INTRODUCTION

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].

Figure 1: Conceptual framework illustrating the pathways and technological impacts of antibiotic residues (ARs) in animal-derived fermented foods. The figure depicts the progression from antibiotic use in animal production to residue contamination of food matrixes, subsequent microbial inhibition, disruption of fermentation processes, and the resulting consequences for food quality, food safety, economic performance, and public health. In addition, the framework incorporates potential mitigation strategies that can be implemented at different stages of the production chain [4, 21, 30, 39].