Changes in intestinal microflora and its metabolites underlie the cognitive impairment in preterm rats

BackgroundThe brain development of preterm infants is easily affected by various adverse extrauterine factors and complications, resulting in abnormal neurological and cognitive development. Recent studies have found that there is a significant correlation between intestinal microbial changes and co...

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Main Authors: Xiang Lu, Zhengyang Xue, Yu Qian, Shanjie Wei, Yu Qiao, Wen Zhang, Hongyan Lu
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-08-01
Series:Frontiers in Cellular and Infection Microbiology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fcimb.2022.945851/full
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author Xiang Lu
Xiang Lu
Zhengyang Xue
Yu Qian
Shanjie Wei
Yu Qiao
Wen Zhang
Wen Zhang
Hongyan Lu
author_facet Xiang Lu
Xiang Lu
Zhengyang Xue
Yu Qian
Shanjie Wei
Yu Qiao
Wen Zhang
Wen Zhang
Hongyan Lu
author_sort Xiang Lu
collection DOAJ
description BackgroundThe brain development of preterm infants is easily affected by various adverse extrauterine factors and complications, resulting in abnormal neurological and cognitive development. Recent studies have found that there is a significant correlation between intestinal microbial changes and cognitive behavior. Nevertheless, the correlation between the cognitive impairment and abnormal changes of intestinal microflora in the preterm newborn has been rarely elucidated.AimTo analyze the differences of fecal intestinal flora, short chain fatty acids (SCFAs) and microbiota-gut-brain axis (MGBA)-related serum factors between preterm birth with and without cognitive impairment.MethodsHealthy female rats (body weight 410 ± 40 g) of 16-17 days of gestation were selected for the establishment of preterm cognitive impairment model and screened by Morris water maze navigation experiments. The pathological change of rat hippocampus was confirmed by HE staining. The abundance of fecal intestinal microflora was determined by 16sRNA sequencing, while the contents of fecal SCFAs were examined by gas chromatography.ResultsCompared with the control group, the cognitive impairment group had decreased abundance and diversity of intestinal microflora and increased abundance of Proteobacteria at the level of phylum. While the abundances of Alistipes, Bacteroides, Prevotella, and Lactobacillus decreased significantly at the level of order, family, and genus, the abundances of Staphylococcaceae, Enterococci, Psychrobacter, and Oligella increased significantly. Moreover, the levels of total SCFAs and acetic acid in the disease group were significantly lower. The fecal abundance of acetic acid was positively correlated with that of Lactobacillaceae or Peptostreptococcaceae, and negatively correlated with that of Aerococcaceae, and Alcaligenaceae in disease rats. Furthermore, cognitive impairment caused significantly decreased levels of 5-HT, GABA, and BDNF, and increased levels of GR, CRH, IL-6, and TNF-α in rat blood.ConclusionAlterations in intestinal microflora structure and the abundances of SCFAs contributed substantially to the cognitive impairment in preterm rats, which was associated with significant changes in MGBA-related soluble factors.
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spelling doaj.art-960d2014eda84b71ad08542f1ac92bab2022-12-22T03:06:54ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882022-08-011210.3389/fcimb.2022.945851945851Changes in intestinal microflora and its metabolites underlie the cognitive impairment in preterm ratsXiang Lu0Xiang Lu1Zhengyang Xue2Yu Qian3Shanjie Wei4Yu Qiao5Wen Zhang6Wen Zhang7Hongyan Lu8Pediatrics, Affiliated Hospital of Jiangsu University, Zhenjiang, ChinaSchool of Medicine, Jiangsu University, Zhenjiang, ChinaPediatrics, Affiliated Hospital of Jiangsu University, Zhenjiang, ChinaSchool of Medicine, Jiangsu University, Zhenjiang, ChinaPediatrics, Affiliated Hospital of Jiangsu University, Zhenjiang, ChinaPediatrics, Affiliated Hospital of Jiangsu University, Zhenjiang, ChinaPediatrics, Affiliated Hospital of Jiangsu University, Zhenjiang, ChinaSchool of Medicine, Jiangsu University, Zhenjiang, ChinaPediatrics, Affiliated Hospital of Jiangsu University, Zhenjiang, ChinaBackgroundThe brain development of preterm infants is easily affected by various adverse extrauterine factors and complications, resulting in abnormal neurological and cognitive development. Recent studies have found that there is a significant correlation between intestinal microbial changes and cognitive behavior. Nevertheless, the correlation between the cognitive impairment and abnormal changes of intestinal microflora in the preterm newborn has been rarely elucidated.AimTo analyze the differences of fecal intestinal flora, short chain fatty acids (SCFAs) and microbiota-gut-brain axis (MGBA)-related serum factors between preterm birth with and without cognitive impairment.MethodsHealthy female rats (body weight 410 ± 40 g) of 16-17 days of gestation were selected for the establishment of preterm cognitive impairment model and screened by Morris water maze navigation experiments. The pathological change of rat hippocampus was confirmed by HE staining. The abundance of fecal intestinal microflora was determined by 16sRNA sequencing, while the contents of fecal SCFAs were examined by gas chromatography.ResultsCompared with the control group, the cognitive impairment group had decreased abundance and diversity of intestinal microflora and increased abundance of Proteobacteria at the level of phylum. While the abundances of Alistipes, Bacteroides, Prevotella, and Lactobacillus decreased significantly at the level of order, family, and genus, the abundances of Staphylococcaceae, Enterococci, Psychrobacter, and Oligella increased significantly. Moreover, the levels of total SCFAs and acetic acid in the disease group were significantly lower. The fecal abundance of acetic acid was positively correlated with that of Lactobacillaceae or Peptostreptococcaceae, and negatively correlated with that of Aerococcaceae, and Alcaligenaceae in disease rats. Furthermore, cognitive impairment caused significantly decreased levels of 5-HT, GABA, and BDNF, and increased levels of GR, CRH, IL-6, and TNF-α in rat blood.ConclusionAlterations in intestinal microflora structure and the abundances of SCFAs contributed substantially to the cognitive impairment in preterm rats, which was associated with significant changes in MGBA-related soluble factors.https://www.frontiersin.org/articles/10.3389/fcimb.2022.945851/fullpreterm deliverycognitive impairmentintestinal microflorashort-chain fatty acidsmicrobiota-gut-brain axisabundance
spellingShingle Xiang Lu
Xiang Lu
Zhengyang Xue
Yu Qian
Shanjie Wei
Yu Qiao
Wen Zhang
Wen Zhang
Hongyan Lu
Changes in intestinal microflora and its metabolites underlie the cognitive impairment in preterm rats
Frontiers in Cellular and Infection Microbiology
preterm delivery
cognitive impairment
intestinal microflora
short-chain fatty acids
microbiota-gut-brain axis
abundance
title Changes in intestinal microflora and its metabolites underlie the cognitive impairment in preterm rats
title_full Changes in intestinal microflora and its metabolites underlie the cognitive impairment in preterm rats
title_fullStr Changes in intestinal microflora and its metabolites underlie the cognitive impairment in preterm rats
title_full_unstemmed Changes in intestinal microflora and its metabolites underlie the cognitive impairment in preterm rats
title_short Changes in intestinal microflora and its metabolites underlie the cognitive impairment in preterm rats
title_sort changes in intestinal microflora and its metabolites underlie the cognitive impairment in preterm rats
topic preterm delivery
cognitive impairment
intestinal microflora
short-chain fatty acids
microbiota-gut-brain axis
abundance
url https://www.frontiersin.org/articles/10.3389/fcimb.2022.945851/full
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