## 3 Results
### Meta-Analysis of MIC Values of Changes of Hop Compounds and Extracts  
A persistent challenge in evaluating the antimicrobial activity of hop-derived extracts lies in the considerable variability introduced by multiple factors. One major concern is determining which bacterial species and strains most accurately reflect the true antimicrobial potential, as susceptibility can vary widely even within a single species. At the same time, hop extracts contain a complex mixture of bioactive compounds, each present at different concentrations that can be significantly influenced by the genetic background [49], the extraction method and the solvent used. These variables complicate interpretation, as changes in extraction parameters may favor the presence of certain compounds while minimizing others. Therefore, we chose to conduct a meta-analysis and include a broad panel of all bacterial strains ever tested for hop compounds or extracts. To better understand their specific contributions to antimicrobial activity, we stratified our meta-analysis according to the two major different classes of natural compounds, the flavonoids, that are polyphenols, and the bitter acids that are prenylated acylphloroglucinol derivatives. As shown in Figure 3A, Table 2, and Supplementary Figure S1A,C, meta-analysis of MIC values of flavonoids and bitter acids, for 24 h of treatment, resulted in a variety of effectiveness depending on the species. However, in most of the cases, flavonoids exert better antimicrobial activity compared to bitter acids when tested in the same bacteria species and strains such as for _Staphylococcus aureus_ (13.61 as opposed to 80.07 ug/mL), _Staphylococcus epidermidis_ (1.37 versus 10.50 ug/mL), _Streptococcus salivarius_ (23.33 versus 58.75 ug/mL) and _Streptococcus saprophyticus_ (2.33 as opposed to 3.83 ug/mL) (Figure 3A). Although antimicrobial tests for 48 h of treatment were performed in different bacterial species, meta-analysis similarly showed elevated antimicrobial activity of flavonoids compared to bitter acids (Figure 3B, Supplementary Figure S1B,D). \begin{table}
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In order to test the antimicrobial effectiveness of various types of hop extracts against microbial species, a meta-analysis was performed with the MIC values for each type of extract testing the effect on each microbial species. As shown in Figure 4A and Table 2, CO2 (SFE) extracts showed a wide range of activity spanning from being the best antimicrobial agent against _Staphylococcus aureus_ (MIC 6.32 \(\upmu\)g/mL) to the worst antimicrobial agent against _Streptococcus aureus_ (MIC 1667 \(\upmu\)g/mL). A similar high divergence in antimicrobial activity was shown for CO2 extracts for 48 h of treatment time and for different microbial species (Figure 4B and Table 2). Hydroalcoholic extracts exposed a more constant antimicrobial activity spanning from 39.0 (_Staphylococcus aureus_) to 625 \(\upmu\)g/mL (_Pseudomonas aeruginosa_) for 24 h of treatment and from 34.67 (_Streptococcus Salivarius_) to 384 \(\upmu\)g/mL (_Candida albicans_) for 48 h of treatment. Publication bias tests showed that it was more prominent for studies performed for 48 h of incubation (Table 2). Figure 4: Meta-analysis of MIC values for various types of extracts against various microorganisms’ species, for 24 (**A**) and 48 (**B**) hours of incubation. Figure 3: Meta-analysis of MIC values for flavonoids and bitter acids against various microorganisms’ species, for 24 (**A**) and 48 (**B**) hours of incubation.