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A single early-in-life macrolide course has lasting effects on murine microbial network topology and immunity

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Paper-Ruiz-2017

Source code from:
Ruiz VE, Battaglia T, Kurtz ZD, et al. A single early-in-life macrolide course has lasting effects on murine microbial network topology and immunity. Nature Communications. 2017;8:518. doi:10.1038/s41467-017-00531-6.

Abstract

Broad-spectrum antibiotics are frequently prescribed to children. Early childhood represents a dynamic period for the intestinal microbial ecosystem, which is readily shaped by environmental cues; antibiotic-induced disruption of this sensitive community may have long-lasting host consequences. Here we demonstrate that a single pulsed macrolide antibiotic treatment (PAT) course early in life is sufficient to lead to durable alterations to the murine intestinal microbiota, ileal gene expression, specific intestinal T-cell populations, and secretory IgA expression. A PAT-perturbed microbial community is necessary for host effects and sufficient to transfer delayed secretory IgA expression. Additionally, early-life antibiotic exposure has lasting and transferable effects on microbial community network topology. Our results indicate that a single early-life macrolide course can alter the microbiota and modulate host immune phenotypes that persist long after exposure has ceased.

Description

This repository is set up to reproduce the figures and analyses within the publication, Ruiz et al. It contains the necessary scripts and code usd to analyze the multi-omics datasets generated. It does not contain the raw sequencing data nor the scripts to process the data, but this information can be found with the Data Availability section within the publication. In addition, most to all of the figures were generated individually and then placed into a single figure, which is not included in this repository.

Structure Summary

The data is structured according the experiment. Within the each experiment folder, a subfolder of omics' dataset and scripts are organized to accomodate the various data that was generated and different analyses performed. Below is a treeview of the folder arrangement along with a short summary of each experiment. Each analysis is made up of shell scripts, but may include more reproducible formats (Rmarkdown, IPython Notebooks).

Experiment Description
PulsePAT The effect of a single or multiple pulsed antibiotic exposure in C57BL/6 mice.
TransPAT Transfer of tylosin-perturbed cecal contents in early life C57BL/6 wild-type mice.
GF-PAT The effect of early life antibiotic treatment in germ-free or SPF colonized C57BL/6 mice.
IgA-Seq 16S microbial composition of IgA-bound or IgA-unbound bacteria
── Paper-Ruiz-2017/
│   └── PulsePAT/
│     └── 16S_OTU/
│     └── IgA_concentration/
│     └── RNAseq/
│     └── Nanostring/
│
│   └── TransPAT/
│     └── 16S_OTU/
│     └── IgA_concentration/
│
│   └── GF-PAT/
│     └── 16S_OTU/
│     └── IgA_concentration/
│     └── Physiology/
│     └── Nanostring/
│
│   └── IgA-Seq/

Figure structure

Figure Location
Figure-1b PulsePAT/16S_OTU/
Figure-1c PulsePAT/16S_OTU/
Figure-1d PulsePAT/16S_OTU/
Figure-1e PulsePAT/16S_OTU/
--------------- --------------------------------------------------------------------------------
Figure-2a PulsePAT/Nanostring/
Figure-2d PulsePAT/IgA_concentration/
Figure-2e PulsePAT/IgA_concentration/
Figure-2f PulsePAT/RNAseq/
Figure-2g PulsePAT/RNAseq/
--------------- --------------------------------------------------------------------------------
Figure-3b GF-PAT/16S_OTU/
Figure-3c GF-PAT/16S_OTU/
Figure-3d GF-PAT/Physiology/
Figure-3e GF-PAT/IgA_concentration/
Figure-3f GF-PAT/Nanostring/
Figure-3g GF-PAT/Nanostring/
--------------- --------------------------------------------------------------------------------
Figure-4b TransPAT/IgA_concentration/
Figure-4d TransPAT/16S_OTU/
Figure-4e TransPAT/16S_OTU/
Figure-4f TransPAT/16S_OTU/

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A single early-in-life macrolide course has lasting effects on murine microbial network topology and immunity

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