Effects of Human Lactoferrin (Effera^®) at Two Doses Versus Bovine Lactoferrin on the Adult Gut Microbiome and Fecal...

Human lactoferrin (hLF) is a glycoprotein of commercial interest as a food ingredient for gut health. We conducted an exploratory analysis comparing 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 (HD) effera^® (3.4 g/day), low-dose (LD) effera^® (0.34 g/day), or bLF (3.4 g/day) supplementation for 28 days. Fecal samples collected at Days 0 (baseline), 28, 56, and 84 were analyzed for microbial diversity, taxonomic shifts, and volatile fatty acids (VFA). Alpha-diversity remained stable across all groups. Beta-diversity showed no main effect of treatment; however, bLF was associated with significant visit-related shifts, as assessed by weighted UniFrac. At the phylum level, significant changes associated with effera^® were observed, including decreases in Bacillota (LD) and Verrucomicrobiota (HD), and notable genus-level increases in Lachnospira, Paraprevotella, and Faecalibacterium (HD), while bLF was associated with an increase Bacteroidota at the phylum level and with an increase in the genus Roseburia. Both effera^® and bLF were associated with decreases in Blautia and Dorea. VFA analysis revealed that bLF increased absolute concentrations of total short-chain fatty acids (SCFAs) and branched-chain fatty acids (BCFAs); both effera^® treatments produced proportional changes in SCFAs as a percent of total VFA, acetate, and individual BCFAs. In healthy adults, effera^® supplementation promoted a proportional increase in acetate and supported potentially beneficial taxa while maintaining microbial diversity, without disrupting community structure. As a pre-specified exploratory outcome, microbiome and VFA findings should be interpreted as hypothesis-generating. (clinicaltrials.gov: NCT06012669).