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Alterations in intestinal microbiota and metabolites in individuals with Down syndrome and their correlation with inflammation and behavior disorders in mice

The intestinal microbiota and fecal metabolome have been shown to play a vital role in human health, and can be affected by genetic and environmental factors. We found that individuals with Down syndrome (DS) had abnormal serum cytokine levels indicative of a pro-inflammatory environment. We investi...

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Autores principales: Cai, Shaoli, Lin, Jinxin, Li, Zhaolong, Liu, Songnian, Feng, Zhihua, Zhang, Yangfan, Zhang, Yanding, Huang, Jianzhong, Chen, Qi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9998045/
https://www.ncbi.nlm.nih.gov/pubmed/36910172
http://dx.doi.org/10.3389/fmicb.2023.1016872
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author Cai, Shaoli
Lin, Jinxin
Li, Zhaolong
Liu, Songnian
Feng, Zhihua
Zhang, Yangfan
Zhang, Yanding
Huang, Jianzhong
Chen, Qi
author_facet Cai, Shaoli
Lin, Jinxin
Li, Zhaolong
Liu, Songnian
Feng, Zhihua
Zhang, Yangfan
Zhang, Yanding
Huang, Jianzhong
Chen, Qi
author_sort Cai, Shaoli
collection PubMed
description The intestinal microbiota and fecal metabolome have been shown to play a vital role in human health, and can be affected by genetic and environmental factors. We found that individuals with Down syndrome (DS) had abnormal serum cytokine levels indicative of a pro-inflammatory environment. We investigated whether these individuals also had alterations in the intestinal microbiome. High-throughput sequencing of bacterial 16S rRNA gene in fecal samples from 17 individuals with DS and 23 non-DS volunteers revealed a significantly higher abundance of Prevotella, Escherichia/Shigella, Catenibacterium, and Allisonella in individuals with DS, which was positively associated with the levels of pro-inflammatory cytokines. GC-TOF-MS-based fecal metabolomics identified 35 biomarkers (21 up-regulated metabolites and 14 down-regulated metabolites) that were altered in the microbiome of individuals with DS. Metabolic pathway enrichment analyses of these biomarkers showed a characteristic pattern in DS that included changes in valine, leucine, and isoleucine biosynthesis and degradation; synthesis and degradation of ketone bodies; glyoxylate and dicarboxylate metabolism; tyrosine metabolism; lysine degradation; and the citrate cycle. Treatment of mice with fecal bacteria from individuals with DS or Prevotella copri significantly altered behaviors often seen in individuals with DS, such as depression-associated behavior and impairment of motor function. These studies suggest that changes in intestinal microbiota and the fecal metabolome are correlated with chronic inflammation and behavior disorders associated with DS.
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spelling pubmed-99980452023-03-10 Alterations in intestinal microbiota and metabolites in individuals with Down syndrome and their correlation with inflammation and behavior disorders in mice Cai, Shaoli Lin, Jinxin Li, Zhaolong Liu, Songnian Feng, Zhihua Zhang, Yangfan Zhang, Yanding Huang, Jianzhong Chen, Qi Front Microbiol Microbiology The intestinal microbiota and fecal metabolome have been shown to play a vital role in human health, and can be affected by genetic and environmental factors. We found that individuals with Down syndrome (DS) had abnormal serum cytokine levels indicative of a pro-inflammatory environment. We investigated whether these individuals also had alterations in the intestinal microbiome. High-throughput sequencing of bacterial 16S rRNA gene in fecal samples from 17 individuals with DS and 23 non-DS volunteers revealed a significantly higher abundance of Prevotella, Escherichia/Shigella, Catenibacterium, and Allisonella in individuals with DS, which was positively associated with the levels of pro-inflammatory cytokines. GC-TOF-MS-based fecal metabolomics identified 35 biomarkers (21 up-regulated metabolites and 14 down-regulated metabolites) that were altered in the microbiome of individuals with DS. Metabolic pathway enrichment analyses of these biomarkers showed a characteristic pattern in DS that included changes in valine, leucine, and isoleucine biosynthesis and degradation; synthesis and degradation of ketone bodies; glyoxylate and dicarboxylate metabolism; tyrosine metabolism; lysine degradation; and the citrate cycle. Treatment of mice with fecal bacteria from individuals with DS or Prevotella copri significantly altered behaviors often seen in individuals with DS, such as depression-associated behavior and impairment of motor function. These studies suggest that changes in intestinal microbiota and the fecal metabolome are correlated with chronic inflammation and behavior disorders associated with DS. Frontiers Media S.A. 2023-02-23 /pmc/articles/PMC9998045/ /pubmed/36910172 http://dx.doi.org/10.3389/fmicb.2023.1016872 Text en Copyright © 2023 Cai, Lin, Li, Liu, Feng, Zhang, Zhang, Huang and Chen. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Microbiology
Cai, Shaoli
Lin, Jinxin
Li, Zhaolong
Liu, Songnian
Feng, Zhihua
Zhang, Yangfan
Zhang, Yanding
Huang, Jianzhong
Chen, Qi
Alterations in intestinal microbiota and metabolites in individuals with Down syndrome and their correlation with inflammation and behavior disorders in mice
title Alterations in intestinal microbiota and metabolites in individuals with Down syndrome and their correlation with inflammation and behavior disorders in mice
title_full Alterations in intestinal microbiota and metabolites in individuals with Down syndrome and their correlation with inflammation and behavior disorders in mice
title_fullStr Alterations in intestinal microbiota and metabolites in individuals with Down syndrome and their correlation with inflammation and behavior disorders in mice
title_full_unstemmed Alterations in intestinal microbiota and metabolites in individuals with Down syndrome and their correlation with inflammation and behavior disorders in mice
title_short Alterations in intestinal microbiota and metabolites in individuals with Down syndrome and their correlation with inflammation and behavior disorders in mice
title_sort alterations in intestinal microbiota and metabolites in individuals with down syndrome and their correlation with inflammation and behavior disorders in mice
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9998045/
https://www.ncbi.nlm.nih.gov/pubmed/36910172
http://dx.doi.org/10.3389/fmicb.2023.1016872
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