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

Frontiers in Nutrition

Olga Nikolova¹  Irina Popova¹  Georgios Vasilopoulos¹  Viktor Bauer¹  Rositsa Karcheva-Beloeva¹  Stefan Banov¹  Marta Zolnowska¹  Sirma Dimitrova¹  Boguslawa Cimoszko¹  Rada Markova¹  Bartosz Korczowski¹  Marzena Nowak¹  Magdalena Szuflinska-Sidorowicz¹  Zsuzsanna Tengelyi¹  Robert Simko¹  Anton Bilev¹  Grazyna Jasieniak-Pinis¹  Sylwia Korzynska¹  Toni Grigorov¹  Steliyana Kraeva¹  5 HMO Study Investigator Consortium¹  Wieslaw Olechowski¹  Margarita Koleva-Syarova¹  István Laki¹  Piotr Korbal¹  Katalin Fister¹  Tatyana Stoeva¹  Maria Tarneva¹  Svilen Dosev¹  Éva Kovács¹  Malgorzata Arciszewska¹  Dominik Grathwohl²  Oksana Lukjancenko³  Helle Krogh Pedersen³  Aron C. Eklund³  Aleksander Krasnow⁴  Istvan Tokodi⁵  Norbert Sprenger⁶  Bernard Berger⁶  Colin I. Cercamondi⁷  Miroslava Bosheva⁸ 

[1] ;Biostatistics and Data, Nestlé Research, Lausanne, Switzerland;Clinical Microbiomics, Copenhagen, Denmark;Gdansk Health Center, Gdańsk, Poland;Infant and Children’s Department, St. George’s Hospital, Székesfehérvár, Hungary;Nestlé Institute of Health Sciences, Nestlé Research, Lausanne, Switzerland;Nestlé Product Technology Center – Nutrition, Société des Produits Nestlé S.A., Vevey, Switzerland;University Multiprofile Hospital for Active Treatment, St. George Medical University, Plovdiv, Bulgaria;

关键词: human milk oligosaccharides (HMOs);    infant formula;    gut microbiota;    bifidobacteria;    Bifidobacterium longum subsp. infantis (B. infantis);    Clostridioides (C.) difficile;   

DOI  :  10.3389/fnut.2022.920362

来源: DOAJ

【 摘 要 】

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].

【 授权许可】

Unknown