Silymarin, an extract from fruits and seeds of the milk thistle Silybum marianum (L.) Gaertn., is basically a flavonolignan complex. Although its composition may vary depending on the source, 70% is made up of the flavonolignans silybin A and B, isosilybin A and B, silychristin A and B, silydianin and the flavanol taxifolin. Minor components include the flavonolignan isosilychristin and the corresponding 2,3-dehydro derivatives of various flavonolignans, such as 2,3-dehydrosilybin, 2,3-dehydrosilychristin and 2,3-dehydrosilydianin. Meta-analyzes of clinical trials show that silymarin plays an important complementary role in the treatment of non-alcoholic fatty liver disease, especially in terms of lowering levels of alanine and aspartate transaminases. It has been shown to reduce hepatic fibrosis markers and serum levels of transforming growth factor beta-1 (TGF-β1), tumor necrosis factor alpha (TNF-α), and interleukin 6 (IL-6) in patients with chronic hepatitis B. Furthermore, it decreased total cholesterol and low-density lipoprotein (LDL) levels while increasing high-density lipoprotein (HDL) levels in hyperlipidemic individuals. The hepatoprotective effects may be attributed to influencing metabolic pathways to increase hepatic glutathione synthesis and cysteine availability, leading to higher antioxidant lipid defense in the liver or altering growth factor-β-mediated cell signaling pathways, as demonstrated by in vivo studies. In vitro studies suggest that silymarin may inhibit the proliferation of CD4 + cells, affect the pathways of NF-κB activation or inhibit the production of pro-inflammatory cytokine. The bioavailability of silymarin components after oral administration is in the range 20-50% due to low water solubility, extensive phase II metabolism, low permeability through intestinal epithelial cells and involvement of efflux transporters. The flavonoids and flavonolignans undergo extensive enterohepatic circulation, with up to 80% of the absorbed silymarin constituents reintroduced into the intestine via bile. In the large intestine, these compounds are subject to extensive microbial metabolism. The biological activity of the parent compounds versus their microbial degradation products is currently a matter of contentious debate among experts. The ability of the colon microbiota to metabolize (poly)phenols varies considerably from person to person, as shown by previous studies, due to differences in microbiota composition. This composition is influenced by numerous factors, including diet, general lifestyle, intake of probiotics and antibiotics, and environmental conditions, Additionally, significant changes in microbiota composition have been observed in individuals over the age of 65 years. Consequently, the ability of the aging population to metabolize and utilize (poly)phenols and other dietary components may be compromised. From another perspective, recent studies have shown that dietary intake of (poly)phenols can alter the composition of the gut microbiota. Multi-omic techniques have emerged as powerful tools in biomedical research, integrating data from multiple omics layers to provide a comprehensive understanding of complex biological systems. These approaches have advanced knowledge in personalized medicine and disease pathogenesis. The integration of metabolomics and sequencing has further deepened our understanding of the relationships between microbiota and metabolites. This study aims to elucidate the interactions between silymarin and the gut microbiome in aging populations using a multi-omics approach (NGS, 1 H-NMR, and LC-MS). By employing in vitro batch incubations with feces from 20 individuals, we examined age-related effects and individual microbial profiles on silymarin catabolism and its impact on microbial composition and metabolic capacity. The goal was to understand these interactions to develop age-specific nutritional strategies in relation to (poly)phenol intake.