AUTHOR=Capeding Maria Rosario Z. , Phee Loudhie Cyd M. , Ming Chang , Noti Mario , Vidal Karine , Le Carrou Gilles , Frézal A. , Moll Janne Marie , Vogt Josef Korbinian , Myers Pernille Neve , Nielsen Bjørn Henrik , Boulangé Claire L. , Samuel Tinu Mary , Berger Bernard , Cercamondi Colin Ivano 

TITLE=Safety, efficacy, and impact on gut microbial ecology of a Bifidobacterium longum subspecies infantis LMG11588 supplementation in healthy term infants: a randomized, double-blind, controlled trial in the Philippines

JOURNAL=Frontiers in Nutrition

VOLUME=10

YEAR=2023

URL=https://www.frontiersin.org/journals/nutrition/articles/10.3389/fnut.2023.1319873

DOI=10.3389/fnut.2023.1319873

ISSN=2296-861X

ABSTRACT=<sec id="sec1"><title>Introduction</title><p><italic>Bifidobacterium longum</italic> subspecies infantis (<italic>B. infantis</italic>) may play a key role in infant gut development. This trial evaluated safety, tolerability, and efficacy of <italic>B. infantis</italic> LMG11588 supplementation.</p></sec><sec id="sec2"><title>Methods</title><p>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; <italic>n</italic> = 77), or any of two <italic>B. infantis</italic> experimental groups (EGs): low (Lo-EG; 1*10<sup>8</sup> CFU/day; <italic>n</italic> = 75) or high dose (Hi-EG; 1.8*10<sup>10</sup> CFU/day; <italic>n</italic> = 76). Primary endpoint was weight gain; secondary endpoints included stooling patterns, gastrointestinal symptoms, adverse events, fecal microbiome, biomarkers, pH, and organic acids.</p></sec><sec id="sec3"><title>Results</title><p>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 <italic>B. infantis</italic> abundance. In EBF, fecal pro-inflammatory cytokines (IL-1 beta, IL-8) were reduced. Strain-level metagenomic analysis allowed attributing the increased abundance of <italic>B. infantis</italic> in EGs versus CG, to LMG11588 probiotic colonization. Colonization by autochthonous <italic>B. infantis</italic> strains was similar between groups.</p></sec><sec id="sec4"><title>Discussion</title><p><italic>B. infantis</italic> LMG11588 supplementation was associated with normal infant growth, was safe and well-tolerated and promoted a <italic>Bifidobacterium</italic>-rich microbiota driven by <italic>B. infantis</italic> LMG11588 colonization without disturbing the natural dispersal of autochthonous <italic>B. infantis</italic> strains. In EBF, supplementation stimulated microbial metabolic activity and beneficially modulated enteric inflammation.</p></sec>