Mapping Gut Microbiota Composition In Situ Using High-Resolution Spatial Microdissection Technique
Abstract
The most prominent diseases of modern times, including inflammatory bowel diseases (IBD) such as Crohn’s disease and ulcerative colitis, colon cancer, and metabolic diseases, such as diabetes and obesity, are caused as a result of failure to maintain homeostatic interactions with commensal bacteria. However, at the moment we do not fully understand the mechanisms that regulate host-microbe interactions. Moreover, attempts to identify common microbiome-associated patterns linked with these diseases have either failed or are inconsistent at best. It is likely that the intestinal flora is spatially stratified just like any other ecosystem, and so far large-scale sequence analysis of intestinal microbiota that uses fecal biota or entire intestinal luminal content as a surrogate for looking at gut microflora has failed to pick up transverse stratification of intestinal microbiome. We propose a novel approach for determining the structural and functional stratification of intestinal microbiome. To do this, we will first use a combination of high-resolution microbial capture system along with massively parallel sequencing techniques to delineate niche bacterial communities in a structurally intact intestinal lumen. We will further assess the role of host immunity in organizing and building resilience of bacterial communities within the gut lumen. We will apply these approaches to understand how common genetic factors that are associated with IBD influence the function and structure of microbiota to cause dysbiosis and chronic inflammation.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1810281
Entities
People
- Shipra Vaishnava
Organizations
- Brown University
- United States Army