GEO series
Host-derived bile acids drive dysbiosis by selecting bile-resistant epimerizing bacteria in inflammatory bowel disease
GSE335355
Homo sapiens
Expression profiling by high throughput sequencing
15 samples
Submitted 2026/08/08
Platform GPL34284
Summary
The gut microbiome is a key regulator of intestinal homeostasis. Although dysbiosis is pervasively reported in inflammatory bowel diseases (IBD), its drivers and impact in disease pathophysiology are not yet fully understood. By integrating public metagenomic and metabolomic datasets from >5000 individuals across 12 ethnically diverse cohorts with independent validation cohorts and using neural-network based feature attribution, we identified epimerized bile acids (BAs) produced by microbial hydroxysteroid dehydrogenases (HSDHs) as a novel hallmark of IBD-associated dysbiosis. This shift occurs alongside previously reported changes including a depletion of microbe-derived C7-dehydroxylated BAs and an accumulation of host-derived C7-hydroxylated BAs. We show that increased levels of host-derived BA lead to epithelial remodelling during disease and are sufficient to recapitulate key features of IBD-related dysbiosis, including reduced microbial diversity and expansion of bile-resistant bacteria such as Mediterraneibacter gnavus and Escherichia coli. HSDHs found in IBD-enriched bacteria facilitate growth under high host-derived BA conditions by converting these molecules into urso- and iso-forms. While epimerized 7α-dehydroxylated BA have established immunoregulatory properties, the function of host-derived BA epimers remain poorly understood. We demonstrate that epimerized host-derived BAs exhibit reduced FXR agonist activity and that increased levels of these metabolites, or the bacteria that produce them, are associated with diminished ileal FXR signaling and altered circulating FGF19 and C4 levels in IBD patients. Our findings identify enhanced BA epimerization as a defining metabolic feature of IBD-associated dysbiosis and reveal a mechanism by which bile-resistant bacteria reshape BA signaling, linking microbial adaptation, impaired host-microbiome feedback regulation, and intestinal inflammation.
This dataset
Download
Direct links to NCBI, no account and no request form: the whole study as GSE335355_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 15 samples. Raw sequencing reads are also available from ENA.
Also filed as BioProject PRJNA1477981 and SRA study SRP709241. Searching any of these in the dataset finder brings you back here.
Study design
15 conditions, each sampled once — no replicated groups
Read from 15 sample titles: 15 distinct titles with little repetition. Check it against the sample list below before relying on it.
Samples in this study
0 selected
- GSM9812447 Ile2, pt1, GW
- GSM9812448 Ile3, pt1, veh
- GSM9812449 Ile5, pt2, GW
- GSM9812450 Ile6, pt2, veh
- GSM9812451 Ile8, pt3, GW
- GSM9812452 Ile9, pt3, veh
- GSM9812453 Col1, pt1, CDCA
- GSM9812454 Col2, pt1, GW
- GSM9812455 Col3, pt1, veh
- GSM9812456 Col4, pt2, CDCA
- GSM9812457 Col5, pt2, GW
- GSM9812458 Col6, pt2, veh
- GSM9812459 Col7, pt3, CDCA
- GSM9812460 Col8, pt3, GW
- GSM9812461 Col9, pt3, veh
Similar datasets
- GSE282122 A longitudinal single-cell atlas of anti-tumour necrosis factor treatment in inflammatory bowel disease 216 samples
- GSE328048 Single-cell transcriptome reveals keratinocyte subclusters that contribute to altered differentiation and inflammatory responses in atopic dermatitis 116 samples
- GSE202379 Single Nuclei RNA-Seq to map progression of non-alcoholic fatty liver disease (NAFLD) in patients II 59 samples
- GSE267718 Single cell RNA sequencing (scRNAseq) of urine-derived cells, peripheral blood mononuclear (PBMC), and tumor cells from bladder cancer patients. 33 samples
- GSE226176 Expression data of multiple myeloma patients at various stages of disease 23 samples
- GSE303346 Single-Cell RNA-Seq Reveals Immunosuppressive Effects of Triple-Negative Breast Cancer–Derived Exosomes on NK Cell Responses 16 samples
- GSE220774 Side- and disease-dependent changes in human aortic valve cell population and transcriptomic heterogeneity determined by single-cell RNA sequencing 15 samples
- GSE303509 Biomarker-guided responses in patient-derived organoids predict effective therapies in breast cancer 14 samples
Share this dataset
Metadata from NCBI GEO, cached and refreshed periodically — the NCBI page above is authoritative. Downloads link straight to NCBI/ENA; nothing is proxied through BioTransfer.