Effects of multistrain Bifidobacteria and Lactobacillus probiotics on HMO compositions after supplementation to pregnant women at threatening preterm delivery: design of the randomized clinical PROMO trial.

Bifidobacteria Entero-mammary pathway Human milk oligosaccharides Microbiome Preterm birth Probiotics

Journal

Molecular and cellular pediatrics
ISSN: 2194-7791
Titre abrégé: Mol Cell Pediatr
Pays: Germany
ID NLM: 101660689

Informations de publication

Date de publication:
01 Aug 2024
Historique:
received: 05 04 2024
accepted: 22 07 2024
medline: 1 8 2024
pubmed: 1 8 2024
entrez: 31 7 2024
Statut: epublish

Résumé

As an indigestible component of human breast milk, Human Milk Oligosaccharides (HMOs) play an important role as a substrate for the establishing microbiome of the newborn. They have further been shown to have beneficial effects on the immune system, lung and brain development. For preterm infants HMO composition of human breast milk may be of particular relevance since the establishment of a healthy microbiome is challenged by multiple disruptive factors associated with preterm birth, such as cesarean section, hospital environment and perinatal antibiotic exposure. In a previous study it has been proposed that maternal probiotic supplementation during late stages of pregnancy may change the HMO composition in human milk. However, there is currently no study on pregnancies which are threatened to preterm birth. Furthermore, HMO composition has not been investigated in association with clinically relevant outcomes of vulnerable infants including inflammation-mediated diseases such as sepsis, necrotizing enterocolitis (NEC) or chronic lung disease. A randomized controlled intervention study (PROMO = probiotics for human milk oligosaccharides) has been designed to analyze changes in HMO composition of human breast milk after supplementation of probiotics (Lactobacillus acidophilus, Bifidobacterium lactis and Bifidobacterium infantis) in pregnancies at risk for preterm birth. The primary endpoint is HMO composition of 3-fucosyllactose and 3'-sialyllactose in expressed breast milk. We estimate that probiotic intervention will increase these two HMO levels by 50% according to the standardized mean difference between treatment and control groups. As secondary outcomes we will measure preterm infants' clinical outcomes (preterm birth, sepsis, weight gain growth, gastrointestinal complications) and effects on microbiome composition in the rectovaginal tract of mothers at delivery and in the gut of term and preterm infants by sequencing at high genomic resolution. Therefore, we will longitudinally collect bio samples in the first 4 weeks after birth as well as in follow-up investigations at 3 months, one year, and five years of age. We estimate that probiotic intervention will increase these two HMO levels by 50% according to the standardized mean difference between treatment and control groups. The PROMO study will gain insight into the microbiome-HMO interaction at the fetomaternal interface and its consequences for duration of pregnancy and outcome of infants.

Sections du résumé

BACKGROUND BACKGROUND
As an indigestible component of human breast milk, Human Milk Oligosaccharides (HMOs) play an important role as a substrate for the establishing microbiome of the newborn. They have further been shown to have beneficial effects on the immune system, lung and brain development. For preterm infants HMO composition of human breast milk may be of particular relevance since the establishment of a healthy microbiome is challenged by multiple disruptive factors associated with preterm birth, such as cesarean section, hospital environment and perinatal antibiotic exposure. In a previous study it has been proposed that maternal probiotic supplementation during late stages of pregnancy may change the HMO composition in human milk. However, there is currently no study on pregnancies which are threatened to preterm birth. Furthermore, HMO composition has not been investigated in association with clinically relevant outcomes of vulnerable infants including inflammation-mediated diseases such as sepsis, necrotizing enterocolitis (NEC) or chronic lung disease.
MAIN BODY METHODS
A randomized controlled intervention study (PROMO = probiotics for human milk oligosaccharides) has been designed to analyze changes in HMO composition of human breast milk after supplementation of probiotics (Lactobacillus acidophilus, Bifidobacterium lactis and Bifidobacterium infantis) in pregnancies at risk for preterm birth. The primary endpoint is HMO composition of 3-fucosyllactose and 3'-sialyllactose in expressed breast milk. We estimate that probiotic intervention will increase these two HMO levels by 50% according to the standardized mean difference between treatment and control groups. As secondary outcomes we will measure preterm infants' clinical outcomes (preterm birth, sepsis, weight gain growth, gastrointestinal complications) and effects on microbiome composition in the rectovaginal tract of mothers at delivery and in the gut of term and preterm infants by sequencing at high genomic resolution. Therefore, we will longitudinally collect bio samples in the first 4 weeks after birth as well as in follow-up investigations at 3 months, one year, and five years of age.
CONCLUSIONS CONCLUSIONS
We estimate that probiotic intervention will increase these two HMO levels by 50% according to the standardized mean difference between treatment and control groups. The PROMO study will gain insight into the microbiome-HMO interaction at the fetomaternal interface and its consequences for duration of pregnancy and outcome of infants.

Identifiants

pubmed: 39085734
doi: 10.1186/s40348-024-00179-5
pii: 10.1186/s40348-024-00179-5
doi:

Types de publication

Journal Article Review

Langues

eng

Pagination

6

Informations de copyright

© 2024. The Author(s).

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Auteurs

A Welp (A)

Department of Gynecology and Obstetrics, University Hospital of Lübeck, Lübeck, Germany. amrei.welp@uksh.de.

E Laser (E)

Department of Pediatrics, University Hospital of Lübeck, Lübeck, Germany.

K Seeger (K)

Institute of Chemistry and Metabolomics, University of Lübeck, Lübeck, Germany.

A Haiß (A)

Department of Pediatrics, University Hospital of Lübeck, Lübeck, Germany.

K Hanke (K)

Department of Pediatrics, University Hospital of Lübeck, Lübeck, Germany.

K Faust (K)

Department of Pediatrics, University Hospital of Lübeck, Lübeck, Germany.

G Stichtenoth (G)

Department of Pediatrics, University Hospital of Lübeck, Lübeck, Germany.

C Fortmann-Grote (C)

Department of Microbial Population Biology, Max Planck Institute for Evolutionary Biology, Plön, Germany.

J Pagel (J)

Department of Pediatrics, University Hospital of Hamburg-Eppendorf, Hamburg, Germany.
German Center for Infection Research, Lübeck, Germany.

J Rupp (J)

German Center for Infection Research, Lübeck, Germany.
Institute for Infectious Diseases and Microbiology, University of Lübeck, Lübeck, Germany.

W Göpel (W)

Department of Pediatrics, University Hospital of Lübeck, Lübeck, Germany.

M Gembicki (M)

Department of Gynecology and Obstetrics, University Hospital of Lübeck, Lübeck, Germany.

J L Scharf (JL)

Department of Gynecology and Obstetrics, University Hospital of Lübeck, Lübeck, Germany.

A Rody (A)

Department of Gynecology and Obstetrics, University Hospital of Lübeck, Lübeck, Germany.

E Herting (E)

Department of Pediatrics, University Hospital of Lübeck, Lübeck, Germany.

C Härtel (C)

Department of Pediatrics, University of Würzburg, Würzburg, Germany.

I Fortmann (I)

Department of Pediatrics, University Hospital of Lübeck, Lübeck, Germany.
German Center for Infection Research, Lübeck, Germany.

Classifications MeSH