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

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

doi:10.3389/fnut.2023.1319873

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

Front Nutr. 2023 Dec 14:10:1319873. doi: 10.3389/fnut.2023.1319873. eCollection 2023.

Authors

Affiliations

¹ Asian Hospital and Medical Center, Muntinlupa City, Philippines.
² Biostatistics & Data, Nestlé Research, Lausanne, Switzerland.
³ Nestlé Institute of Health Sciences, Nestlé Research, Société des Produits Nestlé S.A., Lausanne, Switzerland.
⁴ Clinical Microbiomics, Copenhagen, Denmark.
⁵ Nestlé Product Technology Center - Nutrition, Société des Produits Nestlé S.A., Vevey, Switzerland.

Abstract

Introduction: Bifidobacterium longum subspecies infantis (B. infantis) may play a key role in infant gut development. This trial evaluated safety, tolerability, and efficacy of B. infantis 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; n = 77), or any of two B. infantis experimental groups (EGs): low (Lo-EG; 1*10⁸ CFU/day; n = 75) or high dose (Hi-EG; 1.8*10¹⁰ CFU/day; n = 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 B. infantis abundance. In EBF, fecal pro-inflammatory cytokines (IL-1 beta, IL-8) were reduced. Strain-level metagenomic analysis allowed attributing the increased abundance of B. infantis in EGs versus CG, to LMG11588 probiotic colonization. Colonization by autochthonous B. infantis strains was similar between groups.

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

Keywords: B. infantis LMG11588; Bifidobacterium-rich microbiota; autochthonous strains; infant growth; safety.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. Nestlé Nutrition, Société des Produits Nestlé S.A., Switzerland funded the study.