Human milk oligosaccharides reduce necrotizing enterocolitis-induced neuroinflammation and cognitive impairment in mice.

Autor:	Sodhi CP; Division of General Pediatric Surgery, Johns Hopkins University and Johns Hopkins Children's Center, Baltimore, Maryland, United States.; Department of Surgery, Johns Hopkins University and Johns Hopkins Children's Center, Baltimore, Maryland, United States., Ahmad R; Division of General Pediatric Surgery, Johns Hopkins University and Johns Hopkins Children's Center, Baltimore, Maryland, United States.; Department of Surgery, Johns Hopkins University and Johns Hopkins Children's Center, Baltimore, Maryland, United States., Fulton WB; Division of General Pediatric Surgery, Johns Hopkins University and Johns Hopkins Children's Center, Baltimore, Maryland, United States.; Department of Surgery, Johns Hopkins University and Johns Hopkins Children's Center, Baltimore, Maryland, United States., Lopez CM; Division of General Pediatric Surgery, Johns Hopkins University and Johns Hopkins Children's Center, Baltimore, Maryland, United States.; Department of Surgery, Johns Hopkins University and Johns Hopkins Children's Center, Baltimore, Maryland, United States., Eke BO; Division of General Pediatric Surgery, Johns Hopkins University and Johns Hopkins Children's Center, Baltimore, Maryland, United States.; Department of Surgery, Johns Hopkins University and Johns Hopkins Children's Center, Baltimore, Maryland, United States., Scheese D; Division of General Pediatric Surgery, Johns Hopkins University and Johns Hopkins Children's Center, Baltimore, Maryland, United States.; Department of Surgery, Johns Hopkins University and Johns Hopkins Children's Center, Baltimore, Maryland, United States., Duess JW; Division of General Pediatric Surgery, Johns Hopkins University and Johns Hopkins Children's Center, Baltimore, Maryland, United States.; Department of Surgery, Johns Hopkins University and Johns Hopkins Children's Center, Baltimore, Maryland, United States., Steinway SN; Division of General Pediatric Surgery, Johns Hopkins University and Johns Hopkins Children's Center, Baltimore, Maryland, United States.; Department of Surgery, Johns Hopkins University and Johns Hopkins Children's Center, Baltimore, Maryland, United States., Raouf Z; Division of General Pediatric Surgery, Johns Hopkins University and Johns Hopkins Children's Center, Baltimore, Maryland, United States.; Department of Surgery, Johns Hopkins University and Johns Hopkins Children's Center, Baltimore, Maryland, United States., Moore H; Division of General Pediatric Surgery, Johns Hopkins University and Johns Hopkins Children's Center, Baltimore, Maryland, United States.; Department of Surgery, Johns Hopkins University and Johns Hopkins Children's Center, Baltimore, Maryland, United States., Tsuboi K; Division of General Pediatric Surgery, Johns Hopkins University and Johns Hopkins Children's Center, Baltimore, Maryland, United States.; Department of Surgery, Johns Hopkins University and Johns Hopkins Children's Center, Baltimore, Maryland, United States., Sampah ME; Division of General Pediatric Surgery, Johns Hopkins University and Johns Hopkins Children's Center, Baltimore, Maryland, United States.; Department of Surgery, Johns Hopkins University and Johns Hopkins Children's Center, Baltimore, Maryland, United States., Jang HS; Division of General Pediatric Surgery, Johns Hopkins University and Johns Hopkins Children's Center, Baltimore, Maryland, United States.; Department of Surgery, Johns Hopkins University and Johns Hopkins Children's Center, Baltimore, Maryland, United States., Buck RH; Nutrition Division, Abbott, Columbus, Ohio, United States., Hill DR; Nutrition Division, Abbott, Columbus, Ohio, United States., Niemiro GM; Nutrition Division, Abbott, Columbus, Ohio, United States., Prindle T Jr; Division of General Pediatric Surgery, Johns Hopkins University and Johns Hopkins Children's Center, Baltimore, Maryland, United States.; Department of Surgery, Johns Hopkins University and Johns Hopkins Children's Center, Baltimore, Maryland, United States., Wang S; Division of General Pediatric Surgery, Johns Hopkins University and Johns Hopkins Children's Center, Baltimore, Maryland, United States.; Department of Surgery, Johns Hopkins University and Johns Hopkins Children's Center, Baltimore, Maryland, United States., Wang M; Division of General Pediatric Surgery, Johns Hopkins University and Johns Hopkins Children's Center, Baltimore, Maryland, United States.; Department of Surgery, Johns Hopkins University and Johns Hopkins Children's Center, Baltimore, Maryland, United States., Jia H; Division of General Pediatric Surgery, Johns Hopkins University and Johns Hopkins Children's Center, Baltimore, Maryland, United States.; Department of Surgery, Johns Hopkins University and Johns Hopkins Children's Center, Baltimore, Maryland, United States., Catazaro J; Department of Chemistry, Johns Hopkins University, Baltimore, Maryland, United States., Lu P; Division of General Pediatric Surgery, Johns Hopkins University and Johns Hopkins Children's Center, Baltimore, Maryland, United States.; Department of Surgery, Johns Hopkins University and Johns Hopkins Children's Center, Baltimore, Maryland, United States., Hackam DJ; Division of General Pediatric Surgery, Johns Hopkins University and Johns Hopkins Children's Center, Baltimore, Maryland, United States.; Department of Surgery, Johns Hopkins University and Johns Hopkins Children's Center, Baltimore, Maryland, United States.
Jazyk:	angličtina
Zdroj:	American journal of physiology. Gastrointestinal and liver physiology [Am J Physiol Gastrointest Liver Physiol] 2023 Jul 01; Vol. 325 (1), pp. G23-G41. Date of Electronic Publication: 2023 Apr 25.
DOI:	10.1152/ajpgi.00233.2022
Abstrakt:	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) 2'-fucosyllactose (2'-FL) and 6'-sialyslactose (6'-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 2'-FL or 6'-SL significantly attenuated NEC-induced 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, 2'-FL or 6'-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 2'-FL were detected in the infant mouse brain by nuclear magnetic resonance (NMR), whereas intact 2'-FL was not. Strikingly, the beneficial effects of 2'-FL or 6'-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 2'-FL and 6'-SL interrupt the gut-brain inflammatory axis and reduce the risk of NEC-induced brain injury. NEW & NOTEWORTHY This study reveals that the administration of human milk oligosaccharides, which are present in human breast milk, can interfere with the proinflammatory gut-brain axis and prevent neuroinflammation in the setting of necrotizing enterocolitis, a major intestinal disorder seen in premature infants.
Databáze:	MEDLINE
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