Polyphenols Nonmonotonically Modulate the Inulin-Driven Gut Microbial Network <i>In Vivo</i>

The interaction between dietary fiber and polyphenols in modulating gut microbiota is complex and not fully understood. This study investigated how the polyphenol structure (complex tannic acid vs simple ferulic acid) and dosage (20-320 mg/kg) modulated the gut microbiota and metabolic profile shaped by a high-dose inulin diet. Our results showed that all treatments were well-tolerated with no observed adverse health outcomes. While polyphenol addition did not cause large-scale shifts in overall microbiota composition, it fundamentally restructured the underlying microbial network. Each polyphenol established a distinct hub species, with <i>Oscillospira</i> for tannic acid and <i>Allobaculum</i> for ferulic acid. This restructuring was accompanied by nonmonotonic dose-response changes in short-chain fatty acid production, an effect attributed to a shifting balance between the polyphenols' trophic and antimicrobial activities. Our findings demonstrate that in a high-fiber context, polyphenols act as subtle modulators, rather than primary drivers, whose structure and dose critically shape the microbiome function.