TECHNOLOGICAL RISKS OF ARS IN FERMENTED ANIMAL-DERIVED FOODS

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.

Antibiotic class | Mechanism of action | Target microorganisms | Fermentation impact | Product defects/consequences | Technological risk level | References
β-lactams (e.g., penicillin) | Inhibition of cell wall synthesis | LAB | Delayed or inhibited acidification; reduced starter culture growth | Poor curd formation, weak texture, off-flavors, and reduced shelf life | High | [12, 20]
Tetracyclines | Inhibition of protein synthesis (30S ribosome) | LAB, spoilage bacteria | Reduced microbial growth and metabolic activity; incomplete fermentation | Slow acidification, spoilage, and accumulation of undesirable compounds | High | [3, 6]
Sulfonamides | Inhibition of folate synthesis | LAB and other bacteria | Impaired microbial metabolism and enzymatic activity | Reduced fermentation efficiency and unstable product quality | Moderate | [6]
Macrolides | Inhibition of protein synthesis (50S ribosome) | LAB | Suppressed microbial growth and enzyme production | Altered flavor development and incomplete fermentation | Moderate–High | [43]
Fluoroquinolones (e.g., ciprofloxacin and enrofloxacin) | Inhibition of DNA gyrase and topoisomerase IV | LAB, halophilic bacteria | Reduced microbial replication and enzymatic activity | Delayed fermentation and weak flavor development in fish products | High | [45, 46]
Chloramphenicol | Inhibition of protein synthesis (50S ribosome) | Broadspectrum microorganisms (LAB and halophiles) | Severe inhibition of fermentation microbiota | Fermentation failure and loss of characteristic sensory properties | High | [46]
Heat-stable antibiotics (e.g., tetracyclines and sulfonamides) | Persistence during processing | LAB and other fermentation microbiota | Continued inhibition during and after heat treatment | Persistent fermentation disruption despite processing | High | [6, 31]

Dairy fermentation systems

The dairy industry is particularly vulnerable to AR contamination due to its reliance on LAB-driven fermentation. In cheese production, β-lactam residues impair enzymatic processes involved in curd formation and ripening, resulting in structural defects, off-flavors, and reduced shelf life [12]. Similarly, delayed acidification during yogurt production compromises both texture and microbial safety [20].

In artisanal systems, such as those reported in Cameroon, penicillin-contaminated milk has been shown to reduce both the yield and quality of fermented dairy products [42]. These effects are often more pronounced in artisanal and traditional systems, where fermentation depends on spontaneous microbiota rather than standardized starter cultures, rendering them more susceptible to AR-induced disruption. In contrast, industrial systems may exhibit partial resilience due to controlled inoculation and process standardization, though they are not immune to fermentation failure.

Meat fermentation systems

Fermented meat products, including sausages and salami, rely on LAB such as _Lactobacillus _sakei and _Pediococcus _acidilactici for acidification, preservation, and flavor development [15]. AR contamination, particularly by tetracyclines, inhibits these microorganisms, leading to incomplete fermentation and increased spoilage risks [6].

Incomplete acidification in meat systems has been directly associated with the accumulation of biogenic amines, including histamine and tyramine, which pose toxicological risks and impair sensory quality [31]. Furthermore, insufficient microbial activity may facilitate the proliferation of spoilage microorganisms and opportunistic pathogens, thereby compromising product safety.

Fish and seafood fermentation systems

Fermented fish products depend on halophilic and proteolytic microorganisms to develop characteristic flavors and textures [16]. However, ARs present in aquaculture-derived raw materials disrupt these microbial processes. For example, enrofloxacin residues in shrimp have been shown to reduce enzymatic activity and impair flavor development during fish sauce production [45, 46].

Unlike terrestrial systems, aquaculture introduces antibiotics directly into the aquatic environment, resulting in continuous exposure and bioaccumulation that may intensify fermentation disturbances. Consequently, seafood fermentation systems are particularly vulnerable to AR-related technological failures.

Safety implications of fermentation disruption

The technological risks associated with ARs extend beyond process inefficiency to critical food safety concerns. Fermentation normally lowers pH, creating an environment unfavorable to pathogenic microorganisms. However, when ARs interfere with acidification, pathogens such as Listeria monocytogenes and Salmonella spp. may survive and proliferate [6, 12]. This disruption not only compromises product safety but also increases the likelihood of foodborne disease outbreaks.

In addition, altered microbial dynamics may favor the emergence and persistence of resistant strains, directly linking technological failure to AMR-related risks.

Economic and industrial impacts

From an industrial perspective, AR contamination represents a significant economic burden. Fermentation failures result in defective batches that must be discarded, leading to material losses and reduced profitability [11]. Products with compromised quality are less competitive and experience lower market acceptance.

In small-scale and traditional systems, these impacts are often even more severe. For example, contaminated milk in African dairy systems has been associated with reduced viability of locally fermented products, directly affecting farmers' income and food security [42]. On a broader scale, AR contamination may also result in trade restrictions and reputational damage, particularly in export-oriented sectors such as aquaculture [46].

Limitations of processing interventions

Attempts to mitigate ARs during processing remain largely ineffective. Heat treatment may reduce the concentrations of certain antibiotics; however, several classes, including tetracyclines and sulfonamides, exhibit considerable thermal stability, enabling them to persist during processing and continue exerting inhibitory effects on fermentation microbiota [6].

Consequently, ARs may remain throughout the fermentation process, continuously suppressing microbial activity [31]. This highlights a major limitation of current mitigation approaches: technological interventions applied during processing cannot fully compensate for upstream contamination, emphasizing the need for preventive strategies at the production stage.

Critical synthesis

Collectively, available evidence demonstrates that ARs constitute a multifaceted technological risk affecting fermentation performance, product quality, food safety, and economic viability. Nevertheless, despite growing recognition of these impacts, current research remains fragmented, with limited integration of microbiological, pharmacological, and technological perspectives.

In particular, the absence of standardized thresholds for fermentation inhibition, the lack of comparative analyses among different fermentation systems, and insufficient attention to artisanal production settings represent major gaps in the literature. Furthermore, limited information is available regarding the long-term effects of low-level AR exposure on fermentation microbiomes and process stability.

Overall, ARs undermine the reliability and sustainability of fermentation-based food production systems. Addressing these challenges requires a comprehensive understanding of their mechanisms of action and technological consequences, which is essential for developing effective mitigation strategies, improving risk assessment, and ensuring the integrity and quality of fermented foods.