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Profiling murine gut influence on peripheral tolerance

UID: 10780

Publisher(s): University of California San Diego Microbiome Initiative

Description
Summary from the ENA: "Antibiotic exposure early in life, and other practices impacting the vertical transmission and ordered assembly of a diverse and balanced gut microbiota, are associated with a higher risk of immunological and metabolic disorders such as asthma and allergy, autoimmunity, obesity, and susceptibility to opportunistic infections. Here, we use a model of perinatal exposure to the broad-spectrum antibiotic ampicillin to examine how the acquisition of a dysbiotic microbiota affects neonatal immune system development. We find that the resultant dysbiosis imprints in a manner that is irreversible after weaning, leading to specific and selective alteration of the colonic CD4+ T-cell compartment. In contrast, colonic granulocyte and myeloid lineages, and other mucosal T-cell compartments are unaffected. Amongst colonic CD4+ T-cells, we observe the most pronounced effects on neuropilin negative, Rorgt- and Foxp3-positive regulatory T-cells, which are largely absent in antibiotic-exposed mice even as they reach adulthood. Immunomagnetically isolated dendritic cells from antibioticexposed mice fail to support the generation of Foxp3+ Tregs from naïve T-cells ex vivo. The perinatally acquired dysbiotic microbiota predisposes to dysregulated effector T-cell responses to Citrobacter rodentium or ovalbumin challenge. The transfer of the antibiotic-impacted, but not healthy fecal microbiota into germ-free recipients recapitulates the selective loss of colonic neuropilin-negative, Rorgt- and Foxp3-positive Tregs. The combined data indicate that the early-life acquisition of a dysbiotic microbiota has detrimental effects on the diversity and microbial community composition of offspring that persist into adulthood, and predisposes to inappropriate T-cell responses that are linked to compromised immune tolerance."
Subject of Study
Mus musculus
Subject(s)
CD4-Positive T-Lymphocytes
Dysbiosis
Forkhead Transcription Factors
Microbiota
T-Lymphocytes, Regulatory
Access via ENA

16S rRNA Seq files from 377 samples
Accession #: PRJEB42154

Access Restrictions
Free to All
Access Instructions
Data is publicly available via the European Nucleotide Archive for download via ftp as FASTQ files.
Associated Publications
Zhang X, Borbet T, Fallegger A, et al. An antibiotic-impacted microbiota compromises the development of colonic regulatory T cells and predisposes to dysregulated immune responses. mBio. 2021; 12(1):e03335-20.
Data Type
Genomic
Equipment Used
Illumina MiSeq

The MiSeq is an integrated instrument that performs clonal amplification, genomic DNA sequencing, and data analysis with base calling, alignment, variant calling, and reporting in a single run.

Dataset Format(s)
FASTQ, gzip
Data Tool(s)
16S rRNA sequencing
Dataset Size
430 MB
Data Catalog Record Updated
2021-10-28