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Human milk cream alters intestinal microbiome of preterm infants: a prospective cohort study

Pediatric Research (2024)Cite this article

Abstract

Background

In very low birth weight (VLBW) infants, human milk cream added to standard human milk fortification is used to improve growth. This study aimed to evaluate the impact of cream supplement on the intestinal microbiome of VLBW infants.

Methods

Whole genome shotgun sequencing was performed on stool (n = 57) collected from a cohort of 23 infants weighing 500-1250 grams (control = 12, cream = 11). Both groups received an exclusive human milk diet (mother’s own milk, donor human milk, and donor human milk-derived fortifier) with the cream group receiving an additional 2 kcal/oz cream at 100 mL/kg/day of fortified feeds and then 4 kcal/oz if poor growth.

Results

While there were no significant differences in alpha diversity, infants receiving cream significantly differed from infants in the control group in beta diversity. Cream group samples had significantly higher prevalence of Proteobacteria and significantly lower Firmicutes compared to control group. Klebsiella species dominated the microbiota of cream-exposed infants, along with bacterial pathways involved in lipid metabolism and metabolism of cofactors and amino acids.

Conclusions

Cream supplementation significantly altered composition of the intestinal microbiome of VLBW infants to favor increased prevalence of Proteobacteria and functional gene content associated with these bacteria.

Impact

  • We report changes to the intestinal microbiome associated with administration of human milk cream; a novel supplement used to improve growth rates of preterm very low birth weight infants.

  • Since little is known about the impact of cream on intestinal microbiota composition of very low birth weight infants, our study provides valuable insight on the effects of diet on the microbiome of this population.

  • Dietary supplements administered to preterm infants in neonatal intensive care units have the potential to influence the intestinal microbiome composition which may affect overall health status of the infant.

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Fig. 1: Comparison of alpha-diversity of microbiota in preterm infants.
Fig. 2: Beta-diversity of microbiota in preterm infants.
Fig. 3: Effect of cream supplementation and weeks of life on intestinal microbiota composition in preterm infants.
Fig. 4: Effect of cream supplementation and weeks of life on intestinal microbiota functional profile in preterm infants.
Fig. 5: Venn diagram depicting functional pathways of the bacterial metagenome in VLBW infants.

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Data availability

The data is openly available in the National Center for Biotechnology Information BioSample database under Bioproject ID PRJNA1062322.

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Acknowledgements

We would like to thank the investigators from the Multicenter Human Milk Cream Study: Linda Cooper, MD, Jenelle Ferry, MD, Ursula Kiechl-Kohlendorfer, MD, MSc, Stephanie Attarian, MD, Barbara Warner, MD, Dale Gerstmann, MD, Padmani Karna, MD, Craig Anderson, MD, Vinayak Govande, MD, Boriana Parvez, MD, Andrea Willeitner, MD, Raja Nandyal, MD, Jose A. Perez, MD, David Riley, MD, Lewis P. Rubin, MD, Martin L. Lee, PhD, Cynthia L. Blanco, MD. Research reported in this publication was supported by the National Institute of General Medical Sciences of the National Institutes of Health under Award Number T32GM136554. A.B.H. is supported by the Maternal and Child Health Nutrition Training Grant T79 MC00023 and the National Institute of Health (NIH) grant R01 DK124614. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Prolacta Bioscience provided a research grant for the microbiome analysis in this study. Prolacta had no role in the execution of the experiments or interpretation of the results.

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Authors and Affiliations

  1. Graduate Program in Immunology & Microbiology, Baylor College of Medicine, Houston, TX, USA

    Grace O. Adeniyi-Ipadeola

  2. Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, USA

    Grace O. Adeniyi-Ipadeola, Sara J. Javornik Cregeen & Sasirekha Ramani

  3. The Alkek Center for Metagenomics and Microbiome Research, Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, USA

    Kristi L. Hoffman & Sara J. Javornik Cregeen

  4. Section of Neonatology, Department of Pediatrics, Baylor College of Medicine, Texas Children’s Hospital, Houston, TX, USA

    Heeju Yang & Amy B. Hair

  5. Division of Gastroenterology, Hepatology & Nutrition, Department of Pediatrics, Baylor College of Medicine and Texas Children’s Hospital, Houston, TX, USA

    Geoffrey A. Preidis

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  1. Grace O. Adeniyi-Ipadeola
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Contributions

Study design: A.B.H., S.R., G.O.A.-I., S.J.C., K.L.H. Data acquisition: H.Y., A.B.H. Data analysis: G.O.A.-I., K.L.H., S.J.C. Data interpretation: G.O.A.-I., K.L.H., S.J.C., S.R., G.A.P., A.B.H. Article drafts: G.O.A.-I., K.L.H., H.Y., S.J.C. Article revisions: G.O.A.-I., K.L.H., S.J.C., S.R., G.A.P., A.B.H.

Corresponding author

Correspondence to Amy B. Hair.

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The authors declare no competing interests.

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Verbal and written information was given to the infants’ parents or legal guardians, and they gave their written consent to participate before the infant was included in the study.

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Adeniyi-Ipadeola, G.O., Hoffman, K.L., Yang, H. et al. Human milk cream alters intestinal microbiome of preterm infants: a prospective cohort study. Pediatr Res (2024). https://doi.org/10.1038/s41390-023-02948-w

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