Distinctive Microbial Signatures and Gut-Brain Crosstalk in Pediatric Patients with Coeliac Disease and Type 1 Diabetes Mellitus

Coeliac disease (CD) and Type 1 diabetes mellitus (T1DM) are immune-mediated diseases. Emerging evidence suggests that dysbiosis in the gut microbiome plays a role in the pathogenesis of both diseases and may also be associated with the development of neuropathy. The primary goal in this cross-secti...

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Main Authors: Parul Singh, Arun Rawat, Bara Al-Jarrah, Saras Saraswathi, Hoda Gad, Mamoun Elawad, Khalid Hussain, Mohammed A. Hendaus, Wesam Al-Masri, Rayaz A. Malik, Souhaila Al Khodor, Anthony K. Akobeng
Format: Article
Language:English
Published: MDPI AG 2021-02-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/22/4/1511
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author Parul Singh
Arun Rawat
Bara Al-Jarrah
Saras Saraswathi
Hoda Gad
Mamoun Elawad
Khalid Hussain
Mohammed A. Hendaus
Wesam Al-Masri
Rayaz A. Malik
Souhaila Al Khodor
Anthony K. Akobeng
author_facet Parul Singh
Arun Rawat
Bara Al-Jarrah
Saras Saraswathi
Hoda Gad
Mamoun Elawad
Khalid Hussain
Mohammed A. Hendaus
Wesam Al-Masri
Rayaz A. Malik
Souhaila Al Khodor
Anthony K. Akobeng
author_sort Parul Singh
collection DOAJ
description Coeliac disease (CD) and Type 1 diabetes mellitus (T1DM) are immune-mediated diseases. Emerging evidence suggests that dysbiosis in the gut microbiome plays a role in the pathogenesis of both diseases and may also be associated with the development of neuropathy. The primary goal in this cross-sectional pilot study was to identify whether there are distinct gut microbiota alterations in children with CD (<i>n</i> = 19), T1DM (<i>n</i> = 18) and both CD and T1DM (<i>n</i> = 9) compared to healthy controls (<i>n</i> = 12). Our second goal was to explore the relationship between neuropathy (corneal nerve fiber damage) and the gut microbiome composition. Microbiota composition was determined by 16S rRNA gene sequencing. Corneal confocal microscopy was used to determine nerve fiber damage. There was a significant difference in the overall microbial diversity between the four groups with healthy controls having a greater microbial diversity as compared to the patients. The abundance of pathogenic proteobacteria <i>Shigella</i> and <i>E. coli</i> were significantly higher in CD patients. Differential abundance analysis showed that several bacterial amplicon sequence variants (ASVs) distinguished CD from T1DM. The tissue transglutaminase antibody correlated significantly with a decrease in gut microbial diversity. Furthermore, the Bacteroidetes phylum, specifically the genus <i>Parabacteroides</i> was significantly correlated with corneal nerve fiber loss in the subjects with neuropathic damage belonging to the diseased groups. We conclude that disease-specific gut microbial features traceable down to the ASV level distinguish children with CD from T1DM and specific gut microbial signatures may be associated with small fiber neuropathy. Further research on the mechanisms linking altered microbial diversity with neuropathy are warranted.
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spelling doaj.art-8a2aa2183f8c44d097aad787f32a6e062023-12-03T12:14:43ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-02-01224151110.3390/ijms22041511Distinctive Microbial Signatures and Gut-Brain Crosstalk in Pediatric Patients with Coeliac Disease and Type 1 Diabetes MellitusParul Singh0Arun Rawat1Bara Al-Jarrah2Saras Saraswathi3Hoda Gad4Mamoun Elawad5Khalid Hussain6Mohammed A. Hendaus7Wesam Al-Masri8Rayaz A. Malik9Souhaila Al Khodor10Anthony K. Akobeng11Research Department, Sidra Medicine, Doha 26999, QatarResearch Department, Sidra Medicine, Doha 26999, QatarResearch Department, Sidra Medicine, Doha 26999, QatarDivision of Gastroenterology, Hepatology, and Nutrition, Sidra Medicine, Doha 26999, QatarDepartment Medicine, Weill Cornell Medicine-Qatar, Doha 24144, QatarDivision of Gastroenterology, Hepatology, and Nutrition, Sidra Medicine, Doha 26999, QatarDivision of Endocrinology, Sidra Medicine, Doha 26999, QatarDivision of General Pediatrics, Sidra Medicine, Doha 26999, QatarDivision of Gastroenterology, Hepatology, and Nutrition, Sidra Medicine, Doha 26999, QatarDepartment Medicine, Weill Cornell Medicine-Qatar, Doha 24144, QatarResearch Department, Sidra Medicine, Doha 26999, QatarDivision of Gastroenterology, Hepatology, and Nutrition, Sidra Medicine, Doha 26999, QatarCoeliac disease (CD) and Type 1 diabetes mellitus (T1DM) are immune-mediated diseases. Emerging evidence suggests that dysbiosis in the gut microbiome plays a role in the pathogenesis of both diseases and may also be associated with the development of neuropathy. The primary goal in this cross-sectional pilot study was to identify whether there are distinct gut microbiota alterations in children with CD (<i>n</i> = 19), T1DM (<i>n</i> = 18) and both CD and T1DM (<i>n</i> = 9) compared to healthy controls (<i>n</i> = 12). Our second goal was to explore the relationship between neuropathy (corneal nerve fiber damage) and the gut microbiome composition. Microbiota composition was determined by 16S rRNA gene sequencing. Corneal confocal microscopy was used to determine nerve fiber damage. There was a significant difference in the overall microbial diversity between the four groups with healthy controls having a greater microbial diversity as compared to the patients. The abundance of pathogenic proteobacteria <i>Shigella</i> and <i>E. coli</i> were significantly higher in CD patients. Differential abundance analysis showed that several bacterial amplicon sequence variants (ASVs) distinguished CD from T1DM. The tissue transglutaminase antibody correlated significantly with a decrease in gut microbial diversity. Furthermore, the Bacteroidetes phylum, specifically the genus <i>Parabacteroides</i> was significantly correlated with corneal nerve fiber loss in the subjects with neuropathic damage belonging to the diseased groups. We conclude that disease-specific gut microbial features traceable down to the ASV level distinguish children with CD from T1DM and specific gut microbial signatures may be associated with small fiber neuropathy. Further research on the mechanisms linking altered microbial diversity with neuropathy are warranted.https://www.mdpi.com/1422-0067/22/4/1511gut microbiotaT1DMcoeliac diseasechildrenpediatric neuropathycorneal confocal microscopy
spellingShingle Parul Singh
Arun Rawat
Bara Al-Jarrah
Saras Saraswathi
Hoda Gad
Mamoun Elawad
Khalid Hussain
Mohammed A. Hendaus
Wesam Al-Masri
Rayaz A. Malik
Souhaila Al Khodor
Anthony K. Akobeng
Distinctive Microbial Signatures and Gut-Brain Crosstalk in Pediatric Patients with Coeliac Disease and Type 1 Diabetes Mellitus
International Journal of Molecular Sciences
gut microbiota
T1DM
coeliac disease
children
pediatric neuropathy
corneal confocal microscopy
title Distinctive Microbial Signatures and Gut-Brain Crosstalk in Pediatric Patients with Coeliac Disease and Type 1 Diabetes Mellitus
title_full Distinctive Microbial Signatures and Gut-Brain Crosstalk in Pediatric Patients with Coeliac Disease and Type 1 Diabetes Mellitus
title_fullStr Distinctive Microbial Signatures and Gut-Brain Crosstalk in Pediatric Patients with Coeliac Disease and Type 1 Diabetes Mellitus
title_full_unstemmed Distinctive Microbial Signatures and Gut-Brain Crosstalk in Pediatric Patients with Coeliac Disease and Type 1 Diabetes Mellitus
title_short Distinctive Microbial Signatures and Gut-Brain Crosstalk in Pediatric Patients with Coeliac Disease and Type 1 Diabetes Mellitus
title_sort distinctive microbial signatures and gut brain crosstalk in pediatric patients with coeliac disease and type 1 diabetes mellitus
topic gut microbiota
T1DM
coeliac disease
children
pediatric neuropathy
corneal confocal microscopy
url https://www.mdpi.com/1422-0067/22/4/1511
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