Phagocyte-Associated Pathobionts in Crohn's Disease

Dataset overview

Participants 25

Samples 37

Reuse readiness 6.4/10 evidence-backed score

Deep Sequencing of Crohn's Disease Lamina Propria Phagocytes Identifies Pathobionts and Correlates With Pro-Inflammatory Gene Expression.

Jacobsen GE, Gonzalez EE, Mendygral P, Faust KM, Hazime H, Fernandez I, Santander AM, Quintero MA, et al. · Inflammatory bowel diseases · 2025

Abstract

<h4>Background</h4>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.<h4>Methods</h4>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).<h4>Results</h4>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.<h4>Conclusions</h4>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.

doi:10.1093/ibd/izae316 ↗ PMID 39951038 ↗ PMC12069990 ↗

Study facts

Organism: Homo sapiens
Platform: Illumina NovaSeqX
Age group: adult
Disease groups: Crohn's disease, Non-IBD controls
Anatomical sites: —

Data availability

Specific data assets have not been resolved from the source yet — see the source repository below for the full file listing.

Strengths & limitations for reuse

Strengths

Raw reads are advertised
Participant-to-sample mapping is available
Participant counts are documented
Sample counts are documented

Limitations

Not documented: feature/otu tables are advertised
Not documented: taxonomic tables are advertised

Extraction evidence & provenance

Each extracted field is shown with the source excerpt and location used to resolve it.

Assay

Field	Value	Evidence
`assay.paired_end`	True	>100M PE150 reads were generated per sample. Section `Methods—RNA Sequencing`, offset 7700
`assay.platform`	Illumina NovaSeqX	Libraries were sequenced on 6 lanes of Illumina NovaSeqX Section `Methods—RNA Sequencing`, offset 7700
`assay.read_length`	150	>100M PE150 reads were generated per sample. Section `Methods—RNA Sequencing`, offset 7700
`assay.sequencing_type`	metatranscriptomics	we were able to subsequently characterize the phagocyte-associated microbiome and metatranscriptome in CD and control samples. Section `Methods—RNA Sequencing Bioinformatics Analysis`, offset 8800

Cohort

Field	Value	Evidence
`cohort.age_group`	adult	our controls (age range: 52-70) were older than our CD patients (age range: 23-68) Section `Discussion—Limitations`, offset 50000
`cohort.crohns_disease_participants`	15	We isolated CD11b + cells from 50 gut mucosal biopsy samples from 15 CD patients and 10 controls Section `Results—Patient and Sample Characteristics`, offset 15000
`cohort.disease_activity_metadata_available`	True	Site inflammation was determined from the endoscopist’s interpretation and the pathologist’s histology report. Section `Methods—Subject Enrollment and Sample Collection`, offset 4200
`cohort.non_ibd_controls`	10	We isolated CD11b + cells from 50 gut mucosal biopsy samples from 15 CD patients and 10 controls Section `Results—Patient and Sample Characteristics`, offset 15000
`cohort.study_design`	cross_sectional inferred	Samples were collected from inflamed sites when possible... Four to 6 gut mucosal biopsies were taken from the terminal ileum and/or ascending colon Section `Methods—Subject Enrollment and Sample Collection`, offset 4200
`cohort.total_participants`	25 computed	We isolated CD11b + cells from 50 gut mucosal biopsy samples from 15 CD patients and 10 controls Section `Results—Patient and Sample Characteristics`, offset 15000
`cohort.treatment_exposure_documented`	True	We included CD patients with different phenotypes ... and current treatments (none, mesalamines, anti-tumor necrosis factor [TNF], anti-IL12/23, or Janus kinase [JAK] inhibitors) Section `Results—Patient and Sample Characteristics`, offset 14500

Data_Assets

Field Value Evidence

Field	Value	Evidence
`data_assets.pipeline_or_tool_versions`	True	Host and microbial RNA sequencing analyses were performed using CLC Genomics Workbench v23.0 and v24.0 (QIAGEN). Section `Methods—RNA Sequencing Bioinformatics Analysis`, offset 9200
`data_assets.raw_reads`	True	The RNA sequencing data generated in this study have been deposited to the National Center for Biotechnology Information (NCBI)’s Gene Expression Omnibus (GEO) with accession number GSE267465. Section `Data availability`, offset 59000

data_assets.pipeline_or_tool_versions

True

Host and microbial RNA sequencing analyses were performed using CLC Genomics Workbench v23.0 and v24.0 (QIAGEN).

Section Methods—RNA Sequencing Bioinformatics Analysis, offset 9200

data_assets.raw_reads

True

The RNA sequencing data generated in this study have been deposited to the National Center for Biotechnology Information (NCBI)’s Gene Expression Omnibus (GEO) with accession number GSE267465.

Section Data availability, offset 59000

Specimens

Field	Value	Evidence
`specimens.body_site`	terminal ileum and ascending colon	Four to 6 gut mucosal biopsies were taken from the terminal ileum and/or ascending colon Section `Methods—Subject Enrollment and Sample Collection`, offset 4200
`specimens.inflamed_status_available`	True	Site inflammation was determined from the endoscopist’s interpretation and the pathologist’s histology report. Section `Methods—Subject Enrollment and Sample Collection`, offset 4200
`specimens.number_of_samples`	37	Sufficient quantities of RNA for sequencing were obtained from 37 samples. Section `Methods—RNA Sequencing`, offset 7600
`specimens.participant_to_sample_mapping_available`	True inferred	We isolated CD11b + cells from 50 gut mucosal biopsy samples from 15 CD patients and 10 controls Section `Results—Patient and Sample Characteristics`, offset 15000
`specimens.sample_type`	mucosal_biopsy	Four to 6 gut mucosal biopsies were taken from the terminal ileum and/or ascending colon Section `Methods—Subject Enrollment and Sample Collection`, offset 4200