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Characterization of the Mucosally-Adherent Duodenal Microbiome in Children with and without Crohn’s Disease

Manipulation of the microbiome is a rational treatment strategy for inflammatory bowel disease (IBD). Compared to the colon and terminal ileum (TI), understanding of the microbial composition in the duodenum is sparse. This gap in knowledge is especially significant for children with Crohn’s disease...

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Autores principales: Schmidt, Kenneth, Noel-MacDonnell, Janelle, Vyhlidal, Carrie, Heruth, Daniel P., Singh, Vivekanand, Ahmed, Atif A., Hudson, Taina, Williams, Veronica, Shakhnovich, Valentina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9317548/
https://www.ncbi.nlm.nih.gov/pubmed/35890149
http://dx.doi.org/10.3390/ph15070850
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author Schmidt, Kenneth
Noel-MacDonnell, Janelle
Vyhlidal, Carrie
Heruth, Daniel P.
Singh, Vivekanand
Ahmed, Atif A.
Hudson, Taina
Williams, Veronica
Shakhnovich, Valentina
author_facet Schmidt, Kenneth
Noel-MacDonnell, Janelle
Vyhlidal, Carrie
Heruth, Daniel P.
Singh, Vivekanand
Ahmed, Atif A.
Hudson, Taina
Williams, Veronica
Shakhnovich, Valentina
author_sort Schmidt, Kenneth
collection PubMed
description Manipulation of the microbiome is a rational treatment strategy for inflammatory bowel disease (IBD). Compared to the colon and terminal ileum (TI), understanding of the microbial composition in the duodenum is sparse. This gap in knowledge is especially significant for children with Crohn’s disease (CD) because the prevalence of duodenal CD is higher in children than in adults. Our aim was to characterize the bacterial composition of the mucosally-adherent duodenal microbiome in children with and without CD as a first step toward development of targeted IBD treatment strategies at this disease location. Fresh-frozen mucosal biopsies were obtained from the duodenum and TI of children with treatment-naïve CD and age- and sex-matched controls. Extracted DNA was analyzed for sequence variation in the 16S ribosomal RNA bacterial gene region V4 (Novogene; Beijing, China). Bacterial relative abundance, alpha and beta composition, and diversity, were compared across duodenal and TI samples from the controls and CD groups with and without chronic active inflammation (118 samples from 73 children total; approx. 50% CD), using UniFrac dissimilarity coefficients (α < 0.05), Linear Discriminant Analysis Effect Size (LEfSe) analysis (LDA score ≥ 2), and Unweighted Pair Group Method with Arithmetic Mean (UPGMA) analysis. The relationships between bacterial abundance, sex, age, concomitant medication use, and villous length were assessed. The microbial composition in the duodenum was significantly different from the TI in the control population(R-value = 0.558, p = 0.001) and in children with active CD (R-value = 0.301, p = 0.001). Significant differences in bacterial abundance were noted between the control and CD duodena (LDA > 4). The duodenum of children without CD was characterized by increased abundance in Pseudomonodales, whereas the actively inflamed duodenum in CD was characterized by increased abundance of Bacteroidales, specifically the family Prevotellaceae. This trend is opposite of previously published observations of microbial composition in the TI, where active inflammation was associated with a relative decrease in the abundance of Bacteroidetes and an increase in Proteobacteria, including Pseudomonadales. No statistically significant correlations were noted between abundance and age, sex, concomitant medication use or villous length, except for Bacteroidetes, which significantly decreased in abundance in the TI with age (p = 0.048). The pediatric duodenal microbiome is distinct from the TI and characterized by an increased abundance of Pseudomonodales and Spirochetes in healthy children, and an increased abundance of Bacteroidales in active CD patients.
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spelling pubmed-93175482022-07-27 Characterization of the Mucosally-Adherent Duodenal Microbiome in Children with and without Crohn’s Disease Schmidt, Kenneth Noel-MacDonnell, Janelle Vyhlidal, Carrie Heruth, Daniel P. Singh, Vivekanand Ahmed, Atif A. Hudson, Taina Williams, Veronica Shakhnovich, Valentina Pharmaceuticals (Basel) Article Manipulation of the microbiome is a rational treatment strategy for inflammatory bowel disease (IBD). Compared to the colon and terminal ileum (TI), understanding of the microbial composition in the duodenum is sparse. This gap in knowledge is especially significant for children with Crohn’s disease (CD) because the prevalence of duodenal CD is higher in children than in adults. Our aim was to characterize the bacterial composition of the mucosally-adherent duodenal microbiome in children with and without CD as a first step toward development of targeted IBD treatment strategies at this disease location. Fresh-frozen mucosal biopsies were obtained from the duodenum and TI of children with treatment-naïve CD and age- and sex-matched controls. Extracted DNA was analyzed for sequence variation in the 16S ribosomal RNA bacterial gene region V4 (Novogene; Beijing, China). Bacterial relative abundance, alpha and beta composition, and diversity, were compared across duodenal and TI samples from the controls and CD groups with and without chronic active inflammation (118 samples from 73 children total; approx. 50% CD), using UniFrac dissimilarity coefficients (α < 0.05), Linear Discriminant Analysis Effect Size (LEfSe) analysis (LDA score ≥ 2), and Unweighted Pair Group Method with Arithmetic Mean (UPGMA) analysis. The relationships between bacterial abundance, sex, age, concomitant medication use, and villous length were assessed. The microbial composition in the duodenum was significantly different from the TI in the control population(R-value = 0.558, p = 0.001) and in children with active CD (R-value = 0.301, p = 0.001). Significant differences in bacterial abundance were noted between the control and CD duodena (LDA > 4). The duodenum of children without CD was characterized by increased abundance in Pseudomonodales, whereas the actively inflamed duodenum in CD was characterized by increased abundance of Bacteroidales, specifically the family Prevotellaceae. This trend is opposite of previously published observations of microbial composition in the TI, where active inflammation was associated with a relative decrease in the abundance of Bacteroidetes and an increase in Proteobacteria, including Pseudomonadales. No statistically significant correlations were noted between abundance and age, sex, concomitant medication use or villous length, except for Bacteroidetes, which significantly decreased in abundance in the TI with age (p = 0.048). The pediatric duodenal microbiome is distinct from the TI and characterized by an increased abundance of Pseudomonodales and Spirochetes in healthy children, and an increased abundance of Bacteroidales in active CD patients. MDPI 2022-07-11 /pmc/articles/PMC9317548/ /pubmed/35890149 http://dx.doi.org/10.3390/ph15070850 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Schmidt, Kenneth
Noel-MacDonnell, Janelle
Vyhlidal, Carrie
Heruth, Daniel P.
Singh, Vivekanand
Ahmed, Atif A.
Hudson, Taina
Williams, Veronica
Shakhnovich, Valentina
Characterization of the Mucosally-Adherent Duodenal Microbiome in Children with and without Crohn’s Disease
title Characterization of the Mucosally-Adherent Duodenal Microbiome in Children with and without Crohn’s Disease
title_full Characterization of the Mucosally-Adherent Duodenal Microbiome in Children with and without Crohn’s Disease
title_fullStr Characterization of the Mucosally-Adherent Duodenal Microbiome in Children with and without Crohn’s Disease
title_full_unstemmed Characterization of the Mucosally-Adherent Duodenal Microbiome in Children with and without Crohn’s Disease
title_short Characterization of the Mucosally-Adherent Duodenal Microbiome in Children with and without Crohn’s Disease
title_sort characterization of the mucosally-adherent duodenal microbiome in children with and without crohn’s disease
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9317548/
https://www.ncbi.nlm.nih.gov/pubmed/35890149
http://dx.doi.org/10.3390/ph15070850
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