Dynamic changes in the metabolome and microbiome during Citrus depressa Hayata liquid fermentation

Citri Reticulatae Pericarpium (CRP) is a common traditional Chinese herbal medicine, valued for its multi-bioactivity. However, its processing time, environment, and microorganisms all affect its quality and bioactivity. To address this, the study replaced solid-state fermentation with liquid fermentation using microorganisms and isolated Bacillus amyloliquefaciens, respectively. This aimed to discover a more stable processing method and examine metabolite-micobiota correlations. Non-targeted metabolomics identified 70 differential metabolites, focusing on amino acids, polymethoxyflavones (PMFs), and carbohydrates. Long-read sequencing showed a shift in dominant bacterial genera from Lactobacillus to Pediococcus, then to Clostridium. Spearman analysis revealed a positive correlation between specific Clostridium species and PMFs production. B. amyloliquefaciens fermentation notably increased PMFs content without reducing hesperidin levels, suggesting its potential as an alternative processing method. This study offers valuable insights into metabolome-microbiome interactions for future biotransformation research.