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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MDPI AG
2022-07-01
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| Online Access: | https://www.mdpi.com/1424-8247/15/7/850 |
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| author | Kenneth Schmidt Janelle Noel-MacDonnell Carrie Vyhlidal Daniel P. Heruth Vivekanand Singh Atif A. Ahmed Taina Hudson Veronica Williams Valentina Shakhnovich |
| author_facet | Kenneth Schmidt Janelle Noel-MacDonnell Carrie Vyhlidal Daniel P. Heruth Vivekanand Singh Atif A. Ahmed Taina Hudson Veronica Williams Valentina Shakhnovich |
| author_sort | Kenneth Schmidt |
| collection | DOAJ |
| 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, <i>p</i> = 0.001) and in children with active CD (R-value = 0.301, <i>p</i> = 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 (<i>p</i> = 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. |
| first_indexed | 2024-03-09T06:04:48Z |
| format | Article |
| id | doaj.art-d53ab0148bba4a07ae051ac944509956 |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-09T06:04:48Z |
| publishDate | 2022-07-01 |
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| series | Pharmaceuticals |
| spelling | doaj.art-d53ab0148bba4a07ae051ac9445099562023-12-03T12:05:37ZengMDPI AGPharmaceuticals1424-82472022-07-0115785010.3390/ph15070850Characterization of the Mucosally-Adherent Duodenal Microbiome in Children with and without Crohn’s DiseaseKenneth Schmidt0Janelle Noel-MacDonnell1Carrie Vyhlidal2Daniel P. Heruth3Vivekanand Singh4Atif A. Ahmed5Taina Hudson6Veronica Williams7Valentina Shakhnovich8School of Medicine, University of Missouri Kansas City, Kansas City, MO 64108, USASchool of Medicine, University of Missouri Kansas City, Kansas City, MO 64108, USAKCAS Bioanalytical & Biomarker Services, Shawnee, KS 66061, USASchool of Medicine, University of Missouri Kansas City, Kansas City, MO 64108, USADepartment of Pathology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USASeattle Children’s Hospitals, Seattle, WA 98105, USASchool of Medicine, University of Missouri Kansas City, Kansas City, MO 64108, USASchool of Medicine, University of Missouri Kansas City, Kansas City, MO 64108, USASchool of Medicine, University of Missouri Kansas City, Kansas City, MO 64108, USAManipulation 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, <i>p</i> = 0.001) and in children with active CD (R-value = 0.301, <i>p</i> = 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 (<i>p</i> = 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.https://www.mdpi.com/1424-8247/15/7/850inflammatory bowel diseaseCrohn’s diseaseduodenummicrobiomepediatricsmall intestine |
| spellingShingle | Kenneth Schmidt Janelle Noel-MacDonnell Carrie Vyhlidal Daniel P. Heruth Vivekanand Singh Atif A. Ahmed Taina Hudson Veronica Williams Valentina Shakhnovich Characterization of the Mucosally-Adherent Duodenal Microbiome in Children with and without Crohn’s Disease Pharmaceuticals inflammatory bowel disease Crohn’s disease duodenum microbiome pediatric small intestine |
| 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 | inflammatory bowel disease Crohn’s disease duodenum microbiome pediatric small intestine |
| url | https://www.mdpi.com/1424-8247/15/7/850 |
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