# The microbiome and aging in Clostridioides difficile infection

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2022 · $735,042

## Abstract

ABSTRACT
The indigenous microbiota plays a critical role in the health of their host by contributing to an ecosystem (the
microbiome) that reflects a stable environment shaped by the host and the resident microbes. Normal resident
microbes contribute to homeostatic functions including fostering immune system maturation, protecting against
pathogen invasion and assisting digestion of food. Conversely, many age-associated conditions such as
cardiovascular disease, neurodegenerative diseases, cancer and diabetes have been associated with abnormal
host-microbe interactions. The ultimate goal of this work is to develop therapeutic strategies and tactics that
permit us to foster beneficial host-microbe interactions and improve disease outcomes in older adults. In order
to accomplish this goal, we need to understand how the microbiota changes over the lifespan of the individual
and how this alters host function. The specific objective of this proposal is to understand how age-related
changes in the microbiota alters susceptibility to outcomes of infection with the pathogen Clostridioides difficile.
C. difficile infection (CDI) following disruption of the gut microbiota due to antibiotic administration causes
significant morbidity and mortality. Elderly patients are more susceptible to CDI and are at increased risk of
developing disease-related complications following infection. We hypothesize that changes in the microbiota and
host related to aging underlie the increased susceptibility to CDI that contributes to worse outcome of infection
in older adults. We will test our hypothesis with 3 specific aims conducted in a robust animal model of CDI. 1)
Compare and contrast the structure and function of the microbiome over the age range of mice. 2) Determine
the role that the microbiome has on shaping host immune responses related to age using CDI as a model disease
condition. 3) Investigate the possibility of manipulating the host and the indigenous microbiota to alter health and
disease. In this proposal, we intend to perform detailed investigations on the effects of aging on the microbiome
and the outcome of C. difficile infection. We will leverage a murine model of CDI for these studies. The results
of these studies should provide important insights on the relationship between advancing age, the host and the
microbiota that could improve our ability to deal with CDI and other conditions that are influenced by the
microbiota over the lifespan.

## Key facts

- **NIH application ID:** 10442824
- **Project number:** 1R01AI162787-01A1
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** VINCENT B YOUNG
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $735,042
- **Award type:** 1
- **Project period:** 2022-05-01 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10442824

## Citation

> US National Institutes of Health, RePORTER application 10442824, The microbiome and aging in Clostridioides difficile infection (1R01AI162787-01A1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10442824. Licensed CC0.

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