# CRS Microbiome: Multi-omic Integrative Longitudinal Experimental (CRS-MILE) study

> **NIH NIH R01** · INDIANA UNIVERSITY INDIANAPOLIS · 2024 · $631,117

## Abstract

SUMMARY: Chronic rhinosinusitis (CRS) is a highly prevalent disease that inflicts a severe quality-of-
life (QOL) impairment. QOL-measures have ranked CRS among severe ailments such as congestive heart
failure, chronic obstructive pulmonary disease, and end-stage renal disease. Its high prevalence, chronic
duration, and extensive antibiotic use, result in a large personal and societal burden that places it among
the top ten most costly medical conditions. Although often considered an infectious disease, many now view
CRS as a chronic inflammatory disorder where host-microbial interactions play a role. Current data
suggest that microbiota alterations (dysbiosis) exist in CRS, and that loss of protective organisms with
acquisition of pathogens may contribute to the refractory nature of the disease.
 Our long-term goal is to determine the functional role(s) of the sinus microbiome in health and disease,
and to translate these novel insights into the CRS management algorithm with new therapeutic
objectives and targets for intervention. Our central hypothesis is that dysbiosis in CRS promotes
chronic mucosal inflammation and compromises response to therapy. This hypothesis has been
formulated on the basis of publications and preliminary data produced in the applicants' laboratories and
clinical practice, and will be tested by pursuing three specific aims: 1) Evaluate the functional capacity of
microbiome alterations observed in CRS using an integrative multi-`omics approach; 2) Determine the
relationship between microbiome alterations and CRS disease severity and therapeutic outcomes in a
longitudinal multi-institutional human intervention study; 3) Determine how CRS-associated microbes alter
sinonasal mucosal core functions to drive disease chronicity, through in vitro experimentation.
 We will use innovative technologic and analytic approaches to examine sinus biospecimens and
health outcomes, seeking to transform current clinical and research understanding of the role of microbes
in CRS. This study moves beyond prior small, cross-sectional, observational human CRS microbiome
association studies by defining molecular, cellular, and immunological processes using a multi-`omics
approach. Our study is unique in its examination of both control and CRS subjects, longitudinal sampling from
an intervention study, well-defined clinical outcomes, and delineation of mechanisms of host-microbial
crosstalk in the airway. The proposed research is significant because it is expected to advance
understanding of how the microbiome, including specific microbial species, impacts mucosal immunity and
barrier function in CRS. Ultimately, such knowledge will change the current treatment paradigm in CRS,
decrease antibiotic overuse, and direct development of new therapeutic goals and treatment strategies for
CRS patients.

## Key facts

- **NIH application ID:** 10802637
- **Project number:** 1R01AI175239-01A1
- **Recipient organization:** INDIANA UNIVERSITY INDIANAPOLIS
- **Principal Investigator:** Daniel N Frank
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $631,117
- **Award type:** 1
- **Project period:** 2023-11-16 → 2028-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10802637

## Citation

> US National Institutes of Health, RePORTER application 10802637, CRS Microbiome: Multi-omic Integrative Longitudinal Experimental (CRS-MILE) study (1R01AI175239-01A1). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/10802637. Licensed CC0.

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