Related Experiment Video
Updated: May 28, 2025
Chronic Salmonella Infection Induced Intestinal Fibrosis
Published on: September 22, 2019
Deep Sequencing of Crohn's Disease Lamina Propria Phagocytes Identifies Pathobionts and Correlates With
Gillian E Jacobsen1,2,3, Eddy E Gonzalez3, Payton Mendygral3
1Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, FL, USA.
Background:
Crohn's disease (CD) is characterized by an inflammatory response to gut microbiota. Macrophages and dendritic cells play an active role in CD inflammation. Specific microbiota have been implicated in the pathogenesis of ileal CD. We investigated the phagocyte-associated microbiome using an unbiased sequencing approach to identify potential pathobionts and elucidate the host response to these microbes.
Methods:
We collected ileal and colonic mucosal biopsies from CD patients and controls without inflammatory bowel disease (IBD), isolated lamina propria phagocytes (CD11b+ cells), and performed deep RNA sequencing (n = 37). Reads were mapped to the human genome for host gene expression analysis and a prokaryotic database for microbiome taxonomic and metatranscriptomic profiling. Results were confirmed in a second IBD cohort (n = 17). Lysed lamina propria cells were plated for bacterial culturing; isolated colonies underwent whole genome sequencing (n = 11).
Results:
Crohn's disease ileal phagocytes contained higher relative abundances of Escherichia coli, Ruminococcus gnavus, and Enterocloster spp. than those from controls. CD phagocyte-associated microbes had increased expression of lipopolysaccharide (LPS) biosynthesis pathways. Phagocytes with a higher pathobiont burden showed increased expression of pro-inflammatory and antimicrobial genes, including PI3 (antimicrobial peptide) and BPIFB1 (LPS-binding molecule). E. coli isolated from the CD lamina propria had more flagellar motility and antibiotic resistance genes than control-derived strains.
Conclusions:
Lamina propria resident phagocytes harbor bacterial strains that may act as pathobionts in CD. Our findings shed light on the role of pathobionts and the immune response in CD pathogenesis and suggest new targets for therapies.
Insights
Phagocytes in Crohn's disease (CD) ileum harbor specific bacteria like E. coli, which show increased inflammatory gene expression in the host. These findings reveal potential pathobionts and immune targets for CD therapies.
Area of Science:
- Gastroenterology
- Immunology
- Microbiome Research
Background:
- Crohn's disease (CD) involves an inflammatory response to gut microbiota.
- Macrophages and dendritic cells are key players in CD inflammation.
- Specific gut microbes are implicated in the pathogenesis of ileal CD.
Purpose of the Study:
- To investigate the phagocyte-associated microbiome in CD using unbiased sequencing.
- To identify potential pathobionts contributing to CD.
- To understand the host immune response to these microbes.
Main Methods:
- Collected ileal and colonic mucosal biopsies from CD patients and controls.
- Isolated lamina propria phagocytes (CD11b+ cells) for deep RNA sequencing.
- Performed microbiome taxonomic and metatranscriptomic profiling, confirmed in a second cohort.
Main Results:
- Ileal phagocytes in CD showed higher abundances of Escherichia coli, Ruminococcus gnavus, and Enterocloster spp.
- CD-associated microbes exhibited increased lipopolysaccharide (LPS) biosynthesis pathway expression.
- Phagocytes with higher pathobiont burden displayed elevated pro-inflammatory and antimicrobial gene expression.
Conclusions:
- Resident phagocytes in the lamina propria harbor bacterial strains acting as pathobionts in CD.
- Findings illuminate the role of pathobionts and immune response in CD pathogenesis.
- Identified potential new therapeutic targets for CD.
More Related Videos
09:08Investigating Target Gene Function in a CD40 Agonistic Antibody-induced Colitis Model using CRISPR/Cas9-based Technologies
Published on: June 2, 2021
07:05Fluorescence-mediated Tomography for the Detection and Quantification of Macrophage-related Murine Intestinal Inflammation
Published on: December 15, 2017
Related Concept Videos
01:30Inflammatory Bowel Disease II: Crohn's Disease
Inflammatory bowel disease, commonly known as IBD, refers to a collection of disorders that lead to persistent inflammation of the gastrointestinal tract. The two types of IBD are ulcerative colitis, which impacts the colon, and Crohn's disease, which can involve any part of the gastrointestinal segment.
Crohn's disease
Crohn's disease is a chronic, systemic inflammatory bowel disease (IBD) that predominantly affects the gastrointestinal tract. It is marked by...
01:27Inflammatory Bowel Disease I: Ulcerative Colitis
Inflammatory bowel disease, or IBD, encompasses a group of disorders characterized by chronic inflammation or ulceration of the gastrointestinal tract.
Risk Factors
The exact cause of IBD remains unclear, although it is believed to be due to a mix of genetic, environmental, microbial, and immune factors. Genetic factors are significant in determining susceptibility to IBD, with family history being a critical risk factor. Individuals with a first-degree relative who has IBD are at...
01:17Chronic Bowel Disorders: Introduction
Irritable Bowel Syndrome (IBS) is a common disorder affecting the gastrointestinal tract. The distinctive feature is recurrent abdominal pain associated with altered bowel movements, manifesting as constipation, diarrhea, or fluctuating between both. The...