This study examined whether effera®, a recombinant human lactoferrin, shifts microbial metabolism and whether resulting fermentation products support epithelial barrier integrity and immune signaling, benchmarked against bovine lactoferrin. Test products underwent simulated upper-gut digestion (INFOGEST 2.0) followed by colonic fermentation in the ex vivo SIFR® platform (Cryptobiotix), using fecal microbiota from six healthy adults across test arms of effera® (50-1000 mg/day), bovine lactoferrin (100, 500, 1000 mg/day), human lactoferrin (1000 mg/day), skimmed milk (1000 mg/day), and a no-substrate control. Fermentation products were applied to Caco-2 intestinal epithelial cell models, measuring short-chain fatty acids (SCFAs), transepithelial electrical resistance (TEER) before/after LPS challenge, CXCL-10, and tight-junction proteins ZO-1 and occludin. effera® produced dose-dependent increases in total SCFAs starting at 50 mg/day, significantly increased TEER versus control in a dose-dependent manner, exceeded bovine lactoferrin on TEER at every matched dose, reduced CXCL-10 across all doses, and supported tight-junction protein expression.
