# Plant-Derived Phytobiotics as Emerging Alternatives to Antibiotics Against Foodborne Pathogens
## 7 Key Knowledge Gaps  
Although the topic of using phytobiotics against foodborne pathogens has been the subject of a considerable amount of research over the years, there are still some knowledge gaps waiting to be filled. Completing them through targeted research is essential for the effective use of plant-derived phytobiotics against foodborne pathogens. Future research should focus on understanding the mechanisms of action, interactions between phytochemicals, in vivo efficacy, resistance development, standardization, safety, and regulatory challenges to realize the full potential of these natural antimicrobials. While many studies have reported antimicrobial properties of plant extracts, the specific mechanisms by which these phytochemicals inhibit pathogens remain unclear. For example, antimicrobial activity of various phytochemicals against pathogens such as _Salmonella_, _E. coli_, and _Listeria_ has been observed, but the exact biochemical pathways involved in this action need further clarification [312; 313]. Also, the potential for pathogens to develop resistance to phytobiotics is not well documented. Long-term studies are required to assess whether long-,term use of these compounds could lead to resistance, similar to that seen with conventional antibiotics [103; 313; 314]. In addition, the interactions between different phytochemicals in a single plant extract and their combined effects on pathogens are not well explored. Rather, single phytobiotics are being studied, while understanding these interactions might help formulate more effective combinations of phytobiotics [103; 262]. Moreover, most of the research on this topic has been conducted in vitro, and there is a significant gap in understanding how these phytobiotics work in vivo, particularly in complex food matrices and in the human body. For example, while some plant extracts have shown promising results in vitro, their efficacy in real food systems and their bioavailability in humans require further research [103; 313; 315]. Comprehensive studies on the safety and potential toxicity of phytobiotics are limited. To ensure that they are fully safe for human consumption, there is still a need for research aimed at assessing their safety, efficacy, and potential interactions with conventional treatments. Furthermore, knowledge should be supplemented with an understanding of the long-term effects of the consumption of these compounds, especially at higher doses. Evaluating their impact on human health and the microbiome is crucial to establishing guidelines for their inclusion in food systems [313; 315]. otics in the food industry depends on overcoming a number of technological, economic, and regulatory constraints (Table 6). In recent years, new strategies to improve the stability and bioavailability of phytobiotics have been intensively developed, including nanoencapsulation techniques, the formation of complexes with polysaccharides, and the use of modern extraction methods such as supercritical CO\({}_{2}\) extraction or subcritical water extraction. The use of polymeric nanocarriers not only increases the solubility and persistence of bioactive compounds but can also reduce their toxicity and improve their efficacy in biological environments [316]. In the context of enhancing the biological activity of phytobiotics, strategies for combining them with other natural components, such as postbiotics, bacteriocins, or secondary metabolites of probiotic microorganisms, are also important. The interaction of these compounds can lead to synergistic effects, increasing the effectiveness of biocontrol and limiting the growth of pathogens without the need for synthetic preservatives [317]. The need for in-depth research on such interactions is a current and promising direction of scientific development.