Gut Microbiota Profiling and Gut–Brain Crosstalk in Children Affected by Pediatric Acute-Onset Neuropsychiatric Syndrome and Pediatric Autoimmune Neuropsychiatric Disorders Associated With Streptococcal Infections

Pediatric acute-onset neuropsychiatric syndrome (PANS) and pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections syndrome (PANDAS) are conditions that impair brain normal neurologic function, resulting in the sudden onset of tics, obsessive-compulsive disorder, and...

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Main Authors: Andrea Quagliariello, Federica Del Chierico, Alessandra Russo, Sofia Reddel, Giulia Conte, Loris R. Lopetuso, Gianluca Ianiro, Bruno Dallapiccola, Francesco Cardona, Antonio Gasbarrini, Lorenza Putignani
Format: Article
Language:English
Published: Frontiers Media S.A. 2018-04-01
Series:Frontiers in Microbiology
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Online Access:http://journal.frontiersin.org/article/10.3389/fmicb.2018.00675/full
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author Andrea Quagliariello
Federica Del Chierico
Alessandra Russo
Sofia Reddel
Giulia Conte
Loris R. Lopetuso
Gianluca Ianiro
Bruno Dallapiccola
Francesco Cardona
Antonio Gasbarrini
Lorenza Putignani
Lorenza Putignani
author_facet Andrea Quagliariello
Federica Del Chierico
Alessandra Russo
Sofia Reddel
Giulia Conte
Loris R. Lopetuso
Gianluca Ianiro
Bruno Dallapiccola
Francesco Cardona
Antonio Gasbarrini
Lorenza Putignani
Lorenza Putignani
author_sort Andrea Quagliariello
collection DOAJ
description Pediatric acute-onset neuropsychiatric syndrome (PANS) and pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections syndrome (PANDAS) are conditions that impair brain normal neurologic function, resulting in the sudden onset of tics, obsessive-compulsive disorder, and other behavioral symptoms. Recent studies have emphasized the crosstalk between gut and brain, highlighting how gut composition can influence behavior and brain functions. Thus, the present study investigates the relationship between PANS/PANDAS and gut microbiota ecology. The gut composition of a cohort of 30 patients with PANS/PANDAS was analyzed and compared to control subjects using 16S rRNA-based metagenomics. Data were analyzed for their α- and β-diversity; differences in bacterial distribution were detected by Wilcoxon and LEfSe tests, while metabolic profile was predicted via PICRUSt software. These analyses demonstrate the presence of an altered bacterial community structure in PANS/PANDAS patients with respect to controls. In particular, ecological analysis revealed the presence of two main clusters of subjects based on age range. Thus, to avoid age bias, data from patients and controls were split into two groups: 4–8 years old and >9 years old. The younger PANS/PANDAS group was characterized by a strong increase in Bacteroidetes; in particular, Bacteroides, Odoribacter, and Oscillospira were identified as potential microbial biomarkers of this composition type. Moreover, this group exhibited an increase of several pathways concerning the modulation of the antibody response to inflammation within the gut as well as a decrease in pathways involved in brain function (i.e., SCFA, D-alanine and tyrosine metabolism, and the dopamine pathway). The older group of patients displayed a less uniform bacterial profile, thus impairing the identification of distinct biomarkers. Finally, Pearson’s analysis between bacteria and anti-streptolysin O titer reveled a negative correlation between genera belonging to Firmicutes phylum and anti-streptolysin O while a positive correlation was observed with Odoribacter. In conclusion, this study suggests that streptococcal infections alter gut bacterial communities leading to a pro-inflammatory status through the selection of specific bacterial strains associated with gut inflammation and immune response activation. These findings highlight the possibility of studying bacterial biomarkers associated with this disorder and might led to novel potential therapeutic strategies.
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spelling doaj.art-abe5e091ac894b00867af70b22477d132022-12-21T19:19:55ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2018-04-01910.3389/fmicb.2018.00675334456Gut Microbiota Profiling and Gut–Brain Crosstalk in Children Affected by Pediatric Acute-Onset Neuropsychiatric Syndrome and Pediatric Autoimmune Neuropsychiatric Disorders Associated With Streptococcal InfectionsAndrea Quagliariello0Federica Del Chierico1Alessandra Russo2Sofia Reddel3Giulia Conte4Loris R. Lopetuso5Gianluca Ianiro6Bruno Dallapiccola7Francesco Cardona8Antonio Gasbarrini9Lorenza Putignani10Lorenza Putignani11Unit of Human Microbiome, Bambino Gesù Children’s Hospital, IRCCS, Rome, ItalyUnit of Human Microbiome, Bambino Gesù Children’s Hospital, IRCCS, Rome, ItalyUnit of Human Microbiome, Bambino Gesù Children’s Hospital, IRCCS, Rome, ItalyUnit of Human Microbiome, Bambino Gesù Children’s Hospital, IRCCS, Rome, ItalyDepartment of Human Neurosciences, Sapienza University of Rome, Rome, ItalyDepartment of Internal Medicine, Gastroenterology and Hepatology, Catholic University of the Sacred Heart, Agostino Gemelli Hospital, Rome, ItalyDepartment of Internal Medicine, Gastroenterology and Hepatology, Catholic University of the Sacred Heart, Agostino Gemelli Hospital, Rome, ItalyScientific Directorate, Bambino Gesù Children’s Hospital, IRCCS, Rome, ItalyDepartment of Human Neurosciences, Sapienza University of Rome, Rome, ItalyDepartment of Internal Medicine, Gastroenterology and Hepatology, Catholic University of the Sacred Heart, Agostino Gemelli Hospital, Rome, ItalyUnit of Human Microbiome, Bambino Gesù Children’s Hospital, IRCCS, Rome, ItalyUnit of Parasitology Bambino Gesù Children’s Hospital, IRCCS, Rome, ItalyPediatric acute-onset neuropsychiatric syndrome (PANS) and pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections syndrome (PANDAS) are conditions that impair brain normal neurologic function, resulting in the sudden onset of tics, obsessive-compulsive disorder, and other behavioral symptoms. Recent studies have emphasized the crosstalk between gut and brain, highlighting how gut composition can influence behavior and brain functions. Thus, the present study investigates the relationship between PANS/PANDAS and gut microbiota ecology. The gut composition of a cohort of 30 patients with PANS/PANDAS was analyzed and compared to control subjects using 16S rRNA-based metagenomics. Data were analyzed for their α- and β-diversity; differences in bacterial distribution were detected by Wilcoxon and LEfSe tests, while metabolic profile was predicted via PICRUSt software. These analyses demonstrate the presence of an altered bacterial community structure in PANS/PANDAS patients with respect to controls. In particular, ecological analysis revealed the presence of two main clusters of subjects based on age range. Thus, to avoid age bias, data from patients and controls were split into two groups: 4–8 years old and >9 years old. The younger PANS/PANDAS group was characterized by a strong increase in Bacteroidetes; in particular, Bacteroides, Odoribacter, and Oscillospira were identified as potential microbial biomarkers of this composition type. Moreover, this group exhibited an increase of several pathways concerning the modulation of the antibody response to inflammation within the gut as well as a decrease in pathways involved in brain function (i.e., SCFA, D-alanine and tyrosine metabolism, and the dopamine pathway). The older group of patients displayed a less uniform bacterial profile, thus impairing the identification of distinct biomarkers. Finally, Pearson’s analysis between bacteria and anti-streptolysin O titer reveled a negative correlation between genera belonging to Firmicutes phylum and anti-streptolysin O while a positive correlation was observed with Odoribacter. In conclusion, this study suggests that streptococcal infections alter gut bacterial communities leading to a pro-inflammatory status through the selection of specific bacterial strains associated with gut inflammation and immune response activation. These findings highlight the possibility of studying bacterial biomarkers associated with this disorder and might led to novel potential therapeutic strategies.http://journal.frontiersin.org/article/10.3389/fmicb.2018.00675/fullPANSPANDASgut microbiotadysbiosisbacterial biomarkers
spellingShingle Andrea Quagliariello
Federica Del Chierico
Alessandra Russo
Sofia Reddel
Giulia Conte
Loris R. Lopetuso
Gianluca Ianiro
Bruno Dallapiccola
Francesco Cardona
Antonio Gasbarrini
Lorenza Putignani
Lorenza Putignani
Gut Microbiota Profiling and Gut–Brain Crosstalk in Children Affected by Pediatric Acute-Onset Neuropsychiatric Syndrome and Pediatric Autoimmune Neuropsychiatric Disorders Associated With Streptococcal Infections
Frontiers in Microbiology
PANS
PANDAS
gut microbiota
dysbiosis
bacterial biomarkers
title Gut Microbiota Profiling and Gut–Brain Crosstalk in Children Affected by Pediatric Acute-Onset Neuropsychiatric Syndrome and Pediatric Autoimmune Neuropsychiatric Disorders Associated With Streptococcal Infections
title_full Gut Microbiota Profiling and Gut–Brain Crosstalk in Children Affected by Pediatric Acute-Onset Neuropsychiatric Syndrome and Pediatric Autoimmune Neuropsychiatric Disorders Associated With Streptococcal Infections
title_fullStr Gut Microbiota Profiling and Gut–Brain Crosstalk in Children Affected by Pediatric Acute-Onset Neuropsychiatric Syndrome and Pediatric Autoimmune Neuropsychiatric Disorders Associated With Streptococcal Infections
title_full_unstemmed Gut Microbiota Profiling and Gut–Brain Crosstalk in Children Affected by Pediatric Acute-Onset Neuropsychiatric Syndrome and Pediatric Autoimmune Neuropsychiatric Disorders Associated With Streptococcal Infections
title_short Gut Microbiota Profiling and Gut–Brain Crosstalk in Children Affected by Pediatric Acute-Onset Neuropsychiatric Syndrome and Pediatric Autoimmune Neuropsychiatric Disorders Associated With Streptococcal Infections
title_sort gut microbiota profiling and gut brain crosstalk in children affected by pediatric acute onset neuropsychiatric syndrome and pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections
topic PANS
PANDAS
gut microbiota
dysbiosis
bacterial biomarkers
url http://journal.frontiersin.org/article/10.3389/fmicb.2018.00675/full
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