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Human milk oligosaccharides reduce necrotizing enterocolitis-induced neuroinflammation and cognitive impairment in mice.
- Source :
-
American Journal of Physiology: Gastrointestinal & Liver Physiology . Jul2023, Vol. 325 Issue 1, pG23-G41. 19p. - Publication Year :
- 2023
-
Abstract
- Necrotizing enterocolitis (NEC) is the leading cause of morbidity and mortality in premature infants. One of the most devastating complications of NEC is the development of NEC-induced brain injury, which manifests as impaired cognition that persists beyond infancy and which represents a proinflammatory activation of the gut-brain axis. Given that oral administration of the human milk oligosaccharides (HMOs) 20-fucosyllactose (20-FL) and 60-sialyslactose (60-SL) significantly reduced intestinal inflammation in mice, we hypothesized that oral administration of these HMOs would reduce NEC-induced brain injury and sought to determine the mechanisms involved. We now show that the administration of either 20-FL or 60-SL significantly attenuated NECinduced brain injury, reversed myelin loss in the corpus callosum and midbrain of newborn mice, and prevented the impaired cognition observed in mice with NEC-induced brain injury. In seeking to define the mechanisms involved, 20-FL or 60-SL administration resulted in a restoration of the blood-brain barrier in newborn mice and also had a direct anti-inflammatory effect on the brain as revealed through the study of brain organoids. Metabolites of 20-FL were detected in the infant mouse brain by nuclear magnetic resonance (NMR), whereas intact 20-FL was not. Strikingly, the beneficial effects of 20-FL or 60-SL against NEC-induced brain injury required the release of the neurotrophic factor brain-derived neurotrophic factor (BDNF), as mice lacking BDNF were not protected by these HMOs from the development of NEC-induced brain injury. Taken in aggregate, these findings reveal that the HMOs 20-FL and 60-SL interrupt the gut-brain inflammatory axis and reduce the risk of NEC-induced brain injury. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 01931857
- Volume :
- 325
- Issue :
- 1
- Database :
- Academic Search Index
- Journal :
- American Journal of Physiology: Gastrointestinal & Liver Physiology
- Publication Type :
- Academic Journal
- Accession number :
- 164293619
- Full Text :
- https://doi.org/10.1152/ajpgi.00233.2022