Frontiers in Nutrition (Jul 2022)

Infant Formula With a Specific Blend of Five Human Milk Oligosaccharides Drives the Gut Microbiota Development and Improves Gut Maturation Markers: A Randomized Controlled Trial

  • Miroslava Bosheva,
  • Istvan Tokodi,
  • Aleksander Krasnow,
  • Helle Krogh Pedersen,
  • Oksana Lukjancenko,
  • Aron C. Eklund,
  • Dominik Grathwohl,
  • Norbert Sprenger,
  • Bernard Berger,
  • Colin I. Cercamondi,
  • 5 HMO Study Investigator Consortium,
  • Viktor Bauer,
  • Malgorzata Arciszewska,
  • Maria Tarneva,
  • Irina Popova,
  • Svilen Dosev,
  • Sirma Dimitrova,
  • Olga Nikolova,
  • Marzena Nowak,
  • Magdalena Szuflinska-Sidorowicz,
  • Bartosz Korczowski,
  • Rositsa Karcheva-Beloeva,
  • Stefan Banov,
  • Boguslawa Cimoszko,
  • Wieslaw Olechowski,
  • Robert Simko,
  • Zsuzsanna Tengelyi,
  • Piotr Korbal,
  • Marta Zolnowska,
  • Anton Bilev,
  • Georgios Vasilopoulos,
  • Sylwia Korzynska,
  • István Laki,
  • Margarita Koleva-Syarova,
  • Toni Grigorov,
  • Steliyana Kraeva,
  • Éva Kovács,
  • Rada Markova,
  • Grazyna Jasieniak-Pinis,
  • Katalin Fister,
  • Tatyana Stoeva

DOI
https://doi.org/10.3389/fnut.2022.920362
Journal volume & issue
Vol. 9

Abstract

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BackgroundHuman milk oligosaccharides (HMOs) have important biological functions for a healthy development in early life.ObjectiveThis study aimed to investigate gut maturation effects of an infant formula containing five HMOs (2′-fucosyllactose, 2′,3-di-fucosyllactose, lacto-N-tetraose, 3′-sialyllactose, and 6′-sialyllactose).MethodsIn a multicenter study, healthy infants (7–21 days old) were randomly assigned to a standard cow’s milk-based infant formula (control group, CG); the same formula with 1.5 g/L HMOs (test group 1, TG1); or with 2.5 g/L HMOs (test group 2, TG2). A human milk-fed group (HMG) was enrolled as a reference. Fecal samples collected at baseline (n∼150/formula group; HMG n = 60), age 3 (n∼140/formula group; HMG n = 65) and 6 (n∼115/formula group; HMG n = 60) months were analyzed for microbiome (shotgun metagenomics), metabolism, and biomarkers.ResultsAt both post-baseline visits, weighted UniFrac analysis indicated different microbiota compositions in the two test groups (TGs) compared to CG (P < 0.01) with coordinates closer to that of HMG. The relative abundance of Bifidobacterium longum subsp. infantis (B. infantis) was higher in TGs vs. CG (P < 0.05; except at 6 months: TG2 vs. CG P = 0.083). Bifidobacterium abundance was higher by ∼45% in TGs vs. CG at 6-month approaching HMG. At both post-baseline visits, toxigenic Clostridioides difficile abundance was 75–85% lower in TGs vs. CG (P < 0.05) and comparable with HMG. Fecal pH was significantly lower in TGs vs. CG, and the overall organic acid profile was different in TGs vs. CG, approaching HMG. At 3 months, TGs (vs. CG) had higher secretory immunoglobulin A (sIgA) and lower alpha-1-antitrypsin (P < 0.05). At 6 months, sIgA in TG2 vs. CG remained higher (P < 0.05), and calprotectin was lower in TG1 (P < 0.05) vs. CG.ConclusionInfant formula with a specific blend of five HMOs supports the development of the intestinal immune system and gut barrier function and shifts the gut microbiome closer to that of breastfed infants with higher bifidobacteria, particularly B. infantis, and lower toxigenic Clostridioides difficile.Clinical Trial Registration[https://clinicaltrials.gov/ct2/show/], identifier [NCT03722550].

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