NOD2 Influences Trajectories of Intestinal Microbiota Recovery After Antibiotic Perturbation
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NOD2 Influences Trajectories of Intestinal Microbiota Recovery After Antibiotic Perturbation.
Abstract
<h4>Background & aims</h4>Loss-of-function variants in nucleotide-binding oligomerization domain-containing protein 2 (NOD2) impair the recognition of the bacterial cell wall component muramyl-dipeptide and are associated with an increased risk for developing Crohn's disease. Likewise, exposure to antibiotics increases the individual risk for developing inflammatory bowel disease. Here, we studied the long-term impact of NOD2 on the ability of the gut bacterial and fungal microbiota to recover after antibiotic treatment.<h4>Methods</h4>Two cohorts of 20-week-old and 52-week-old wild-type (WT) C57BL/6J and NOD2 knockout (Nod2-KO) mice were treated with broad-spectrum antibiotics and fecal samples were collected to investigate temporal dynamics of the intestinal microbiota (bacteria and fungi) using 16S ribosomal RNA and internal transcribed spacer 1 sequencing. In addition, 2 sets of germ-free WT mice were colonized with either WT or Nod2-KO after antibiotic donor microbiota and the severity of intestinal inflammation was monitored in the colonized mice.<h4>Results</h4>Antibiotic exposure caused long-term shifts in the bacterial and fungal community composition. Genetic ablation of NOD2 was associated with delayed body weight gain after antibiotic treatment and an impaired recovery of the bacterial gut microbiota. Transfer of the postantibiotic fecal microbiota of Nod2-KO mice induced an intestinal inflammatory response in the colons of germ-free recipient mice compared with respective microbiota from WT controls based on histopathology and gene expression analyses.<h4>Conclusions</h4>Our data show that the bacterial sensor NOD2 contributes to intestinal microbial community composition after antibiotic treatment and may add to the explanation of how defects in the NOD2 signaling pathway are involved in the etiology of Crohn's disease.
doi:10.1016/j.jcmgh.2020.03.008 ↗ PMID 32289499 ↗ PMC7327897 ↗
Study facts
- Organism
- —
- Platform
- Illumina MiSeq
- Age group
- adult
- Disease groups
- —
- 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
Limitations
- Not documented: feature/otu tables are advertised
- Not documented: taxonomic tables are advertised
- Not documented: participant counts are documented
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 |
MiSeq with 2 × 300 base pairs Section |
assay.platform |
Illumina MiSeq |
sequenced on an Illumina ... MiSeq with 2 × 300 base pairs Section |
assay.primers_reported |
True |
using the primers ITS1-F(F) ... and ITS2(R) ... to amplify the fungal ITS1 region Section |
assay.read_length |
300 |
MiSeq with 2 × 300 base pairs Section |
assay.target_region |
16S rRNA V3–V4 and fungal ITS1 |
The 16S rRNA gene variable region V3–V4 was amplified ... fungal ITS1 ... amplicon sequencing Section |
Cohort
| Field | Value | Evidence |
|---|---|---|
cohort.age_group |
adult |
Two cohorts of 20-week-old and 52-week-old ... mice Section |
cohort.study_design |
longitudinal |
investigate longitudinal dynamics of the bacterial microbiota after a pulsed perturbation Section |
cohort.treatment_exposure_documented |
True |
treated with a cocktail of broad-spectrum antibiotics composed of ampicillin ... vancomycin ... neomycin ... and metronidazole Section |
cohort.treatment_response_metadata_available |
True |
Recovery from antibiotic-induced weight loss occurred earlier and faster in WT mice compared with Nod2-KO mice Section |
Data_Assets
| Field | Value | Evidence |
|---|---|---|
data_assets.open_access |
True from source |
"isOpenAccess": "Y" Section |
data_assets.pipeline_or_tool_versions |
True |
using Mothur and MacQIIME v1.9.1 Section |
data_assets.qc_or_negative_controls_reported |
True |
Only sequences with less than 450 base pairs ... mean quality score ≥25 were considered Section |
data_assets.raw_reads |
True |
Raw sequencing data ... were uploaded to ... ENA under accession number PRJEB21817 Section |
Specimens
| Field | Value | Evidence |
|---|---|---|
specimens.body_site |
gut |
the gut bacterial and fungal microbiota to recover after antibiotic treatment Section |
specimens.longitudinal_sampling |
True |
16S amplicon sequencing was performed on longitudinally sampled fecal material Section |
specimens.participant_to_sample_mapping_available |
True inferred |
Each dot represents the bacterial composition of an individual fecal sample. Section |
specimens.sample_type |
stool |
Fecal pellets were collected immediately from mice throughout the experiment and stored at -80°C. Section |