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

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.Electronic supplementary materialThe online version of this article (10.1186/s40168-019-0664-z) contains supplementary material, which is available to authorized users.

Comparing Gut Microbiome in Mothers’ Own Breast Milk- and Formula-Fed Moderate-Late Preterm Infants

“…However, HMO serve as a metabolic substrate for specific bacteria in the infant gut (Engfer et al, 2000;Gnoth et al, 2000). L-fucose is one of the monomers of HMO and is very abundant in the human gut with several common human gut bacteria including Bifidobacterium, E. coli, and several species of Bacteroides known to utilize the L-fucose (Eagon, 1961;Pacheco et al, 2012;Bunesova et al, 2016;Westreich et al, 2019). Based on our results, we speculate that MBM infants had access to more L-fucose as an oligosaccharide than did formula infants, which could have selected for certain bacteria in the infant gut (Bode, 2009).…”

Prevalence of comorbidities and risk factors in spondyloarthritis: results of a cross-sectional study

“…Endoscopically inactive disease was not associated with complete normalisation of diarrhoea. 24 Diarrhoea, reflecting gut inflammation, 25 was a noteworthy symptom of IBD among patients with SpA.…”

Significance of fucose in intestinal health and disease

“…Similarly, administration of fucosylated oligosaccharides to mice deficient in IL‐22 signaling, which present low levels of ileal fucosylation, counters the proliferation of the damaging opportunistic E. faecalis (Pham et al., 2014). When intestinal fucosylation is increased during idiopathic chronic diarrhea (ICD) in macaques, an increase in fucosidase production by Bacteroides is also observed (Westreich et al., 2019). And organisms that do not produce fucosidases, such as Prevotella dentalis and Haemophilus influenzae , still show upregulation of their fucose permeases suggesting cross‐feeding occurs (Westreich et al., 2019).…”

“…When intestinal fucosylation is increased during idiopathic chronic diarrhea (ICD) in macaques, an increase in fucosidase production by Bacteroides is also observed (Westreich et al., 2019). And organisms that do not produce fucosidases, such as Prevotella dentalis and Haemophilus influenzae , still show upregulation of their fucose permeases suggesting cross‐feeding occurs (Westreich et al., 2019).…”

“…Fuc also serves as a receptor for adhesins aiding in colonization within the gastrointestinal tract as has been observed for the microbe H. pylori (Ishijima et al., 2011) and several common viruses including rotavirus and norovirus (Figure 2c; Azagra‐Boronat et al., 2018; Huang et al., 2005; Mallagaray et al., 2017; Maroni et al., 2015; Rockx et al., 2005). Expression of C. jejuni adhesins were also upregulated when macaques with ICD increase their intestinal fucosylation, suggesting a possible interaction between intestinal microbes and fucose (Westreich et al., 2019). It then follows that fucosylated HMOs mimicking these receptors could potentially act as decoys to inhibit adherence of viruses or bacteria (Figure 2a), including C. jejuni , during breastfeeding (Yu et al., 2013).…”