# Micron-scale Spatial Metagenomic Mapping of Microbial Biogeography in the Gastrointestinal Tract

> **NIH NIH R01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2021 · $611,597

## Abstract

Recent efforts to characterize the gut microbiome have significantly increased our knowledge of the composition
and abundance of host-associated bacteria communities in healthy and diseased states. However, translation
of these results into clinically informative therapeutics has been slow. Beyond antibiotic strategies, fecal
microbiota transplantation is the only other clinically validated approach to restore microbiome health. A key
roadblock has been the lack of detailed mechanistic understanding for how gut microbiota colonize the
gastrointestinal tract and specific factors that enable their success. Detailed understanding of local microbial
biogeography are not available, leading to inference of contribution of microbiota on health only from bulk-
averaged datasets. Delineating the precise spatial distribution and heterogeneity of microbiota at a micron-scale
and their specific association with host-specific cell types may lead to improved understanding of their role in
gastrointestinal health and disease. This proposal aims to develop a new approach through “spatial
metagenomics” to map the micron-scale microbial biogeography along the gastrointestinal tract and apply the
system for understanding gut microbiota colonization in a murine model. We hypothesize that the healthy gut
microbiota are organized in defined spatial patterns at the micron-scale along the gastrointestinal tract that reflect
an underlying robust and homeostatic network of inter-microbial and host-microbial interactions, which is
disrupted by specific environmental exposures and host factors that lead to dysbiosis and diseased states. We
will first generate cell particles that encapsulate groups of microbiota cells in their native co-association states
for high-throughput profiling by next-generation sequencing. Deconvolution of the data results in co-localization
networks that inform the spatial architecture of the population in their native habitat. We will characterize how
the microbiome biogeography changes along different parts of the murine gastrointestinal tract and their
responses to dietary changes in healthy states. Then, we will probe these spatial changes upon exposure to
various antibiotics that may selectively or broadly disrupt the underlying microbiota interaction network. These
disrupted communities will then be subjected to fecal microbiota transplantation, and the effects of such
recolonization on the establishment of new spatial microbiota architectures will be explored. Concurrently, we
will develop metabolic and network-based models to analyze the detailed mechanisms that underlie microbial
spatial architectures in the gastrointestinal tract under these healthy and disrupted states. If successful, this
project will demonstrate for the first time the spatial organization of the gut microbiota in health and disrupted
states using an unbiased and high-throughput method and generate key datasets and insights into the microbial
distribution along the gast...

## Key facts

- **NIH application ID:** 10186685
- **Project number:** 5R01AI132403-05
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Harris H Wang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $611,597
- **Award type:** 5
- **Project period:** 2017-06-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10186685

## Citation

> US National Institutes of Health, RePORTER application 10186685, Micron-scale Spatial Metagenomic Mapping of Microbial Biogeography in the Gastrointestinal Tract (5R01AI132403-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10186685. Licensed CC0.

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