Effects of Human Lactoferrin (Effera®) at Two Doses Versus Bovine Lactoferrin on the Adult Gut Microbiome and Fecal Short-Chain Fatty Acids: A Randomized, Double-Blind Trial

Human lactoferrin (hLF) is a glycoprotein of commercial interest as a food ingredient for gut health. This exploratory analysis compared the effects of Helaina hLF (effera®), produced by Komagataella phaffii, and bovine LF (bLF) on the adult gut microbiome and fecal metabolites. In a randomized, double-blind, parallel-arm, controlled trial, 66 healthy adults received either high-dose effera® (3.4g/day), low-dose effera® (0.34g/day), or bLF (3.4g/day) supplementation for 28 days. Fecal samples were analyzed for microbial diversity, taxonomic shifts, and volatile fatty acids. Alpha-diversity remained stable across all groups. At the phylum level, effera® was associated with decreases in Bacillota and Verrucomicrobiota and genus-level increases in Lachnospira, Paraprevotella, and Faecalibacterium, while bLF increased Bacteroidota and Roseburia. Both treatments decreased Blautia and Dorea. bLF increased absolute total SCFAs and branched-chain fatty acids, while effera® produced proportional increases in SCFAs and acetate. In healthy adults, effera® supplementation promoted a proportional increase in acetate and supported potentially beneficial taxa while maintaining microbial diversity, without disrupting community structure (clinicaltrials.gov: NCT06012669).