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DAV132 colon-targeted adsorbent prevents antibiotic-related dysbiosis in human volunteers and mitigates anti-PD-1 resistance in murine models

GSE251922 Mus musculus (mouse) RNA-seq (gene expression) 39 samples Submitted 2024/08/12 Platform GPL30172
At a glance

RNA-seq (gene expression) · mouse · 39 samples

What it is
RNA-seq (gene expression)Gene activity measured by sequencing. The summary does not mention single-cell work, so this is most likely bulk: one average per sample, the usual starting point for comparing groups.
Organism
Mus musculus (mouse)
Samples
39 samples: 8 conditions, mostly with about 5 replicates eachGroups are read from the sample names, not from the paper. Check the list below.
Data you can get
A processed table (series matrix) and supplementary files from NCBI; the raw sequencing reads from ENA. Which of these hold counts depends on the study, so check the file list.
Paper
The DAV132 colon-targeted adsorbent does not interfere with plasma concentrations of antibiotics but prevents antibiotic-related dysbiosis: a randomized phase I trial in healthy volunteersNature communications · 2024
Summary (written by the submitters)
The deleterious impact of antibiotics (ATB) on the microbiome negatively impacts immune checkpoint inhibitor (ICI) response. We assessed the efficacy of DAV132, a colon-targeted adsorbent in 70 healthy volunteers (HV) randomized to receive ceftazidime-avibactam or piperacillin-tazobactam alone or in combination with oral administration of DAV132.
Read the full summary ↓
DAV132 significantly decreased fecal but not plasma ATB concentration. When coadministered with either ATB, DAV132 prevented loss of microbiome diversity and induced rapid recovery of the baseline microbiota composition. Moreover, bacterial probe set qPCR-based assay confirmed metagenomics results that DAV132 preserved several commensals such as Alistipes shahii, Blautia obeum and Faecalibacterium praunsnitzii. Fecal microbiota transplantation in murine tumor models from HV treated with ATB alone reduced antitumor responses to anti-PD-1, while transplanted samples from HV treated with ATB+DAV132 circumvented resistance to anti-PD-1. This anti-tumor response in mice was associated with tumor microenvironment increased the ratio of total CD8+ T cells/ regulatory T cells, and three distinct activated CD8+ T cell population whiting the tumor within the tumor, as well as gene expression of interferon gamma (INFγ) in the mesenteric lymph nodes. In addition, a unique gene signature with downregulation of IL-6 and reactive oxygen pathways was found in the mice treated with FMT from ATB+DAV132 sample and treated with anti-PD-1. DAV132 represents a new strategy for overcoming ATB-related dysbiosis and further studies are warranted to evaluate its efficacy in cancer patients on ICI.
Published in
The DAV132 colon-targeted adsorbent does not interfere with plasma concentrations of antibiotics but prevents antibiotic-related dysbiosis: a randomized phase I trial in healthy volunteers
Messaoudene M, Ferreira S, Saint-Lu N et al. · Nature communications 2024 · PMID 39278946 · doi:10.1038/s41467-024-52373-8
This dataset
Open GSE251922 in finder → Find more mouse RNA-seq datasets →
Download · which file do I need?

Direct links to NCBI and ENA, no account and no request form. Pick by what you want to do: take the small processed table to look, the supplementary files to re-analyse, or the original raw data to start over.

1 · Just have a look

Processed table

The series matrix: one table of values per sample as the submitters processed it. The smallest download, and it opens in Excel or R. Start here to see what the data look like.

Series matrix ↓
2 · Re-analyse it

Supplementary files

The count tables and other files the authors uploaded. Take only the samples you need, or the whole study as GSE251922_RAW.tar (it can run to tens of gigabytes).

All supplementary files ↗ Whole study · RAW.tar ↓
3 · Start from the raw reads

Raw sequencing reads

The original FASTQ files, straight from the sequencer, held at ENA. Large, and you align them yourself, so only choose this if you need to re-process the study from scratch.

Raw reads on ENA ↗

What the files usually look like: For RNA-seq the counts are usually a table among the supplementary files (look for 'counts', 'expression', 'FPKM' or 'TPM' in the file name). The series matrix of a sequencing study is sometimes nearly empty.

Also filed as BioProject PRJNA1055928 and SRA study SRP479691. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 39278946) ↗
Study design
8 conditions, mostly with about 5 replicates each
FMT CZA + ISO_CD8 ×5 FMT CZA + anti-PD-1_CD8 ×5 FMT CZA + DAV132 + ISO_CD8 ×5 FMT CZA + DAV132 + anti-PD-1_CD8 ×5 FMT CZA + DAV132 + PD-1_T ×5 FMT CZA + PD-1_T ×5 FMT CZA + ISO_T ×5 FMT CZA + DAV132 + ISOTYPE_T ×4

Supports a between-group comparison across 39 samples.

How we read this: 8 replicated groups read from 39 sample titles; they account for 39 of them. These groups are guessed from the sample names, not taken from the paper, so check them against the sample list below before relying on them.

Samples in this study
Datasets on a similar topic

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