Safety, Efficacy, and Impact on Gut Microbial Ecology of a Subspecies LMG11588 Supplementation in Healthy Term Infants: a Randomized, Double-blind, Controlled Trial in the Philippines

Introduction: subspecies infantis () may play a key role in infant gut development. This trial evaluated safety, tolerability, and efficacy of LMG11588 supplementation.

Methods: This randomized, placebo-controlled, double-blind study conducted in the Philippines included healthy breastfed and/or formula-fed infants (14-21 days old) randomized for 8 weeks to a control group (CG;  = 77), or any of two experimental groups (EGs): low (Lo-EG; 1*10 CFU/day;  = 75) or high dose (Hi-EG; 1.8*10 CFU/day;  = 76). Primary endpoint was weight gain; secondary endpoints included stooling patterns, gastrointestinal symptoms, adverse events, fecal microbiome, biomarkers, pH, and organic acids.

Results: Non-inferiority in weight gain was demonstrated for Hi-EG and Lo-EG vs. CG. Overall, probiotic supplementation promoted mushy-soft stools, fewer regurgitation episodes, and increased fecal acetate production, which was more pronounced in the exclusively breastfed infants (EBF) and positively correlated with abundance. In EBF, fecal pro-inflammatory cytokines (IL-1 beta, IL-8) were reduced. Strain-level metagenomic analysis allowed attributing the increased abundance of in EGs versus CG, to LMG11588 probiotic colonization. Colonization by autochthonous strains was similar between groups.

Discussion: LMG11588 supplementation was associated with normal infant growth, was safe and well-tolerated and promoted a -rich microbiota driven by LMG11588 colonization without disturbing the natural dispersal of autochthonous strains. In EBF, supplementation stimulated microbial metabolic activity and beneficially modulated enteric inflammation.