Human milk nutrient fortifiers alter the developing gastrointestinal microbiota of very-low-birth-weight infants

Michelle R Asbury; Sara Shama; Jong Yup Sa; Nicole Bando; James Butcher; Elena M Comelli; Julia K Copeland; Victoria Forte; Alex Kiss; Philip M Sherman; Alain Stintzi; Amel Taibi; Christopher Tomlinson; Sharon Unger; Pauline W Wang; Deborah L O'Connor; OptiMoM Feeding Group

doi:10.1016/j.chom.2022.07.011

Human milk nutrient fortifiers alter the developing gastrointestinal microbiota of very-low-birth-weight infants

Cell Host Microbe. 2022 Sep 14;30(9):1328-1339.e5. doi: 10.1016/j.chom.2022.07.011. Epub 2022 Aug 19.

Authors

Michelle R Asbury¹, Sara Shama¹, Jong Yup Sa¹, Nicole Bando¹, James Butcher², Elena M Comelli³, Julia K Copeland⁴, Victoria Forte¹, Alex Kiss⁵, Philip M Sherman⁶, Alain Stintzi², Amel Taibi⁷, Christopher Tomlinson⁸, Sharon Unger⁹, Pauline W Wang⁴, Deborah L O'Connor¹⁰; OptiMoM Feeding Group

Affiliations

¹ Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada; Translational Medicine Program, SickKids Research Institute, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.
² Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON K1N 6N5, Canada; Ottawa Institute of Systems Biology, University of Ottawa, Ottawa ON, K1H 8M5, Canada.
³ Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada; Joannah and Brian Lawson Centre for Child Nutrition, University of Toronto, Toronto, ON M5S 1A8, Canada.
⁴ Centre for the Analysis of Genome Evolution and Function, University of Toronto, Toronto, ON M5S 3B2, Canada.
⁵ Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON M5T 3M6, Canada; Evaluative and Clinical Sciences, Sunnybrook Research Institute, Toronto, ON M4N 3M5, Canada.
⁶ Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada; Cell Biology Program, SickKids Research Institute, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Gastroenterology, Hepatology, and Nutrition, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A8, Canada; Faculty of Dentistry, University of Toronto, Toronto, ON M5G 1X3, Canada.
⁷ Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada.
⁸ Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada; Translational Medicine Program, SickKids Research Institute, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Joannah and Brian Lawson Centre for Child Nutrition, University of Toronto, Toronto, ON M5S 1A8, Canada; Department of Pediatrics, University of Toronto, Toronto, ON M5G 1X8, Canada; Division of Neonatology, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada.
⁹ Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada; Department of Pediatrics, University of Toronto, Toronto, ON M5G 1X8, Canada; Division of Neonatology, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada; Department of Pediatrics, Sinai Health, Toronto, ON M5G 1X5, Canada; Rogers Hixon Ontario Human Milk Bank, Toronto, ON M5G 1X5, Canada.
¹⁰ Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada; Translational Medicine Program, SickKids Research Institute, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Joannah and Brian Lawson Centre for Child Nutrition, University of Toronto, Toronto, ON M5S 1A8, Canada; Department of Pediatrics, Sinai Health, Toronto, ON M5G 1X5, Canada; Rogers Hixon Ontario Human Milk Bank, Toronto, ON M5G 1X5, Canada. Electronic address: [email protected].

PMID: 35987195
DOI: 10.1016/j.chom.2022.07.011

Abstract

Nutrient fortifiers are added to human milk to support the development of very-low-birth-weight infants. Currently, bovine-milk-based fortifiers (BMBFs) are predominantly administered, with increasing interest in adopting human-milk-based fortifiers (HMBFs). Although beneficial for growth, their effects on the gastrointestinal microbiota are unclear. This triple-blind, randomized clinical trial (NCT02137473) tested how nutrient-enriching human milk with HMBF versus BMBF affects the gastrointestinal microbiota of infants born < 1,250 g during hospitalization. HMBF-fed infants (n = 63, n = 269 stools) showed lower microbial diversity, altered microbial community structure, and changes in predicted microbial functions compared with BMBF-fed infants (n = 56, n = 239 stools). HMBF-fed infants had higher relative and normalized abundances of unclassified Enterobacteriaceae and lower abundances of Clostridium sensu stricto. Post hoc analyses identified dose-dependent relationships between individual feed components (volumes of mother's milk, donor milk, and fortifiers) and the microbiota. These results highlight how nutrient fortifiers impact the microbiota of very-low-birth-weight infants during a critical developmental window.

Keywords: bovine-milk-based fortifier; donor milk; human milk; human-milk-based fortifier; microbiome; microbiota; mother’s milk; nutrient fortification; preterm infant; very-low-birth-weight infant.

Publication types

Randomized Controlled Trial

MeSH terms

Animals
Cattle
Food, Fortified
Gastrointestinal Microbiome*
Humans
Infant
Infant, Newborn
Infant, Premature
Infant, Very Low Birth Weight
Milk, Human*
Nutrients

Associated data

ClinicalTrials.gov/NCT02137473