# Multi-omics characterization of HIV-associated changes in the gut microbiome and host mucosal immunity

> **NIH NIH R01** · MASSACHUSETTS GENERAL HOSPITAL · 2020 · $792,154

## Abstract

PROJECT SUMMARY
The human gut harbors an enormously diverse community of commensal microbes that has co-evolved with
humans to assist in critical host metabolic and immune functions. The impact of changes in the microbiome on
disease states as diverse as diabetes, obesity, immunodeficiency, and inflammatory bowel disease (IBD) is only
now being recognized. Human immunodeficiency virus (HIV) infection has profound effects on the intestinal
mucosal environment with a hallmark of infection being a rapid depletion of CD4+ T cells within gut associated
lymphoid tissue (GALT) and impairment of intestinal epithelial barrier function. Despite this, our understanding
of intestinal microbiota changes occurring with HIV infection and the potential effects of these changes on host
immunity and HIV disease progression remains incomplete, particularly in populations in sub-Saharan Africa,
where HIV disease burden is greatest. Our prior published work is one of only a few studies to examine HIV-
associated changes in the gut microbiome in sub-Saharan Africa. Limitations of published studies of HIV-
associated alterations in the gut microbiome include 1) the use of 16S rRNA gene sequencing to identify bacterial
taxa abundances but failure to resolve differences at the strain level, 2) lack of deep functional characterization
of bacterial communities, 3) characterization of HIV-infected populations in developed regions only, and 4) lack
of integration with mechanistic experiments. Our proposal addresses the limitations in the field by 1) using
comprehensive culturomic, metagenomic, metatranscriptomics, and metabolomic approaches to fully
characterize the gut microbiome at the strain level, 2) assessing its function, 3) integrating studies of a U.S.
population along with subjects from sub-Saharan Africa, where HIV burden is greatest and where it is known
that baseline gut microbiota differ significantly from those living in developed regions and 4) integrating these
analyses with mechanistic studies using in vitro and ex vivo models. Overall, the combination of unique, well-
characterized human samples analyzed with cutting-edge assays that combine computational and immunologic
approaches is highly innovative and will seek to identify bacterial strains, genes, and molecules that impact HIV
disease in the U.S. and sub-Saharan Africa. This work will additionally lead to the generation of a multi-‘omic
database that will serve as a resource for the field, including community access to data and bacterial strains
isolated from samples analyzed in this project.

## Key facts

- **NIH application ID:** 9998941
- **Project number:** 5R01DK120485-03
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Douglas Kwon
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $792,154
- **Award type:** 5
- **Project period:** 2018-09-14 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9998941

## Citation

> US National Institutes of Health, RePORTER application 9998941, Multi-omics characterization of HIV-associated changes in the gut microbiome and host mucosal immunity (5R01DK120485-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9998941. Licensed CC0.

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