Human milk oligosaccharides promote intestinal epithelium regeneration independent of the microbiota during necrotizing enterocolitis

Andrea Zito^{1

2}, Richard Y Wu^{3

4}, Bo Li^{1

2}, Steven R Botts^{3

4}, Mehrsa Feizi^{1

2}, Dorothy Lee^{1

2}, Carol Lee^{1

2}, Kathene C Johnson-Henry^{3

4}, Michael G Surette^{5

6}, Philip M Sherman^{3

4

7

8}, Agostino Pierro^{9

10

11

12

13}

Affiliations

¹ Translational Medicine Program, The Hospital for Sick Children, Toronto, ON, M5G 1X8, Canada.
² Division of General and Thoracic Surgery, The Hospital for Sick Children, Toronto, ON, M5G 1X8, Canada.
³ Cell Biology Program, The Hospital for Sick Children, Toronto, ON, M5G 1X8, Canada.
⁴ Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, Toronto, ON, M5G 1X8, Canada.
⁵ Department of Medicine, Faculty of Health Sciences, McMaster University, Hamilton, ON, L8S 4L8, Canada.
⁶ Department of Biochemistry and Biomedical Sciences, Faculty of Health Sciences, McMaster University, Hamilton, ON, L8S 4L8, Canada.
⁷ Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto, Toronto, ON, M5S 1A8, Canada.
⁸ Faculty of Dentistry, University of Toronto, Toronto, ON, M5G 1G6, Canada.
⁹ Translational Medicine Program, The Hospital for Sick Children, Toronto, ON, M5G 1X8, Canada. agostino.pierro@sickkids.ca.
¹⁰ Division of General and Thoracic Surgery, The Hospital for Sick Children, Toronto, ON, M5G 1X8, Canada. agostino.pierro@sickkids.ca.
¹¹ Department of Surgery, University of Toronto, Toronto, ON, M5S 1A8, Canada. agostino.pierro@sickkids.ca.
¹² Institute of Medical Science, University of Toronto, Toronto, ON, M5S 1A8, Canada. agostino.pierro@sickkids.ca.
¹³ Department of Physiology, University of Toronto, Toronto, ON, M5S 1A8, Canada. agostino.pierro@sickkids.ca.

PMID: 38216767
DOI: 10.1007/s00383-023-05598-5

Human milk oligosaccharides promote intestinal epithelium regeneration independent of the microbiota during necrotizing enterocolitis

Andrea Zito et al. Pediatr Surg Int. 2024.

. 2024 Jan 12;40(1):35.

doi: 10.1007/s00383-023-05598-5.

Authors

Affiliations

¹ Translational Medicine Program, The Hospital for Sick Children, Toronto, ON, M5G 1X8, Canada.
² Division of General and Thoracic Surgery, The Hospital for Sick Children, Toronto, ON, M5G 1X8, Canada.
³ Cell Biology Program, The Hospital for Sick Children, Toronto, ON, M5G 1X8, Canada.
⁴ Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, Toronto, ON, M5G 1X8, Canada.
⁵ Department of Medicine, Faculty of Health Sciences, McMaster University, Hamilton, ON, L8S 4L8, Canada.
⁶ Department of Biochemistry and Biomedical Sciences, Faculty of Health Sciences, McMaster University, Hamilton, ON, L8S 4L8, Canada.
⁷ Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto, Toronto, ON, M5S 1A8, Canada.
⁸ Faculty of Dentistry, University of Toronto, Toronto, ON, M5G 1G6, Canada.
⁹ Translational Medicine Program, The Hospital for Sick Children, Toronto, ON, M5G 1X8, Canada. agostino.pierro@sickkids.ca.
¹⁰ Division of General and Thoracic Surgery, The Hospital for Sick Children, Toronto, ON, M5G 1X8, Canada. agostino.pierro@sickkids.ca.
¹¹ Department of Surgery, University of Toronto, Toronto, ON, M5S 1A8, Canada. agostino.pierro@sickkids.ca.
¹² Institute of Medical Science, University of Toronto, Toronto, ON, M5S 1A8, Canada. agostino.pierro@sickkids.ca.
¹³ Department of Physiology, University of Toronto, Toronto, ON, M5S 1A8, Canada. agostino.pierro@sickkids.ca.

PMID: 38216767
DOI: 10.1007/s00383-023-05598-5

Abstract

Purpose: Necrotizing enterocolitis (NEC) is a severe intestinal disease primarily affecting premature infants, marked by impaired epithelial regeneration. Breastfed infants are less susceptible to NEC than formula-fed ones, and human milk oligosaccharides (HMO) found in breast milk have prebiotic properties that can protect against NEC. However, it is unclear how HMOs influence intestinal epithelium regeneration in relation to the gut microbiota.

Methods: Broad-spectrum antibiotics were administered to pregnant dams to reduce the microbiota in offspring. NEC was induced through administration of hyperosmolar formula, lipopolysaccharide, and hypoxia from postnatal days (p) 5-9. Intestinal epithelial organoids were derived from p9 mice. HMOs were isolated from human donor breast milk and then solubilized in the formula for each feed or culture media for organoids.

Results: HMOs did not alter the microbiota profile in the presence of a normal or reduced microbiota. In the reduced microbiota, HMO treatment decreased NEC intestinal injury, and increased proliferation and stem cell activity. Additionally, in the complete absence of the microbiota, HMOs stimulated intestinal organoid growth.

Conclusion: This study demonstrates that HMOs promoted intestinal epithelial regeneration independent of the gut microbiota. These findings provide further insight into the various benefits HMOs may have in the protection against NEC.

Keywords: Human milk oligosaccharides; Intestinal epithelial regeneration; Microbiota; Necrotizing enterocolitis.

PubMed Disclaimer

References

1. Luig M, Lui K, NSW & ACT NICUS Group (2005) Epidemiology of necrotizing enterocolitis – Part II: Risks and susceptibility of premature infants during the surfactant era: A regional study. J Paediatr Child Health 41:174–179. https://doi.org/10.1111/j.1440-1754.2005.00583.x - DOI - PubMed
1. Fitzgibbons SC, Ching Y, Yu D, Carpenter J, Kenny M, Weldon C et al (2009) Mortality of necrotizing enterocolitis expressed by birth weight categories. J Pediatr Surg 44:1072–1076. https://doi.org/10.1016/j.jpedsurg.2009.02.013 - DOI - PubMed
1. Barker N (2014) Adult intestinal stem cells: critical drivers of epithelial homeostasis and regeneration. Nat Rev Mol Cell Biol 15:19–33. https://doi.org/10.1038/nrm3721 - DOI - PubMed
1. Denning N-L, Prince JM (2018) Neonatal intestinal dysbiosis in necrotizing enterocolitis. Mol Med 24:4. https://doi.org/10.1186/s10020-018-0002-0 - DOI - PubMed - PMC
1. Lucas A, Cole TJ (1990) Breast milk and neonatal necrotising enterocolitis. The Lancet 336:1519–1523. https://doi.org/10.1016/0140-6736(90)93304-8 - DOI

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Substances

Actions

Grants and funding

LinkOut - more resources

Full Text Sources
- Springer
Medical
- MedlinePlus Consumer Health Information
- MedlinePlus Health Information

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Human milk oligosaccharides promote intestinal epithelium regeneration independent of the microbiota during necrotizing enterocolitis

Affiliations

Human milk oligosaccharides promote intestinal epithelium regeneration independent of the microbiota during necrotizing enterocolitis

Authors

Affiliations

Abstract

References

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Medical