Mutual Interactions of Silymarin and Colon Microbiota in Healthy Young and Healthy Elder Subjects

Scope This multi-omic study investigates the bidirectional interactions between gut microbiota and silymarin metabolism, highlighting the differential effects across various age groups. Silymarin, the extract from Silybum marianum (milk thistle), is commonly used for its hepatoprotective effects. Methods and results An in vitro fermentation colon model was used with microbiota from 20 stool samples obtained from healthy donors divided into two age groups. A combination of three analytical advanced techniques namely next-generation sequencing, 1H-NMR and LC-MS was used to determine silymarin microbial metabolites over 24 h, overall metabolome and microbiota composition. Silymarin at a low diet-relevant dose of 50 µg/mL significantly altered gut microbiota metabolism, reducing short-chain fatty acid (acetate, butyrate, propionate) production, glucose utilization, and increasing alpha-diversity. Notably, the study revealed age-related differences in silymarin catabolism. Healthy elderly donors (70–80 years) exhibited a significant increase in a specific catabolite associated with Oscillibacter sp., whereas healthy young donors (12–45 years) showed a faster breakdown of silymarin components, particularly isosilybin B, which was associated with higher abundance of Faecalibacterium and Erysipelotrichaceae UCG-003. Conclusion This study provides insights into microbiome functionality in metabolizing dietary flavonolignans, highlighting implications for age-specific nutritional strategies and advancing our understanding of dietary (poly)phenol metabolism.