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Interactions between resident microbiota and invading middle ear pathogens

Award Number: R01DC023205
ORGANIZATION: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/2026
PERIOD OF PERFORMANCE END DATE: 06/30/2031

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Interactions between resident microbiota and invading middle ear pathogens - SUMMARY Acute infections of the middle ears (Acute Otitis Media, AOM) are a widespread problem and a leading cause of antibiotic (over) use and ambulatory surgeries in children globally, including in the United States. The reason(s) why large numbers of infants are prone to recurrent bacterial ear infections is not fully understood, but there is growing evidence of a central role of the resident microbiota of the nasopharynx in mediating susceptibility/resistance to AOM. Human and animal studies show that the respiratory microbiota of healthy adults is relatively stable and can confers protection against colonization and invasion by pathogens of the middle ear (ME). However, in neonates/infants/children the microbiota can be much more dynamic and changing, and can more easily be disrupted by antibiotics (dysbiosis). Thus the most common treatment for AOM, antibiotics, could potentially destabilize the child's microbiota, disrupting the resistance it can confer and making the child more susceptible to subsequent, potentially repeated AOM. Although this string of arguments is fairly well accepted, there is a substantial knowledge gap in our understanding of how resident microbes protect against respiratory and otopathogens, and how antibiotic- induced disruption of the respiratory microbiota might cause susceptibility to colonization and pathogenesis, increasing AOM. We hypothesize that infants are more sensitive to respiratory and otopathogens because they lack a stable microbiota that can confer resistance. We will test this in two complementary ways. We will use topical antibiotics to locally disrupt the resident microbiota, inducing a state of dysbiosis within the respiratory tract. Our new preliminary data demonstrate that such treatment can substantially increase susceptibility to respiratory and middle ear (ME) pathogens. Here we will define this effect and measure how it differs in neonates, adolescents and adults, which differ substantially in the makeup and stability of microbiota. We will follow a highly complementary approach that takes advantage of our recent work establishing a nasopharyngeal consortium of commensals (NPCC) composed of microorganisms that correlate with health (lack of AOM) in a large cohort of children. Our exciting preliminary data in experimental infections in mice now demonstrate that this NPCC can successfully colonize/persist and confer substantial resistance to respiratory and otopathogens in mice. We will now define the resistance conferred in neonates, adolescent and adult mice. These in vivo experiments will identify specific interbacterial interactions that confer resistance to AOM, and can guide the use of in vitro experiments in air-liquid interface (ALI) conditions that closely mimic the mammalian respiratory tract, that will define the mechanisms involved. This work will substantially guide more enlightened approaches to reduce the incidence of AOM and the antibiotic-induced dysbiosis that has the potential to contribute to long term health problems for many children.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $660,846 )
2026	2026	UNIVERSITY OF GEORGIA RESEARCH FOUNDATION, INC.	310 E CAMPUS RD RM 409	ATHENS	GA	30602	CLARKE	USA	Research Related to Deafness and Communication Disorders	000	1	9/1/2026	NEW	$660,846
														Subtotal = $660,846

Grand Total All Awards = $660,846

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Interactions between resident microbiota and invading middle ear pathogens

Award Number: R01DC023205

ORGANIZATION: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/01/2026

PERIOD OF PERFORMANCE END DATE: 06/30/2031

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