Fecal metatranscriptomics of macaques with idiopathic chronic diarrhea reveals altered mucin degradation and fucose utilization

Samuel T Westreich,Mary E Kable,Danielle G Lemay,Amir Ardeshir,Zeynep Alkan,Ian Korf

doi:10.1186/s40168-019-0664-z

Samuel T Westreich, Mary E Kable + Show 4 more

Open Access

https://doi.org/10.1186/s40168-019-0664-z

Copy DOI

Abstract

BackgroundIdiopathic chronic diarrhea (ICD) is a common cause of morbidity and mortality among juvenile rhesus macaques. Characterized by chronic inflammation of the colon and repeated bouts of diarrhea, ICD is largely unresponsive to medical interventions, including corticosteroid, antiparasitic, and antibiotic treatments. Although ICD is accompanied by large disruptions in the composition of the commensal gut microbiome, no single pathogen has been concretely identified as responsible for the onset and continuation of the disease.ResultsFecal samples were collected from 12 ICD-diagnosed macaques and 12 age- and sex-matched controls. RNA was extracted for metatranscriptomic analysis of organisms and functional annotations associated with the gut microbiome. Bacterial, fungal, archaeal, protozoan, and macaque (host) transcripts were simultaneously assessed. ICD-afflicted animals were characterized by increased expression of host-derived genes involved in inflammation and increased transcripts from bacterial pathogens such as Campylobacter and Helicobacter and the protozoan Trichomonas. Transcripts associated with known mucin-degrading organisms and mucin-degrading enzymes were elevated in the fecal microbiomes of ICD-afflicted animals. Assessment of colon sections using immunohistochemistry and of the host transcriptome suggests differential fucosylation of mucins between control and ICD-afflicted animals. Interrogation of the metatranscriptome for fucose utilization genes reveals possible mechanisms by which opportunists persist in ICD. Bacteroides sp. potentially cross-fed fucose to Haemophilus whereas Campylobacter expressed a mucosa-associated transcriptome with increased expression of adherence genes.ConclusionsThe simultaneous profiling of bacterial, fungal, archaeal, protozoan, and macaque transcripts from stool samples reveals that ICD of rhesus macaques is associated with increased gene expression by pathogens, increased mucin degradation, and altered fucose utilization. The data suggest that the ICD-afflicted host produces fucosylated mucins that are leveraged by potentially pathogenic microbes as a carbon source or as adhesion sites.

Highlights

Idiopathic chronic diarrhea (ICD) is a common cause of morbidity and mortality among juvenile rhesus macaques
Transcripts from mucin-degrading bacteria and mucindegrading enzymes were increased in ICD Having screened the metatranscriptomes for potential pathogens, we investigated our hypothesis that ICD is associated with increased mucin degradation
Mucin foraging is a primary feature in the colon; our findings of increased gene expression by mucin-degrading bacteria, increased expression of mucin-degrading enzymes, increased expression of mucin and fucosylation by host cells, and increased fucose utilization by specific bacteria suggest these strong signals of the metatranscriptome in ICD do not arise purely from the proximal intestine

Summary

Introduction

Idiopathic chronic diarrhea (ICD) is a common cause of morbidity and mortality among juvenile rhesus macaques. Captive macaque juveniles often develop idiopathic chronic diarrhea (ICD), characterized by repeated episodes of intestinal distress and intestinal inflammation, and lack the presence of known intestinal pathogens detectable by culture-based methods [2, 3]. Prior work demonstrated that microbial diversity is decreased in macaques with colitis [7] and that therapeutic helminth infection ameliorates the clinical symptoms of ICD that are associated with the restoration of microbial diversity [3]. It is not yet known which features of a microbiome, beyond diversity, are protective against ICD

Methods

Results

Discussion

Conclusion