake has also been shown to increase nitrogen and phosphorus excretion per unit biomass by 20-40% in fast-growing strains when feed formulations and feeding regimes are not optimized, intensifying nutrient loading, phytoplankton blooms, and hypoxic events in poorly flushed systems (Troell et al., 2014).

Additionally, the escape of fish from aquaculture production facilities poses a threat to fish biodiversity and the environment. This includes altering the genetics of indigenous species through inbreeding, hybridization, and selective breeding (Atalah and Sanchez-Jerez, 2020). This could lead to the loss of species diversity, compromise the structure of the wild population, reduce genetic viability over several generations, and eventually cause the extinction of some endemic species. Repeated hybridization and gene flow between farmed and wild fish species have resulted in irreversible loss of genetic diversity, reduced environmental adaptability, fitness reduction, and potential local extinction of wild fish in sub-Saharan Africa (Sanda et al., 2024).

Conversely, emerging biotechnologies offer promising ways to mitigate these environmental effects by replacing harmful practices with sustainable biological solutions. To address chemical pollution, innovative systems now utilize microalgae to naturally clean wastewater and recycle nutrients, effectively reducing the release of toxic compounds into the ecosystem (Li et al., 2021; Villar-Navarro et al., 2022). Furthermore, tools such as CRISPR-Cas9 and nutrigenomics allow for the breeding of fish that are naturally resistant to diseases, significantly lowering the need for organophosphates and antibiotics (Marchandise, 2024; Iqbal et al., 2025). However, these genetic advancements must be managed carefully to avoid worsening the threats posed by escapes. Therefore, implementing reproductive sterility in farmed stocks is viewed as a critical biosafety measure to prevent genetic mixing with wild populations (Robinson et al., 2023; Xu et al., 2023).

Considering that nearly 50% of the fish traded in international markets come from aquaculture, it is important to ensure that the aquaculture sector produces safe food (Miao and Wang, 2020). The indiscriminate use of antimicrobials in aquaculture results in the occurrence of residues in aquaculture products and the associated harmful health effects in humans. Major public health concerns that have been identified include the development of antimicrobial drug resistance, hypersensitivity reactions, carcinogenicity, mutagenicity, teratogenicity, bone marrow depression, and disruption of normal intestinal flora (Okocha et al., 2018). Some studies have projected that antimicrobial resistance could cause up to 10 million deaths and a 3.8% global economic loss by 2050 (Frei et al., 2023; Kumari et al., 2023).

Antibiotic residues, heavy metals, natural processes, and climate change have been identified as the drivers of antimicrobial resistance in the aquatic environment (Kusi et al., 2022). The presence of antibiotic residues in aquaculture products may contribute to the emergence of bacterial resistance and toxicity in consumers, potentially resulting in illness and/or mortality. For example, chloramphenicol residues elevate the risk of cancer and, even in minimal quantities, may induce aplastic anemia, a condition that halts bone marrow production of red and white blood cells and is frequently irreversible and lethal (Priya and Kappalli, 2022; Nyamagoud et al., 2025). Additional hazardous effects include immunopathological consequences and carcinogenicity associated with sulfamethazine, oxytetracycline, and furazolidone; mutagenicity and nephropathy linked to gentamicin; and allergic reactions induced by penicillin (Kyuchukova, 2020; Bacanlı, 2024; Oladeji et al., 2025).

Across regions, the adoption of aquaculture biotechnology exhibits significant divergence due to varying policy frameworks that allocate regulatory risk, economic costs, and social legitimacy in distinct ways. This disparity results in selective adoption, as highlighted by Wray-Cahen et al. (2024). The most pronounced differences arise in the regulation of genetically modified (GM) and gene-edited organisms, where contrasting policies not only influence technology approval but also shape the prioritization of certain types of innovations and the stakeholders involved in these processes.

In the European Union, a precautionary and process-based GMO regime guided by Directive 2001/18/EC and Regulation (EC) No. 1829/2003 imposes rigorous pre-market risk assessments, traceability requirements, labeling mandates, and post-market environmental monitoring (GOV.UK, 2020). While these measures are designed to ensure safety, their associated compliance costs and protracted approval timelines have stifled the commercial use of GM and genome-edited aquatic animals. As a result, the focus of innovation has shifted toward non-GM health biotechnology, vaccinations, and both conventional and genomic selection methods, leaving transgenic or genome-edited fish underutilized (Christoforou, 2012; Bruetschy, 2019; Dolezel et al., 2025). In contrast, Norway adopts strict environmental regulations while employing incentive-based licensing tools, such as green, development, and eco-technology licenses. China has strengthened its aquaculture sector through advances in production technologies, including feeding strategies and seed quality, while also enhancing aquatic product traceability, food safety standards, and routine inspection systems to improve overall product quality (Liu et al., 2018; Han et al., 2018). This approach not only fosters technological and biotechnological innovation but also illustrates how regulatory strictness can be effectively combined with incentives to establish credible governance frameworks.

A different but related zoning-based approach is observed in South Australia, where regulatory policy, specifically the Zones–Lower Eyre Peninsula Policy (2013), addresses environmental risks by designating specific aquaculture zones and permitted species. This framework facilitates gradual adoption of biotechnology by allowing the introduction of new breeds and health-management innovations without the direct engagement of genetic modification (Lauer et al., 2015). In the United States and Canada, by comparison, while the legal framework permits biotechnology adoption, it remains highly selective. Transgenic fish undergo case-by-case reviews as new animal drugs, leading to some approvals, such as the AquAdvantage salmon, albeit at substantial financial and temporal costs. This has ultimately restricted adoption to capital-intensive and high-value corporate entities (Logar and Pollock, 2005; Grossman, 2016).

In contrast, countries such as Japan, Argentina, and Brazil have adopted product-based and risk-proportional regulatory systems that exempt certain genome-edited organisms lacking foreign DNA from GMO regulations. This results in significantly fewer regulatory hurdles and faster commercialization compared to the EU and North America (Hallerman et al., 2022; Lim and Choi, 2023). China demonstrates a hybrid, state-coordinated model where strategic investments, insurance plans, and extension services work in tandem to enhance the adoption of system-level health biotechnologies (N’Souvi et al., 2025). However, strict regulations surrounding genetic resources and intellectual property influence the direction and openness of innovation.

Conversely, in Sub-Saharan Africa, the primary limitation arises not from regulatory stringency but from weak implementation of existing policies. While most countries have biosafety and aquaculture regulations, issues like insufficient institutional capacity, lack of transparency, and ineffective extension systems hinder the adoption of technologies. Technologies that could be more readily utilized, such as hormonal sex control, diagnostics, and selective breeding, remain underexplored (Rege and Ochieng, 2022). Nigeria exemplifies this situation, featuring a liberal Fisheries Act (2014) that supports the licensing of non-native and genetically enhanced strains. However, the implementation of advanced biotechnology has stalled due to inadequate enforcement and monitoring infrastructure (Sanda et al., 2024).

Collectively, these comparisons reveal that uneven global standards do not merely facilitate or restrict the development of aquaculture biotechnology; they critically influence which technologies flourish, how investment concentrates, and how risks and benefits are distributed across regions.

The application of biotechnology in aquaculture requires a cautious examination of ethical issues, including animal welfare, environmental consequences, and social justice (Ciliberti et al., 2023). It is crucial to maintain animal welfare in order to ensure food production and improve food security worldwide (Robinson et al., 2023). An inefficient welfare status in intensive aquaculture facilities may foster health issues, disease outbreaks, increased antibiotic consumption, and ecosystem decline (Gonzalez, 2023). Considerable attention should be paid to environmental issues, including genetic pollution and long-term ecological impact. Aquaculture must balance the environmental stewardship and food production imperatives. An example is the escape of farmed fish, which endangers the genetic purity of the wild fish (Alvanou et al., 2023).

In the use of probiotics, vaccines, and other alternative therapies, best practices require that they be used in specific ways to maximize their effectiveness and reduce resistance. This includes heightened antibiotic stewardship and emphasis on probiotics, prebiotics, and phytobiotics to prevent diseases (Abdul Kari et al., 2022). Surveillance of antibiotic residues and resistance genes is of utmost importance (Chen et al., 2020b). Additionally, the development of vaccines should focus on stable and cost-effective formulations with efficient delivery systems.

It is important to note that long-term sustainability of aquaculture requires the incorporation of biotechnology into sustainable systems and the implementation of holistic management systems. This shift has not only taken the form of individual interventions, but also holistic approaches that take into account various aspects of the farming industry.

Plant-based additives such as phytogenics or phytobiotics are being incorporated into aquaculture practices (Table 3). It is most commonly included in aquafeeds to improve the resilience, growth, and health of cultured aquatic organisms, while lowering reliance on synthetic chemotherapeutics and antibiotics (Hossain et al., 2024; Okon et al., 2025). Bioactive secondary metabolites, such as phenolics, flavonoids, alkaloids, terpenoids, and saponins, are found in these additives, which are derived from herbs, leaves, seeds, and essential oils. These compounds have antimicrobial, antioxidant, immunomodulatory, and digestive stimulatory effects in aquaculture species (Ahmadifar et al., 2021; Firmino et al., 2021).

Factors such as enhanced growth performance and feed efficiency have been linked to plant-based dietary supplements and are attributed to increased digestive enzyme activity and improved gut morphology, especially in omnivorous species, such as Nile tilapia (Oreochromis niloticus) and channel catfish (Ictalurus punctatus) (Reverter et al., 2014; Dawood et al., 2018). For instance, oregano, thyme, and garlic essential oils exhibit significant antimicrobial and appetite-stimulating properties, enhancing the feed conversion efficiency and survival rates in intensive culture settings (Khalafalaa et al., 2025).

Among plant-based additives, Moringa oleifera has become a prominent subject of research in aquaculture because of its high protein content, balanced amino acid profile, and rich presence of bioactive compounds, such as quercetin, chlorogenic acid, and glucosinolates (Saleh et al., 2025). The incorporation of M. oleifera either as a leaf meal or extract in fish diets has been shown to improve growth, hematological parameters, antioxidant enzyme activity, and innate immune responses in Nile tilapia and African catfish (Clarias gariepinus), while also enhancing resistance to bacterial pathogens such as Aeromonas hydrophila (Nassar et al., 2024).

Additionally, plant-based additives play a crucial role in reducing oxidative stress by increasing endogenous antioxidant defense mechanisms such as superoxide dismutase, catalase, and glutathione peroxidase. This enhancement leads to improved physiological stability during handling, storage, and exposure to environmental stresses (Ahmadifar et al., 2021). Genetic studies have suggested that phytogenic compounds can regulate genes related to immunity, metabolism, and stress tolerance, underscoring their multifunctional role in host physiology (Firmino et al., 2021).

Although these advantages exist, the effectiveness of plant-based additives is greatly affected by dosage, formulation, and species-specific reactions, as high inclusion levels may result in diminished palatability or anti-nutritional consequences (Reverter et al., 2014). Variability in plant chemotypes, agronomic conditions, and extraction methods complicate standardization and reproducibility across studies (Firmino et al., 2021). These challenges highlight the necessity for controlled formulation strategies, including microencapsulation and thorough dose optimization trials before commercial implementation.

Life cycle assessment (LCA) studies suggest that phytogenic feed additives can lower the environmental footprint of aquaculture by improving feed conversion efficiency, reducing disease-related losses, and decreasing emissions associated with pharmaceutical production and therapeutic treatments (Bohnes et al., 2019).

Sourcing pressure on medicinal and aromatic plants presents a growing sustainability concern, as increased demand for phytogenic compounds may intensify overharvesting of wild plant populations, threaten biodiversity, and disrupt local ecosystems if not managed responsibly (Firmino et al., 2021). Cultivation-based sourcing, agro-ecological production systems, and the use of agricultural by-products or residual biomass have therefore been recommended as strategies to mitigate ecological pressure while ensuring consistent quality and supply (Dawood et al., 2018; Firmino et al., 2021).

Land-use trade-offs further complicate the sustainability profile of plant-based additives, particularly when feed additive crops compete with food crops for arable land, water, and other resources. Expanding the cultivation of phytogenic plants without integrated land-use planning may contribute to deforestation, habitat conversion, or indirect land-use change, diminishing net environmental gains (Bohnes et al., 2019). Conversely, species such as Moringa oleifera, which can be cultivated on marginal lands with relatively low input requirements, present a more favorable sustainability profile and align with circular bioeconomy principles when integrated into multifunctional agro-aquaculture systems (Saleh et al., 2025).

The future use of plant-based additives in aquaculture relies on mechanistic validation using systems biology tools, extensive field evaluations in commercial farming settings, and standardized regulatory frameworks that guarantee safety, efficacy, and environmental compatibility. Strategically developed and regulated phytogenic additives, such as Moringa oleifera, offer a promising approach for enhancing sustainability and health in aquaculture production systems (Firmino et al., 2021).

In line with the goal of increasing productivity and disease resistance, biotechnology applications should focus on innovations that support environmental sustainability and promote human health (Macwan et al., 2025). Biotechnological research should focus on disease prevention, sustainable feeds, and genetic improvement programs to develop strong aquatic populations (Dunham, 2023; Zhu et al., 2024). Policies should focus on capacity building to help farmers make these improvements, especially in developing countries, where aquaculture plays a key role in food security (Henriksson et al., 2021). In addition, with the current advancements in Artificial Intelligence (AI), policies should encourage the use of precision aquaculture, in which biotechnology innovations and artificial intelligence are used to maximize fish health and efficiency (Lal et al., 2024).

Policies to promote ecosystem and environmental integrity in aquaculture, particularly in biotechnology, must be holistic. The main priority should be to improve environmental governance in the context of aquaculture water quality and biodiversity conservation (Shamoun-Baranes et al., 2021). This will require the development of rules on waste disposal in aquaculture plants, water resource charges, and clean production assessment. Policies that promote the use of effective technologies for treating aquaculture wastewater containing residues and contaminants should be promoted (Tom et al., 2021; Das et al., 2024). It would be beneficial to develop a national framework to evaluate the environmental impacts using policy-based scenarios (Bohnes et al., 2021). These policies need to ensure strict containment to reduce genetic contamination and promote the generation of sterile fish by editing the genes (Robinson et al., 2023). New aquaculture projects and biotechnological applications should be subjected to environmental impact assessments, which should include an analysis of their impact on native species, pathogens, and genetic diversity. To ensure sustainable aquaculture, there is a need for international cooperation to harmonize regulations, share knowledge of best practices, and promote solutions that support the environment and meet global fish demands (Alleway et al., 2023).

Biotechnology is an important aspect that makes aquaculture a viable and sustainable sector. It provides a significant benefit in improving fish health by using probiotics, advanced vaccines, and genetic selection, thus reducing the occurrence of diseases, dependence on antibiotics, and overall operational efficiency. These innovations have a positive impact on food security and environmental stewardship. Nevertheless, numerous issues and challenges are associated with these tools and innovations. These challenges include increased antimicrobial resistance, the risk of genetic contamination of wild fish populations, and several environmental, human health, and ecological effects. However, these issues must be addressed carefully and in a controlled manner. Further biotechnological studies should focus on the development of environmentally friendly alternatives and sustainable technologies suitable for aquaculture production and growth. This should also be supported by sound and dynamic regulatory frameworks, holistic monitoring programs, and combined management strategies that offer high ethical standards and environmental protection.