Neonatal hypoxia leads to impaired intestinal function and changes in the composition and metabolism of its microbiota

Abstract Neonatal hypoxia, a prevalent complication during the perinatal period, poses a serious threat to the health of newborns. The intestine, as one of the most metabolically active organs under stress conditions, is particularly vulnerable and susceptible to hypoxic injury. Using a neonatal hyp...

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Main Authors: Jun Wen, Yue Wu, Fengfeng Zhang, Yanchu Wang, Aifen Yang, Wenwen Lu, Xiaofeng Zhao, Huaping Tao
Format: Article
Language:English
Published: Nature Portfolio 2025-05-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-00041-2
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author Jun Wen
Yue Wu
Fengfeng Zhang
Yanchu Wang
Aifen Yang
Wenwen Lu
Xiaofeng Zhao
Huaping Tao
author_facet Jun Wen
Yue Wu
Fengfeng Zhang
Yanchu Wang
Aifen Yang
Wenwen Lu
Xiaofeng Zhao
Huaping Tao
author_sort Jun Wen
collection DOAJ
description Abstract Neonatal hypoxia, a prevalent complication during the perinatal period, poses a serious threat to the health of newborns. The intestine, as one of the most metabolically active organs under stress conditions, is particularly vulnerable and susceptible to hypoxic injury. Using a neonatal hypoxic mouse model, we systematically investigated hypoxia-induced intestinal barrier damage and underlying mechanisms. Hypoxia caused significant structural abnormalities in the ileum and distal colon of neonatal mice, including increased numbers of F4/80+ cells (p = 0.0031), swollen mucus particles (p = 0.0119), and disrupted tight junction. At the genetic level, hypoxia caused dysregulation of the expression of genes involved in intestinal barrier function, including antimicrobial activity, immune response, intestinal motility, and nutrient absorption. Further 16 S rDNA sequencing revealed hypoxia-driven gut microbiota dysbiosis with general reduced microbial abundance and diversity (Chao1 = 0.1143, Shannon = 0.0571, and Simpson = 0.3429). Structural dysbiosis of the gut microbiota consequently perturbed metabolic homeostasis, especially enhancing the activity of glycolipid metabolism. Notably, results showed that hypoxia may interfere with neurotransmitter metabolism, thereby increasing the risk of neurological disorders.
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spelling doaj-art-df7026fe358c48b8aa03fe586c080a022025-08-20T01:47:33ZengNature PortfolioScientific Reports2045-23222025-05-0115111210.1038/s41598-025-00041-2Neonatal hypoxia leads to impaired intestinal function and changes in the composition and metabolism of its microbiotaJun Wen0Yue Wu1Fengfeng Zhang2Yanchu Wang3Aifen Yang4Wenwen Lu5Xiaofeng Zhao6Huaping Tao7Institute of Developmental and Regenerative Biology, Zhejiang Key Laboratory of Organ Development and Regeneration, College of Life and Environmental Sciences, Hangzhou Normal UniversityInstitute of Developmental and Regenerative Biology, Zhejiang Key Laboratory of Organ Development and Regeneration, College of Life and Environmental Sciences, Hangzhou Normal UniversityInstitute of Developmental and Regenerative Biology, Zhejiang Key Laboratory of Organ Development and Regeneration, College of Life and Environmental Sciences, Hangzhou Normal UniversityInstitute of Developmental and Regenerative Biology, Zhejiang Key Laboratory of Organ Development and Regeneration, College of Life and Environmental Sciences, Hangzhou Normal UniversityInstitute of Developmental and Regenerative Biology, Zhejiang Key Laboratory of Organ Development and Regeneration, College of Life and Environmental Sciences, Hangzhou Normal UniversityInstitute of Developmental and Regenerative Biology, Zhejiang Key Laboratory of Organ Development and Regeneration, College of Life and Environmental Sciences, Hangzhou Normal UniversityInstitute of Developmental and Regenerative Biology, Zhejiang Key Laboratory of Organ Development and Regeneration, College of Life and Environmental Sciences, Hangzhou Normal UniversityInstitute of Developmental and Regenerative Biology, Zhejiang Key Laboratory of Organ Development and Regeneration, College of Life and Environmental Sciences, Hangzhou Normal UniversityAbstract Neonatal hypoxia, a prevalent complication during the perinatal period, poses a serious threat to the health of newborns. The intestine, as one of the most metabolically active organs under stress conditions, is particularly vulnerable and susceptible to hypoxic injury. Using a neonatal hypoxic mouse model, we systematically investigated hypoxia-induced intestinal barrier damage and underlying mechanisms. Hypoxia caused significant structural abnormalities in the ileum and distal colon of neonatal mice, including increased numbers of F4/80+ cells (p = 0.0031), swollen mucus particles (p = 0.0119), and disrupted tight junction. At the genetic level, hypoxia caused dysregulation of the expression of genes involved in intestinal barrier function, including antimicrobial activity, immune response, intestinal motility, and nutrient absorption. Further 16 S rDNA sequencing revealed hypoxia-driven gut microbiota dysbiosis with general reduced microbial abundance and diversity (Chao1 = 0.1143, Shannon = 0.0571, and Simpson = 0.3429). Structural dysbiosis of the gut microbiota consequently perturbed metabolic homeostasis, especially enhancing the activity of glycolipid metabolism. Notably, results showed that hypoxia may interfere with neurotransmitter metabolism, thereby increasing the risk of neurological disorders.https://doi.org/10.1038/s41598-025-00041-2Neonatal hypoxiaIntestinal barrierGut microbiotaIntestinal dysfunctionMice
spellingShingle Jun Wen
Yue Wu
Fengfeng Zhang
Yanchu Wang
Aifen Yang
Wenwen Lu
Xiaofeng Zhao
Huaping Tao
Neonatal hypoxia leads to impaired intestinal function and changes in the composition and metabolism of its microbiota
Scientific Reports
Neonatal hypoxia
Intestinal barrier
Gut microbiota
Intestinal dysfunction
Mice
title Neonatal hypoxia leads to impaired intestinal function and changes in the composition and metabolism of its microbiota
title_full Neonatal hypoxia leads to impaired intestinal function and changes in the composition and metabolism of its microbiota
title_fullStr Neonatal hypoxia leads to impaired intestinal function and changes in the composition and metabolism of its microbiota
title_full_unstemmed Neonatal hypoxia leads to impaired intestinal function and changes in the composition and metabolism of its microbiota
title_short Neonatal hypoxia leads to impaired intestinal function and changes in the composition and metabolism of its microbiota
title_sort neonatal hypoxia leads to impaired intestinal function and changes in the composition and metabolism of its microbiota
topic Neonatal hypoxia
Intestinal barrier
Gut microbiota
Intestinal dysfunction
Mice
url https://doi.org/10.1038/s41598-025-00041-2
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