Polyphenols Nonmonotonically Modulate the Inulin-Driven Gut Microbial Network In Vivo.

All polyphenol treatments were well-tolerated with no observed adverse health outcomes across the tested dosage range.

• Dosage range tested was 20–320 mg/kg body weight
• Both tannic acid (complex polyphenol) and ferulic acid (simple polyphenol) were tested
• All treatments were administered in the context of a high-dose inulin diet
• No adverse health outcomes were observed for any treatment group

Polyphenol addition did not cause large-scale shifts in overall microbiota composition but fundamentally restructured the underlying microbial network.

• Both tannic acid and ferulic acid were tested at multiple doses (20–320 mg/kg)
• Overall microbiota composition metrics did not show large-scale changes
• The microbial co-occurrence or interaction network was fundamentally restructured despite the lack of gross compositional change
• The restructuring was polyphenol-structure-dependent

Each polyphenol established a distinct hub species in the microbial network, with Oscillospira for tannic acid and Allobaculum for ferulic acid.

• Tannic acid, the complex polyphenol, established Oscillospira as the hub species
• Ferulic acid, the simple polyphenol, established Allobaculum as the hub species
• Hub species identity was dependent on polyphenol chemical structure
• This finding indicates that polyphenol structure critically shapes which microbial taxa become network keystones

Polyphenols induced nonmonotonic dose-response changes in short-chain fatty acid (SCFA) production.

• SCFA production did not increase or decrease linearly with polyphenol dose
• The nonmonotonic response was observed across the dosage range of 20–320 mg/kg
• The effect was attributed to a shifting balance between the polyphenols' trophic and antimicrobial activities
• At different doses, polyphenols may promote microbial growth (trophic effect) or inhibit it (antimicrobial effect), resulting in non-linear SCFA outputs

Polyphenol structure and dose critically shape microbiome function in a high-fiber dietary context, with polyphenols acting as subtle modulators rather than primary drivers.

• The study used a high-dose inulin diet as the dietary fiber background
• Polyphenols modulated the inulin-driven gut microbial network rather than independently driving compositional change
• Both polyphenol structure (complex tannic acid vs simple ferulic acid) and dosage (20–320 mg/kg) were identified as critical determinants of microbiome function
• The interaction between dietary fiber and polyphenols was described as complex and not fully understood prior to this study