## 4 Discussion  
The evaluation of the antimicrobial potential of _Humulus lupulus_ (hop) extracts and compounds has consistently highlighted significant variability, arising from differences in bacterial strains, extraction methods, experimental conditions, and the intrinsic diversity of phytoconstituents. The establishment of evidence-based practices, including standardized protocols for assessing antimicrobial activity, is critical for the scientific community to reliably compare, and interpret these findings. Without standardization, evaluating results across studies remains challenging, limiting the translation of hop-derived antimicrobial agents into clinical or commercial applications [56,68]. This systematic review and meta-analysis aimed to combine all available data to deliver a comprehensive, statistically rigorous synthesis of the antimicrobial activity of _Humulus lupulus_ extracts and purified compounds, thereby informing future studies and practical applications. While hops have long been used for their preservative role in brewing, and their pharmacological potential has gained increasing attention, the methodologically diverse nature of existing studies has limited the development of a consolidated view of their antimicrobial efficacy. By integrating MIC data across 450 individual studies and 55 microbial strains, we contribute a much-needed evidence-based framework that enhances the reliability and reproducibility of antimicrobial findings related to hop-derived substances. Our meta-analysis indicated substantial differences in the antimicrobial efficacy among hop-derived compounds. Specifically, we found pronounced variability in activity between chalcones such as xanthohumol and flavanols like catechin. Xanthohumol consistently showed potent antimicrobial effects, notably against _Staphylococcus epidermidis_ (with MIC value 1.37 \(\upmu\)g/mL) and _Clostridium_ species (MIC value 32.6 \(\upmu\)g/mL), with significantly lower MIC values compared to catechin, which exhibited minimal activity (MIC value 1200 \(\upmu\)g/mL against _Bacillus subtilis_). Similarly, alpha acids (humulone) demonstrated markedly different antimicrobial profiles compared to beta acids (lupulone), with lupulone generally showing higher potency across multiple microbial species. These findings are in accordance with other reviews highlighting the broad-spectrum antimicrobial and biofilm-inhibiting properties of prenylated chalcones and bitter acids [1,10]. These compound-specific differences underscore the critical importance of chemical structure and functional groups in antimicrobial potency. For instance, the prenylated chalcone structure of xanthohumol, which facilitates cellular membrane penetration, differs substantially from the less effective non-prenylated flavan-3-ol structure of catechin [24,25]. Similarly, structural distinctions between alpha and beta acids--primarily in side-chain composition and prenylation--directly influence their respective antimicrobial activities. Additionally, we observed significant strain-specific variations in antimicrobial susceptibility, highlighting the complexity of microbial responses and reinforcing the need for careful strain selection when evaluating antimicrobial agents. In addition, hydroalcoholic extracts exhibited more consistent antimicrobial performance than CO2 extracts, which displayed highly variable outcomes depending on the tested microorganism. Because alpha and beta acids constitute more than 50% of a supercritical fluid-extracted hop extract, its antiproliferative effects are largely driven by bitter acids [36,51]. Given that beer, originally, is the hydroalcoholic solvent for dry hops, data coming from hydroalcoholic extracts are expected to be of more practicability. However, it is also quite a common practice for beer manufacturers to add condense, CO2-based (SFE) extracts in bulk beer preparations [6] and [GmbH & Co. KG.]