Comparison of Two Active Doses of Microencapsulated Lacticaseibacillus rhamnosus GG in a Yoghurt Drink on Gut Microbiome Profiles in Healthy Adults: A Randomised, Double-Blind Crossover Trial

Probiotic efficacy may depend on reliable intestinal exposure, yet clinical evidence linking delivery engineering to measurable microbiome responses in humans remains limited. We compared two active doses of microencapsulated Lacticaseibacillus rhamnosus GG in 26 healthy adults in a randomised, double-blind, two-period crossover trial. Participants received 2 × 109 CFU/day (2BN) and 6 × 109 CFU/day (6BN) for 28 days each in a yoghurt drink, separated by a 14-day washout. Gastrointestinal metrics, tolerance, bowel-habit metrics, and the measured biomarkers remained stable across both doses. By metagenomics, L. rhamnosus was detected in stools in 8/23 participants at baseline, 12/23 participants after 6BN, and 10/23 after 2BN. These data represent marginal prevalence counts and does not establish individual acquisition, viability, persistence or colonisation. Species-level PERMANOVA on Aitchison distances showed a significant within-period microbiome shift during 6BN that was not observed during 2BN. There were directional changes in commensal anaerobic taxa and metagenomic functional modules related to vitamin/cofactor biosynthesis, polyamine biosynthesis, glycogen degradation, multidrug-resistance efflux pumps, and tetrahydrobiopterin biosynthesis. Microencapsulated L. rhamnosus GG was safe and well tolerated at both doses.