Antibiotic residues (ARs) in foods of animal origin pose a multifaceted challenge at the intersection of public health, food technology, and veterinary practice, raising concerns ranging from consumer safety to the sustainability of traditional food systems [1, 2]. In livestock production, antibiotics are widely administered for therapeutic, prophylactic, and growth-promoting purposes; however, their misuse and overuse often result in residual compounds persisting in milk, meat, and fish [3–5]. When inadequately controlled, these residues enter the food chain, creating risks for both consumers and food systems [1, 2, 6–10].

Numerous studies have reported high prevalence rates of AR contamination, with certain regions exhibiting particularly elevated levels due to weak regulatory enforcement and inadequate compliance with withdrawal periods [2, 11]. Although the public health implications of ARs, particularly their contribution to antimicrobial resistance (AMR), are well established, their effects on food-processing technologies remain comparatively underexplored. A key technological concern is the interference of ARs with microbial fermentation, a process central to the production of many foods [12, 13]. Fermentation relies on microbial metabolism to enhance sensory, nutritional, and safety attributes [14–18]. Even at low concentrations, antibiotics can inhibit or eliminate beneficial microorganisms, resulting in fermentation failures, quality defects, and economic losses [12, 14, 19, 20]. This risk is particularly evident in dairy products such as cheese and yogurt, fermented meat products such as salami, and traditional fish products such as fish sauce [13, 21].

Mechanistically, different antibiotic classes disrupt microbial pathways involved in cell wall synthesis and protein translation, directly impairing lactic acid bacteria (LAB), yeasts, and halophilic microbiota. These disruptions can lead to delayed acidification, impaired enzymatic activity, and fermentation failure, ultimately compromising product quality, safety, and shelf life [6, 12].

Beyond technological disruption, ARs carry important public health implications. Chronic dietary exposure to low levels of antibiotics contributes to the emergence and dissemination of AMR, which is now recognized as a global health crisis [1, 15, 22, 23]. AMR undermines the effectiveness of antibiotics in both human and veterinary medicine [24, 25]. In addition, ARs can trigger hypersensitivity reactions, allergic responses, and, in some cases, carcinogenic effects [26, 27].

In addition to microbial inhibition, AR interference may promote pathogen survival and biogenic amine accumulation in fermented products, further increasing food safety risks. Despite these significant technological implications, most previous studies have focused primarily on public health and regulatory aspects, with limited integration of microbiological, pharmacological, and food-processing perspectives. Furthermore, differences in susceptibility among industrial, artisanal, and traditional fermentation systems remain insufficiently characterized, representing an important area requiring further investigation.

Despite the existence of international regulatory frameworks, compliance remains challenging, particularly in resource-limited settings. Codex Alimentarius and the European Union have established maximum residue limits (MRLs), but effective enforcement depends on sensitive detection systems and producer awareness [11, 28–31]. Although advanced analytical methods such as liquid chromatography–mass spectrometry (LC-MS) and enzyme-linked immunosorbent assay (ELISA) provide high sensitivity and specificity, their cost and technical requirements limit their adoption in many low-income regions [19, 21, 32–34]. The problem also affects small-scale and traditional producers, for whom fermentation practices constitute an important component of cultural heritage [14, 15, 35, 36]. Consequently, AR contamination not only compromises product safety and quality but also threatens the preservation of traditional food-processing practices [11, 20, 37].

Addressing AR-related risks requires an integrated approach that combines scientific innovation, regulatory enforcement, and stakeholder engagement [2, 11, 29, 30, 38, 39]. Promising strategies include developing residue-tolerant starter cultures that maintain fermentation activity under low antibiotic pressure [21, 31, 37] and adopting alternative husbandry practices, such as improved hygiene and vaccination programs, to reduce antibiotic dependence [1, 4, 30]. Equally important are education and awareness programs targeting farmers, processors, and consumers to promote responsible practices and strengthen compliance [3, 11, 28, 30, 39].

Although substantial progress has been made in understanding the occurrence of ARs and their role in AMR, current knowledge regarding their technological consequences in fermentation-based food systems remains fragmented. Most available studies have focused predominantly on toxicological concerns, AMR, and regulatory issues, whereas comparatively little attention has been devoted to the mechanisms through which ARs influence fermentation performance, microbial ecology, and product quality. Furthermore, available evidence is scattered across different food matrixes, and comparative analyses among dairy, meat, and aquatic fermentation systems are limited. Existing studies rarely integrate microbiological, pharmacological, technological, and regulatory perspectives into a unified framework. In addition, differences in susceptibility among industrial, artisanal, and traditional fermentation systems have not been comprehensively evaluated. The absence of standardized thresholds for fermentation inhibition, limited information regarding the long-term effects of ARs on food microbiomes, and insufficient assessment of emerging monitoring technologies represent major knowledge gaps that hinder the development of effective mitigation strategies and harmonized regulatory approaches.

Therefore, this review aims to provide a comprehensive and integrative analysis of the technological risks associated with ARs in foods of animal origin, with particular emphasis on their disruptive effects on microbial fermentation processes. Specifically, the review examines the occurrence of ARs across different food categories and the factors contributing to their persistence, including pharmacokinetic behavior and processing stability [6]. It further analyzes the mechanisms through which different antibiotic classes interfere with fermentation processes and links these effects to measurable technological outcomes, including acidification rate, proteolysis, flavor development, and product quality. In addition, the review critically evaluates current detection and monitoring approaches, highlighting both technological advancements and practical limitations encountered in resource-limited settings. Finally, it identifies key research gaps and proposes a structured mitigation framework that integrates preventive measures, monitoring strategies, and technological interventions, thereby addressing a critical yet underexplored dimension of ARs in food systems.

A conceptual framework illustrating the pathways and technological impacts of ARs in fermentation systems is presented in Figure 1[4, 21, 30, 39].

This review was conducted using a structured narrative approach to synthesize current knowledge regarding ARs in foods of animal origin and their technological implications. Relevant literature was retrieved from major scientific databases, including PubMed, Scopus, Web of Science, and Google Scholar. The search strategy combined keywords such as “antibiotic residues,” “fermented foods,” “lactic acid bacteria,” “food safety,” “antimicrobial resistance,” and “detection methods.”

The selection criteria focused primarily on peer-reviewed articles published within the last 10 years, with particular emphasis on studies investigating the occurrence of residues, their technological effects on fermentation processes, analytical detection methods, and mitigation strategies. Seminal and highly cited earlier studies were also included, where appropriate, to provide historical background and mechanistic insights.

Studies were included if they provided quantitative or qualitative data on ARs in animal-derived foods, experimental evidence describing their effects on microbial fermentation, or information on analytical approaches for residue detection and monitoring. Articles dealing exclusively with clinical or environmental aspects without direct relevance to food systems were excluded.

Although this review followed a structured approach for literature selection and synthesis, certain limitations should be acknowledged. Variations in study design, analytical methodologies, sampling procedures, and regional surveillance capacities may affect the comparability of reported findings. In addition, differences in regulatory frameworks and residue-monitoring practices among countries may contribute to heterogeneity in the available evidence.

Therefore, the findings presented in this review should be interpreted in light of these methodological and geographical limitations. Nevertheless, the broad inclusion of studies from different regions and production systems provides a comprehensive overview of the current state of knowledge regarding the occurrence, technological impacts, detection, and mitigation of ARs in foods of animal origin.

The occurrence of ARs in foods of animal origin has emerged as a major concern for both public health and food safety. These residues primarily result from the administration of antibiotics in livestock production for therapeutic, prophylactic, and, in some cases, growth-promoting purposes. When these drugs are misused or when mandatory withdrawal periods are not observed before slaughter or milk collection, residual compounds may persist in food products such as meat, milk, eggs, and fish [4, 31]. This issue is particularly pronounced in intensive production systems and in regions where regulatory frameworks are weak or inadequately enforced [2].

Beyond their mere presence, ARs exhibit considerable variability across geographical regions, food categories, and antibiotic classes, reflecting differences in veterinary practices, regulatory enforcement, production systems, and surveillance capacities. These variations indicate that AR contamination is influenced not only by antibiotic usage patterns but also by disparities in monitoring infrastructure and regulatory compliance. Consequently, contamination levels vary substantially across countries and production sectors, underscoring the need for context-specific control measures and harmonized surveillance programs.

A comparative synthesis of global prevalence patterns of ARs in foods of animal origin is presented in Table 1[3, 5, 9, 22, 40–47].

Numerous studies worldwide have confirmed the presence of ARs in food products, often exceeding established MRLs. For example, in Nigeria, more than 80% of meat samples tested positive for oxytetracycline residues, frequently exceeding safe thresholds [40]. In Pakistan, approximately 40% of milk samples contained tetracyclines and sulfonamides [3], whereas 32% of beef samples in Ethiopia exceeded MRLs for tetracycline residues [5]. Similarly, in Bangladesh, 28% of poultry meat samples were contaminated with ciprofloxacin residues [22].

These findings indicate that contamination is not only widespread but also heterogeneous, with markedly higher prevalence rates observed in low- and middle-income countries, where enforcement of withdrawal periods and veterinary oversight remains limited [2, 11]. In contrast, high-income regions tend to exhibit lower but persistent contamination levels, reflecting stronger surveillance systems but incomplete elimination of residues. These regional disparities underscore the importance of strengthening residue-monitoring programs and harmonizing regulatory practices at the international level.

Several factors contribute to the persistence of ARs in food systems. Mismanagement of antibiotics, including overdosing and failure to comply with withdrawal periods, remains the primary cause [2]. Inadequate monitoring systems and limited awareness among farmers further exacerbate the problem [11, 48]. In addition, the physicochemical properties of antibiotics strongly influence their persistence. Certain classes, particularly tetracyclines and sulfonamides, exhibit high thermal stability, allowing them to withstand common processing procedures. Although pasteurization may reduce residue concentrations in milk, complete elimination is not achieved, and cooking has limited effects on thermally stable compounds [6, 12].

Overall, the global distribution of ARs reveals a consistent pattern: higher contamination levels in regions with limited regulatory enforcement and lower yet persistent levels in highly regulated systems. Importantly, the current body of literature remains largely descriptive, with relatively few comparative analyses across geographical regions and food categories. Furthermore, the absence of standardized risk-ranking systems for antibiotic classes based on their technological and microbiological impacts represents a major gap in both research and policy development.

These findings highlight the importance of addressing ARs at their source through improved antibiotic stewardship, stricter enforcement of withdrawal periods, and strengthened surveillance systems. Although technological innovations, including residue-tolerant starter cultures and alternative farming practices, offer promising opportunities, their successful implementation will require coordinated efforts among governments, regulatory agencies, industry stakeholders, and researchers [19, 21]. Ultimately, effective control of ARs is essential not only for protecting public health but also for maintaining food quality, ensuring technological reliability, and preserving the sustainability of animal-derived food systems [1, 41].

The presence of ARs in foods of animal origin represents a major technological challenge for fermentation-based food systems. Fermentation is a highly regulated biological process driven by complex microbial consortia, including LAB, yeasts, and, in some cases, halophilic microorganisms, which transform raw substrates into stable, safe, and organoleptically desirable products such as yogurt, cheese, fermented meats, and fish sauces [14–16]. Even trace concentrations of ARs can disrupt this delicate microbial balance, leading to fermentation failure, product defects, and reduced process reliability [12, 31].

From a mechanistic perspective, the technological risks associated with ARs arise from their direct interference with microbial metabolic pathways. Different antibiotic classes exert specific inhibitory effects: β-lactams disrupt cell wall synthesis, tetracyclines inhibit protein synthesis, and sulfonamides interfere with folate metabolism, collectively impairing microbial growth, enzyme production, and stress adaptation. These effects are particularly critical for starter cultures, whose metabolic activities govern acidification, proteolysis, and flavor development [3, 20]. Table 2 summarizes the major classes of antibiotics that may be present as residues in animal-derived raw materials. For each class, the mechanism of action, target microorganisms, impact on fermentation processes, potential product defects, and associated technological risk level are presented [3, 6, 12, 20, 31, 43, 45, 46].

At the core of fermentation processes lies the activity of starter cultures, which ensure controlled acidification and product consistency. ARs interfere with these processes by inhibiting microbial growth and metabolic activity. For example, penicillin residues at concentrations as low as 0.005 mg/L have been shown to delay acidification during yogurt production, demonstrating that even sub-MRL concentrations can significantly affect fermentation performance [31].

Despite these observations, a major limitation of the current literature is the lack of standardized dose-response relationships defining the threshold concentrations at which fermentation inhibition occurs. Although several studies have reported inhibitory effects of ARs at sub-MRL concentrations, available data remain fragmented and inconsistent among antibiotic classes and fermentation systems. For instance, β-lactams have been shown to inhibit LAB at concentrations as low as 0.005 mg/L, whereas comparable thresholds for tetracyclines and sulfonamides remain poorly characterized. This lack of harmonized dose-response information limits the development of predictive models for fermentation failure and represents a critical barrier to risk assessment and regulatory standardization.

The detection and monitoring of ARs in foods are essential for safeguarding public health, ensuring regulatory compliance, and maintaining the technological integrity of food-processing systems [31]. Antibiotics used in animal production frequently persist in food matrixes such as milk, meat, and fish, necessitating reliable analytical approaches for their identification and quantification [12]. Beyond simple detection, effective monitoring systems must integrate analytical performance, sampling strategies, validation protocols, and surveillance capacity, particularly across diverse regulatory and economic settings [11]. Accurate detection and quantification of ARs in food products require the use of reliable analytical techniques with varying levels of sensitivity, specificity, cost, and operational complexity. Table 3 presents a comparative analysis of the major analytical methods currently employed for the detection of ARs in foods, highlighting their principles, target compounds, analytical performance, practical advantages and limitations, as well as their suitability for implementation in low- and middle-income countries [6, 11, 12, 19, 21, 31, 48].

Mitigating ARs in foods requires a comprehensive and integrated strategy that addresses the problem at multiple levels, from primary production to final consumption. Effective mitigation should not only target the root causes of contamination but also incorporate monitoring systems and technological interventions to ensure food safety and maintain technological reliability [12, 31]. To facilitate implementation and improve clarity, mitigation strategies can be categorized into three complementary levels: primary prevention, secondary detection, and tertiary technological intervention. A summary of these approaches is presented in Table 4[1, 4, 11, 12, 19, 21, 31, 48].

Primary prevention: Responsible antibiotic use and animal husbandry

The most effective approach for reducing ARs is prevention at the source through responsible antibiotic use in animal production. Antibiotics should be restricted to therapeutic applications and should not be routinely used for growth promotion or prophylaxis [1]. Strict adherence to withdrawal periods is essential to ensure that residues are eliminated from animal tissues before products enter the food chain [11].

Improved animal husbandry practices further contribute to reducing antibiotic dependence. Enhanced hygiene, optimized nutrition, and vaccination programs have been shown to reduce infection rates and decrease the need for antibiotic interventions [21, 48]. However, implementation remains challenging in smallholder production systems because of economic constraints, limited access to veterinary services, and inadequate awareness. These limitations highlight the need for context-specific interventions suitable for both industrial and resource-limited settings.

Secondary detection: Monitoring and surveillance systems

Monitoring systems play a critical role in identifying contamination and preventing ARs from entering the food supply. Routine sampling and analytical testing facilitate early detection and regulatory enforcement [12]. Advances in analytical technologies, including HRMS and biosensors, have substantially improved detection capabilities [19, 21]. In addition, rapid screening tools enable on-site testing and support real-time decision-making in food production systems [11].

Despite these advancements, surveillance systems remain unevenly distributed worldwide. In low- and middle-income countries, limited infrastructure, high operational costs, and shortages of technical expertise hinder effective monitoring programs, emphasizing the need for affordable and scalable detection technologies [6, 48].

The challenges posed by ARs in food systems, particularly in fermentation-based products, necessitate innovative, multidisciplinary, and scalable solutions. Although several mitigation strategies have been proposed, their feasibility, accessibility, and long-term sustainability remain uncertain, particularly across diverse economic and regulatory settings [12, 31]. To address these limitations, future research and policy initiatives should adopt a structured roadmap encompassing short-, medium-, and long-term priorities while explicitly addressing critical knowledge gaps and technological barriers.

Short-term priorities: Improving detection and surveillance

In the short-term, strengthening detection and monitoring systems remains a major priority. Advanced analytical technologies such as LC-MS, HRMS, and biosensor platforms offer high sensitivity and specificity for AR detection [19, 21]. However, their widespread implementation is constrained by high costs and technical complexity, particularly in low- and middle-income countries [11, 45].

Future efforts should therefore focus on the development of miniaturized, cost-effective, and user-friendly detection technologies, including portable biosensors and rapid diagnostic kits suitable for field applications. In addition, strengthening surveillance infrastructure and promoting harmonized sampling protocols will be essential for improving the reliability and comparability of monitoring programs.

Medium-term priorities: Technological and biological innovations

At the processing level, one promising approach is the development of residue-tolerant or robust starter cultures capable of maintaining fermentation performance in the presence of low concentrations of ARs [12, 31]. Nevertheless, this strategy requires careful evaluation because it may contribute to the selection or dissemination of AMR genes within fermentation ecosystems. Therefore, comprehensive risk assessments involving genomic and phenotypic analyses are essential before large-scale implementation.

Alternative approaches, including probiotics, prebiotics, and phytogenic compounds, have shown promise for reducing antibiotic use at the production stage [6, 12]. However, their scalability, long-term efficacy, and regulatory acceptance remain inadequately characterized, highlighting the need for longitudinal studies and validation across multiple production systems.

Long-term priorities: Integration of emerging technologies

In the long-term, emerging technologies are expected to revolutionize AR monitoring and control. Artificial intelligence (AI) and machine-learning approaches can be incorporated into predictive models for contamination risk assessment and fermentation process monitoring. Likewise, metagenomic approaches offer powerful tools for characterizing microbial communities and tracking the resistome in fermented food systems, thereby providing deeper insights into AR–microbiome interactions.

Furthermore, nanotechnology-based biosensors and CRISPR-based detection systems represent promising innovations for the ultrasensitive and rapid detection of ARs. However, successful adoption of these technologies will require standardization, validation, and cost reduction to ensure accessibility across diverse production systems.

Despite increasing interest in ARs, several important knowledge gaps remain:

1. Lack of standardized dose-response thresholds linking AR concentrations with fermentation inhibition.

2. Limited longitudinal studies evaluating the effects of ARs on fermentation microbiomes.

3. Insufficient information regarding the co-occurrence of ARs and AMR genes in fermented foods.

4. Limited integration of advanced analytical tools, including AI and metagenomics, into routine monitoring systems.

5. Scarcity of scalable and economically viable solutions suitable for artisanal and smallholder production systems.

6. Inadequate comparative studies among dairy, meat, and aquatic fermentation systems.

7. Limited understanding of the long-term ecological consequences of chronic low-level AR exposure on fermentation microbiota and food quality.

Overall, future responses to ARs should avoid reliance on isolated solutions. Instead, an integrated framework combining technological innovation, preventive veterinary practices, accessible monitoring tools, and harmonized regulatory systems is required [11, 31]. Such a framework must also account for economic constraints, regional disparities, and consumer behavior to ensure effective and sustainable implementation.

A One Health-oriented approach integrating veterinary medicine, food technology, microbiology, public health, and regulatory science will be essential for addressing the multifaceted challenges associated with ARs. Only through coordinated, multidisciplinary, and context-specific strategies can ARs be effectively controlled, thereby safeguarding food safety, preserving fermentation technologies, and ensuring the long-term sustainability of global food systems.

ARs in foods of animal origin represent a complex challenge that extends beyond their well established public health implications and directly affects the technological performance and sustainability of fermentation-based food systems. The evidence synthesized in this review demonstrates that ARs are widely distributed across dairy, meat, egg, and aquaculture products, with contamination levels varying according to geographical region, production system, and regulatory capacity. Different antibiotic classes, particularly β-lactams, tetracyclines, sulfonamides, fluoroquinolones, and chloramphenicol, interfere with microbial metabolism and impair key fermentation processes, resulting in delayed acidification, reduced proteolysis, altered flavor development, fermentation failure, and increased risks of pathogen survival and biogenic amine accumulation. The review further highlights the strengths and limitations of currently available analytical approaches and emphasizes the importance of integrating preventive, monitoring, and technological interventions to minimize the occurrence and consequences of AR contamination.

From a practical perspective, effective management of ARs requires responsible antibiotic use, strict compliance with withdrawal periods, improved animal husbandry practices, strengthened surveillance systems, and implementation of rapid and reliable detection technologies. In addition, the development of residue-tolerant starter cultures, innovative biosensor platforms, and digital monitoring tools may provide valuable opportunities for improving fermentation reliability and food safety. Harmonization of international regulatory frameworks and enhancement of monitoring capacities, particularly in low- and middle-income countries, are equally essential for reducing contamination and facilitating safe global trade.

A major strength of this review lies in its integrative approach, which combines microbiological, pharmacological, technological, and regulatory perspectives to provide a comprehensive understanding of the mechanisms and consequences of AR contamination in fermented foods. Unlike previous studies that have focused predominantly on toxicological aspects and AMR, the present review emphasizes the technological dimension of ARs and highlights their implications for fermentation performance and product quality across different food sectors.

Nevertheless, several limitations should be acknowledged. Available evidence remains fragmented, and differences in study design, analytical methodologies, and surveillance capacities limit direct comparisons among studies. Furthermore, standardized dose-response thresholds for fermentation inhibition are lacking, and information regarding the long-term effects of low-level AR exposure on food microbiomes and fermentation ecosystems remains limited. In addition, relatively few studies have systematically compared industrial, artisanal, and traditional fermentation systems.

Future research should prioritize the establishment of standardized fermentation inhibition thresholds, long-term investigations of AR–microbiome interactions, and comparative studies across diverse fermentation systems. Greater integration of advanced technologies, including AI, metagenomics, nanobiosensors, and CRISPR-based detection platforms, may substantially improve monitoring and risk assessment. Further studies are also required to develop scalable and economically sustainable mitigation strategies applicable to both industrial and smallholder production systems.

Overall, ARs should be recognized not only as contaminants of public health concern but also as important determinants of technological performance in fermented foods. Addressing this challenge requires coordinated, multidisciplinary, and One Health-oriented approaches integrating veterinary medicine, food microbiology, analytical sciences, food technology, and regulatory policy. Such efforts will be essential for safeguarding food quality and safety, preserving fermentation technologies, and ensuring the long-term sustainability and resilience of global food systems.

All data supporting the findings and conclusions of this review are included within the manuscript.

The authors declare that generative artificial intelligence (AI) tools were used solely to improve language, grammar, and readability during manuscript preparation. All scientific content and conclusions were developed and verified by the authors. The authors take full responsibility for the accuracy, integrity, and originality of the work presented, and no AI tool was listed as an author.

MMJA: Conceived and designed the study, coordinated the project, conducted the literature search, analyzed the data, and drafted the original manuscript. BZC, PK, IK, AKLD, and NBAT: Contributed to literature collection, data interpretation, and manuscript revision. EV, NS, MM, NZ, and MA: Participated in critical review, scientific validation, and editing of the manuscript. All authors have read, reviewed, and approved the final version of the manuscript.