Microbial modulation of mucosal wound healing in the larynx

PROJECT ABSTRACT
Voice disorders are among the most common communication disorders and estimated to affect 3-9% of
Americans annually. These disorders are often associated with laryngeal inflammation secondary to epithelial
injuries following phonotrauma, surgical resection, radiation, and various infectious processes. Serious injury
can lead to disordered mucosal remodeling, scar formation, and a profound dysphonia. Bacterial dysbiosis, a
disturbance in the microbial community structure, is implicated in a variety of inflammatory disease etiologies in
mucosal systems, however, understanding of laryngeal microbiota and their protective mechanisms against
mucosal inflammation remains limited. To date, laryngeal microbiome studies have been limited to
characterization of microbial communities in disease states of the larynx. Research in regard to bacterial
contributions to the maintenance and regeneration of laryngeal mucosa is still lacking. The overall goal of this
work is to identify bacterial species associated with each stage of epithelial wound healing in the larynx and
define the role of laryngeal microbiota in modulation of epithelial regeneration through a longitudinal study
using a unique combination of gnotobiotic laryngeal model and naphthalene induced epithelial injury model.
Aim 1 will investigate the role of resident microbiota in the acute wound healing of laryngeal epithelium by
measuring the expression of inflammatory markers and barrier protection associated genes in the larynges of
naphthalene injected germ-free mice and gnotobiotic mice colonized with laryngeal microbiota. Aim 2 will
identify wound-associated bacterial species by delineating the longitudinal dynamics of bacterial compositions
at multiple timepoints through wound healing process. Gnotobiotic mice colonized with candidate bacterial
species will be assessed with and without antibiotics treatment to confirm their beneficial or pathogenic
influence that promotes or inhibits laryngeal wound healing. Our overarching hypothesis is that laryngeal
microbiota is a significant contributor to the healing of injured epithelium in the larynx. By clarifying the role of
resident microbiota in laryngeal wound repair process, completion of our specific aims will have a direct
significant impact on our current understanding of laryngology, bacteriology, and laryngeal immunology.
Results of this novel application will lead to new facets of understanding for host-microbiome interactions and
will ultimately be used to develop innovative prevention and treatment strategies for laryngeal diseases with
mucosal injury.

Grant Number: 5R21DC021012-03
NIH Institute/Center: NIH
Principal Investigator: Ran An