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Multi-omics Reveal Vitamin D Regulation of Immune-Gut Microbiome Interactions and Tolerogenic Pathways in Inflammatory Bowel Disease

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Dataset overview

Participants 48
Samples 96
Reuse readiness 6.4/10 evidence-backed score

Multi-omics reveal vitamin D regulation of immune-gut microbiome interactions and tolerogenic pathways in inflammatory bowel disease.

Gubatan J, Sojwal RS, Ye J, Boye TL, Hoang JN, Fardeen T, Temby M, Rubin SJS, et al. · Cell reports. Medicine · 2026

Abstract

Loss of immune tolerance to the gut microbiome plays a pathogenic role in inflammatory bowel disease (IBD). How dietary factors alter host immune-gut microbiome interactions in IBD is unclear. Here, we apply multi-omics (immunoglobulin A or G and 16S rRNA sequencing [IgA-seq, IgG-seq], blood single-cell RNA sequencing [scRNA-seq], and immune repertoire sequencing) to investigate the effects of 12 weeks of vitamin D on host immune microbe interactions in patients with IBD. Vitamin D treatment associates with decreased disease activity and inflammatory markers and increased IgA-bound and decreased IgG-bound gut microbiota. Vitamin D alters the profiles of IgA-bound (increased Lachnospiraceae, Blautia) and IgG-bound (decreased Proteobacteria, Enterococcaceae) gut bacteria. Vitamin D increases B cell activating factor (BAFF) signaling between plasmacytoid dendritic cells and B cells, alters BCR and TCR clonotypes that associate with Ig-bound gut microbiota, and increases α4β7+ B and T regulatory cells. Our results demonstrate that vitamin D promotes immune tolerance to gut microbiota in patients with IBD. Clinical trial is registered under NCT04828031.

doi:10.1016/j.xcrm.2026.102703 ↗ PMID 41895287 ↗ PMC13130636 ↗

Study facts

Organism
Homo sapiens
Platform
NovaSeq X Plus
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
  • Feature/OTU tables are advertised
  • Participant-to-sample mapping is available
  • Participant counts are documented
  • Sample counts are documented

Limitations

  • 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

FieldValueEvidence
assay.platform NovaSeq X Plus
Libraries were sequenced using the NovaSeq X Plus sequencer

Section STAR Methods; PBMC scRNA-seq, scBCR-seq, scTCR-seq processing, offset —

Cohort

FieldValueEvidence
cohort.age_group adult
Patients who met inclusion criteria (adult patients (18 years or older) with inflammatory bowel disease...)

Section STAR Methods; Vitamin D inflammatory bowel disease clinical trial NCT04828031, offset —
cohort.disease_activity_metadata_available True
Disease activity scores (partial Mayo score for ulcerative colitis, Harvey Bradshaw Index for Crohn’s disease)... were collected at week 0 and week 12.

Section STAR Methods; Vitamin D inflammatory bowel disease clinical trial NCT04828031, offset —
cohort.study_design longitudinal
At the time of enrollment (week 0), patients had blood and stool samples collected... Blood and stool samples were collected at the end of study (week 12).

Section STAR Methods; Vitamin D inflammatory bowel disease clinical trial NCT04828031, offset —
cohort.total_participants 48 from source
scRNA-seq from peripheral blood mononuclear cells from 48 patients with inflammatory bowel disease before and after vitamin D intervention

Section study.overall_design, offset —
cohort.treatment_exposure_documented True
Patients were then treated with 50,000 units of oral vitamin D (ergocalciferol) once per week for 12 weeks.

Section STAR Methods; Vitamin D inflammatory bowel disease clinical trial NCT04828031, offset —
cohort.treatment_response_metadata_available True
Disease activity scores... quality of life scores... were collected at week 0 and week 12.

Section STAR Methods; Vitamin D inflammatory bowel disease clinical trial NCT04828031, offset —

Data_Assets

FieldValueEvidence
data_assets.analysis_code False
No custom code was generated in this study.

Section Data and code availability, offset —
data_assets.feature_or_otu_table True
to generate raw cell by gene matrices

Section STAR Methods; PBMC scRNA-seq, scBCR-seq, scTCR-seq processing, offset —
data_assets.open_access True inferred
All scRNA-seq and immune repertoire data generated during this study are available at the Gene Expression Omnibus (GEO) under accession number GSE319270.

Section Data and code availability, offset —
data_assets.pipeline_or_tool_versions True
Fastq files were processed using BD’s Rhapsody analysis pipeline... The R package Seurat V5 was used

Section STAR Methods; PBMC scRNA-seq, scBCR-seq, scTCR-seq processing, offset —
data_assets.qc_or_negative_controls_reported True
The R package Seurat V5 was used to filter out low quality cells

Section STAR Methods; PBMC scRNA-seq, scBCR-seq, scTCR-seq processing, offset —
data_assets.raw_reads True
All scRNA-seq and immune repertoire data generated during this study are available at the Gene Expression Omnibus (GEO) under accession number GSE319270.

Section Data and code availability, offset —

Specimens

FieldValueEvidence
specimens.body_site peripheral blood
scRNA-seq from peripheral blood mononuclear cells from 48 patients with inflammatory bowel disease

Section study.overall_design, offset —
specimens.longitudinal_sampling True
from 48 patients with inflammatory bowel disease before and after vitamin D intervention

Section study.overall_design, offset —
specimens.number_of_samples 96 computed
n = 48 patients samples, two time points

Section Results; scRNA-seq reveals effects on PBMC composition, offset —
specimens.participant_to_sample_mapping_available True inferred
n = 48 patients samples, two time points

Section Results; scRNA-seq reveals effects on PBMC composition, offset —