The mucosal-luminal interface: an ideal sample to study the mucosa-associated microbiota and the intestinal microbial biogeography.

BACKGROUND: Alterations in gastrointestinal microbial communities have been linked to human disease. Most studies use fecal samples as a proxy for the intestinal microbiota; however, the fecal microbiome is not fully representative of the mucosa-associated microbiota at the site of disease. While mucosal biopsies can be used instead, they often contain a high proportion of host DNA that can confound 16S ribosomal RNA (rRNA) gene sequencing studies. METHODS: To overcome these limitations, we sampled the mucosal-luminal interface (MLI) to study the mucosa-associated microbiota. We also employed a simple bioinformatics workflow to remove contaminants from 16S rRNA gene profiling results. RESULTS: Our results indicate that the microbial differences between individuals are greater than those between different microenvironments within the same individual. Moreover, biopsy samples frequently contained contaminants that could significantly impact biopsy profiling results. CONCLUSIONS: Our findings highlight the utility of collecting MLI aspirates to complement biopsies and stools for characterizing human microbial communities.

Butyrate's role in human health and the current progress towards its clinical application to treat gastrointestinal disease.

Butyrate is a key energy source for colonocytes and is produced by the gut microbiota through fermentation of dietary fiber. Butyrate is a histone deacetylase inhibitor and also signals through three G-protein coupled receptors. It is clear that butyrate has an important role in gastrointestinal health and that butyrate levels can impact both host and microbial functions that are intimately coupled with each other. Maintaining optimal butyrate levels improves gastrointestinal health in animal models by supporting colonocyte function, decreasing inflammation, maintaining the gut barrier, and promoting a healthy microbiome. Butyrate has also shown protective actions in the context of intestinal diseases such as inflammatory bowel disease, graft-versus-host disease of the gastrointestinal tract, and colon cancer, whereas lower levels of butyrate and/or the microbes which are responsible for producing this metabolite are associated with disease and poorer health outcomes. However, clinical efforts to increase butyrate levels in humans and reverse these negative outcomes have generated mixed results. This article discusses our current understanding of the molecular mechanisms of butyrate action with a focus on the gastrointestinal system, the links between host and microbial factors, and the efforts that are currently underway to apply the knowledge gained from the bench to bedside.

Characterization of gastrointestinal pathologies in the dystonia musculorum mouse model for hereditary sensory and autonomic neuropathy type VI.

BACKGROUND: Dystonia musculorum (Dstdt ) is a murine disease caused by recessive mutations in the dystonin (Dst) gene. Loss of dorsal root ganglion (DRG) sensory neurons, ataxia, and dystonic postures before death by postnatal day 18 (P18) is a hallmark feature. Recently we observed gas accumulation and discoloration in the small intestine and cecum in Dstdt mice by P15. The human disease resulting from dystonin loss-of-function, known as hereditary sensory and autonomic neuropathy type VI (HSAN-VI), has also been associated with gastrointestinal (GI) symptoms including chronic diarrhea and abdominal pain. As neuronal dystonin isoforms are expressed in the GI tract, we hypothesized that dystonin loss-of-function in Dstdt-27J enteric nervous system (ENS) neurons resulted in neurodegeneration associated with the GI abnormalities. METHODS: We characterized the nature of the GI abnormalities observed in Dstdt mice through histological analysis of the gut, assessing the ENS for signs of neurodegeneration, evaluation of GI motility and absorption, and by profiling the microbiome. KEY RESULTS: Though gut histology, ENS viability, and GI absorption were normal, slowed GI motility, thinning of the colon mucous layer, and reduced microbial richness/evenness were apparent in Dstdt-27J mice by P15. Parasympathetic GI input showed signs of neurodegeneration, while sympathetic did not. CONCLUSIONS & INFERENCES: Dstdt-27J GI defects are not linked to ENS neurodegeneration, but are likely a result of an imbalance in autonomic control over the gut. Further characterization of HSAN-VI patient GI symptoms is necessary to determine potential treatments targeting symptom relief.