The Metatranscriptome of the Rhesus Macaque: Investigating Potential Causes of Idiopathic Chronic Diarrhea

Abstract

The study of the gut microbiome—the collection of microbes within the intestinal tract and the genes they express—is growing in popularity as associations are found between diet, gut microbiome activity, and host health and disease. However, current metagenomic and ribosomal profiling approaches are unable to capture changes in activity within microbiome populations. In this environment, shifts in diet may not result in microbiome population changes, but may instead influence the activity of the existing microbial community. Metatranscriptomics, the study of microbial population activity based on RNA‐seq data, offers detailed data on the gene expression of all microbes within the sampled community. We have created a new bioinformatics pipeline, SAMSA (Simple Analysis of Metatranscriptome Sequence Annotations), designed specifically for metatranscriptome dataset analysis, with options for either in‐house or external server‐based computational processing. Designed for use by researchers with relatively little bioinformatics experience, SAMSA offers a breakdown of metatranscriptome activity by organism or transcript function, and is fully open source.We have applied SAMSA to examination of Idiopathic Chronic Diarrhea (ICD), a long‐term inflammatory bowel condition in rhesus macaques that leads to significant mortality in captive populations. Previous studies on ICD have failed to identify a causative pathogen, and the disease is believed to be the result of a wider shift in the microbiome across multiple taxa. Through metatranscriptomic examination of both organism and functional activity shifts, we have identified underlying shifts in the gut environment of ICD‐afflicted animals, and observed changes in the activity of affected microbial communities. These results will offer new approaches for not simply providing palliative treatment for these affected animals, but permanently eliminating the ICD condition from captive rhesus macaque communities. These results demonstrate the value of a metatranscriptome‐based approach for studying microbiome environments.Support or Funding InformationFunding provided by Signature Research in Genomics award.