# Aging and Clostridium difficile infection: interplay of microbiota and host response

> **NIH NIH K08** · UNIVERSITY OF VIRGINIA · 2021 · $160,157

## Abstract

PROJECT SUMMARY/ABSTRACT
Significance: Clostridium difficile is the most common pathogen to cause healthcare-associated infections and
has led to diarrheal diseases being the only cause of infectious diseases mortality in the United States to increase
from 2000 to 2014. Not only are adults aged 65 or older more likely to be infected, they make up 90% of deaths
from C. difficile infection (CDI). Research to look into mechanisms that increase the risk of deaths and severe
outcome from CDI in the aged host is now more important than ever.
Approach: Our preliminary studies show that aged mice have lower early innate immune responses and higher
mortality from CDI, but these differences in mortality and immune responses with aging can be overcome by
fecal microbiota transplant from young to aged mice. Using a novel aged mouse model of CDI we have
developed, I will identify factors that mediate the protection in aged mice on the intestinal
microbiome/metabolome side (Aim 1) and on the host response side (Aim 2). Aim 1 will analyze the microbiome
and metabolome to identify protective bacteria and metabolites to test for protection against CDI in aged mice.
Aim 2 will utilize RNA sequencing and flow cytometry to identify immune cells and pathways that mediate the
microbiome effect on host response and test them by reversing the pathway during fecal transplant experiment.
Combining findings from both aims will allow us to more completely characterize the pathogenesis and find
targets for developing novel therapeutics.
Career development: This proposal leverages the institutional commitment and training environment at
University of Virginia, resources of the Warren/Guerrant Lab, mentorship from world experts on C. difficile and
mucosal immunology, and expert collaborations in the field of bioinformatics. My career development plan
includes structured oversight and guidance from my mentorship team, targeted coursework to acquire novel
skills in key areas of the project (immunology, bioinformatics), focused workshops to enhance faculty
development skills, publication benchmarks and plans to apply for independent funding, all of which will help
establish me as an independent investigator in the field of infections in the aging host.

## Key facts

- **NIH application ID:** 10147632
- **Project number:** 5K08AG064151-03
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** Jae Hyun Shin
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $160,157
- **Award type:** 5
- **Project period:** 2019-07-15 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10147632

## Citation

> US National Institutes of Health, RePORTER application 10147632, Aging and Clostridium difficile infection: interplay of microbiota and host response (5K08AG064151-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10147632. Licensed CC0.

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