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Mitochondrial dysfunction in the gastrointestinal mucosa of children with autism: A blinded case-control study

Gastrointestinal (GI) symptoms are prevalent in autism spectrum disorder (ASD) but the pathophysiology is poorly understood. Imbalances in the enteric microbiome have been associated with ASD and can cause GI dysfunction potentially through disruption of mitochondrial function as microbiome metaboli...

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Autores principales: Rose, Shannon, Bennuri, Sirish C., Murray, Katherine F., Buie, Timothy, Winter, Harland, Frye, Richard Eugene
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5640251/
https://www.ncbi.nlm.nih.gov/pubmed/29028817
http://dx.doi.org/10.1371/journal.pone.0186377
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author Rose, Shannon
Bennuri, Sirish C.
Murray, Katherine F.
Buie, Timothy
Winter, Harland
Frye, Richard Eugene
author_facet Rose, Shannon
Bennuri, Sirish C.
Murray, Katherine F.
Buie, Timothy
Winter, Harland
Frye, Richard Eugene
author_sort Rose, Shannon
collection PubMed
description Gastrointestinal (GI) symptoms are prevalent in autism spectrum disorder (ASD) but the pathophysiology is poorly understood. Imbalances in the enteric microbiome have been associated with ASD and can cause GI dysfunction potentially through disruption of mitochondrial function as microbiome metabolites modulate mitochondrial function and mitochondrial dysfunction is highly associated with GI symptoms. In this study, we compared mitochondrial function in rectal and cecum biopsies under the assumption that certain microbiome metabolites, such as butyrate and propionic acid, are more abundant in the cecum as compared to the rectum. Rectal and cecum mucosal biopsies were collected during elective diagnostic colonoscopy. Using a single-blind case-control design, complex I and IV and citrate synthase activities and complex I-V protein quantity from 10 children with ASD, 10 children with Crohn’s disease and 10 neurotypical children with nonspecific GI complaints were measured. The protein for all complexes, except complex II, in the cecum as compared to the rectum was significantly higher in ASD samples as compared to other groups. For both rectal and cecum biopsies, ASD samples demonstrated higher complex I activity, but not complex IV or citrate synthase activity, compared to other groups. Mitochondrial function in the gut mucosa from children with ASD was found to be significantly different than other groups who manifested similar GI symptomatology suggesting a unique pathophysiology for GI symptoms in children with ASD. Abnormalities localized to the cecum suggest a role for imbalances in the microbiome, potentially in the production of butyrate, in children with ASD.
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spelling pubmed-56402512017-10-30 Mitochondrial dysfunction in the gastrointestinal mucosa of children with autism: A blinded case-control study Rose, Shannon Bennuri, Sirish C. Murray, Katherine F. Buie, Timothy Winter, Harland Frye, Richard Eugene PLoS One Research Article Gastrointestinal (GI) symptoms are prevalent in autism spectrum disorder (ASD) but the pathophysiology is poorly understood. Imbalances in the enteric microbiome have been associated with ASD and can cause GI dysfunction potentially through disruption of mitochondrial function as microbiome metabolites modulate mitochondrial function and mitochondrial dysfunction is highly associated with GI symptoms. In this study, we compared mitochondrial function in rectal and cecum biopsies under the assumption that certain microbiome metabolites, such as butyrate and propionic acid, are more abundant in the cecum as compared to the rectum. Rectal and cecum mucosal biopsies were collected during elective diagnostic colonoscopy. Using a single-blind case-control design, complex I and IV and citrate synthase activities and complex I-V protein quantity from 10 children with ASD, 10 children with Crohn’s disease and 10 neurotypical children with nonspecific GI complaints were measured. The protein for all complexes, except complex II, in the cecum as compared to the rectum was significantly higher in ASD samples as compared to other groups. For both rectal and cecum biopsies, ASD samples demonstrated higher complex I activity, but not complex IV or citrate synthase activity, compared to other groups. Mitochondrial function in the gut mucosa from children with ASD was found to be significantly different than other groups who manifested similar GI symptomatology suggesting a unique pathophysiology for GI symptoms in children with ASD. Abnormalities localized to the cecum suggest a role for imbalances in the microbiome, potentially in the production of butyrate, in children with ASD. Public Library of Science 2017-10-13 /pmc/articles/PMC5640251/ /pubmed/29028817 http://dx.doi.org/10.1371/journal.pone.0186377 Text en © 2017 Rose et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Rose, Shannon
Bennuri, Sirish C.
Murray, Katherine F.
Buie, Timothy
Winter, Harland
Frye, Richard Eugene
Mitochondrial dysfunction in the gastrointestinal mucosa of children with autism: A blinded case-control study
title Mitochondrial dysfunction in the gastrointestinal mucosa of children with autism: A blinded case-control study
title_full Mitochondrial dysfunction in the gastrointestinal mucosa of children with autism: A blinded case-control study
title_fullStr Mitochondrial dysfunction in the gastrointestinal mucosa of children with autism: A blinded case-control study
title_full_unstemmed Mitochondrial dysfunction in the gastrointestinal mucosa of children with autism: A blinded case-control study
title_short Mitochondrial dysfunction in the gastrointestinal mucosa of children with autism: A blinded case-control study
title_sort mitochondrial dysfunction in the gastrointestinal mucosa of children with autism: a blinded case-control study
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5640251/
https://www.ncbi.nlm.nih.gov/pubmed/29028817
http://dx.doi.org/10.1371/journal.pone.0186377
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