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Aging Microbiome, Immunosenescence, and risk of Multi-drug Resistant Organism Colonization and Infection in the Nursing Home

Award Number: R01AG075283
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 02/15/2023
PERIOD OF PERFORMANCE END DATE: 11/30/2027

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Aging Microbiome, Immunosenescence, and risk of Multi-drug Resistant Organism Colonization and Infection in the Nursing Home - ABSTRACT Multidrug resistant organisms (MDROs) are bacteria that have become resistant to more than one antimicrobial agent. Intestinal MDROs constitute a major threat to public health because they are increasingly difficult to treat and result in increased costs, morbidity, and mortality when they spread outside of the gut. Clostridium difficile shares many of the same characteristics as MDROs and along with MDROs has been labeled by the Centers for Disease Control and Prevention as a national priority. No group suffers more from these intestinal MDROs than nursing home residents. The perfect storm of a vulnerable group of frail older adults living in close communities, with increased morbidity and mortality from bacterial infections, and corresponding high rates of MDRO colonization emphasize the importance of the nursing home as a priority setting for studies to reduce MRDO burden. The intestinal microbiome may be a key factor as it influences both the likelihood of de novo colonization and whether colonization results in disease. In this proposal we will: 1) determine carriage rates of key MDROs in nursing homes communities using novel rapid strain-specific technology (molecular inversion probes); 2) assess the dissemination of pathogenic organisms; 3) determine in vivo/vitro how an aging microbiome can induce intestinal inflammation, thus promoting MDRO colonization; and 4) determining the extent to which both microbial dysbiosis and immunosenescence increases the risk of MDRO colonization, infection, and worsening frailty. We hypothesize that environmental and clinical factors (e.g., medication) characteristic of the NH settings contribute to and shape a dysbiotic microbiome that favors an increased risk of MDRO colonization. We further hypothesize the extent of microbial dysbiosis will be the major contributor of MDRO colonization, thus providing a novel target to combat pathogen prevalence within the NH environment. Specifically, in Aim 1 we will develop and implement a cultivation-free, high-throughput, low-cost approach to provide deep strain-level resolution of MDROs and accelerate epidemiological studies of infectious diseases. Further we will derive a microbiome-based predictive tool, the NH-MDI, to assess individual risk of MDRO colonization. Aim 2 will determine the mechanisms by which the microbiome can influence epithelial homeostasis, thus providing a colonic microenvironment supportive of MDRO colonization. Aim 3 will include analysis of stool and blood samples from a prospective nursing home cohort in order to determine the relative contribution of aging microbiome dysbiosis to markers of immunosenescence for increased risk of MDRO colonization as well as risk of worsening frailty. Further, we will determine the extent that dysbiosis and immunosenescence correlates with risk of future infection over 18 months of follow-up. Defining these crucial parameters will provide the basis for development of novel microbiome therapeutics aimed at the prevention of nursing home infections and promoting healthy aging. In doing so, we will further develop novel approaches to identify infectious organisms that will be superior to current diagnostic methods.


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 = $702,553 )
2026	2026	UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL	55 LAKE AVE N	WORCESTER	MA	01655	WORCESTER	USA	Aging Research	001	4	3/2/2026	NON-COMPETING CONTINUATION	$70,254
2026	2026	UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL	55 LAKE AVE N	WORCESTER	MA	01655	WORCESTER	USA	Aging Research	000	4	12/4/2025	NON-COMPETING CONTINUATION	$632,299
														Subtotal = $702,553

Issue Date FY: 2025 ( Subtotal = $688,007 )
2025	2025	UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL	55 LAKE AVE N	WORCESTER	MA	01655	WORCESTER	USA	Aging Research	001	3	7/23/2025	NON-COMPETING CONTINUATION	$56,163
2025	2025	UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL	55 LAKE AVE N	WORCESTER	MA	01655	WORCESTER	USA	Aging Research	000	3	12/3/2024	NON-COMPETING CONTINUATION	$631,844
														Subtotal = $688,007

Issue Date FY: 2024 ( Subtotal = $700,886 )
2024	2024	UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL	55 LAKE AVE N	WORCESTER	MA	01655	WORCESTER	USA	Aging Research	001	2	5/1/2024	NON-COMPETING CONTINUATION	$70,088
2024	2024	UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL	55 LAKE AVE N	WORCESTER	MA	01655	WORCESTER	USA	Aging Research	000	2	11/16/2023	NON-COMPETING CONTINUATION	$630,798
														Subtotal = $700,886

Issue Date FY: 2023 ( Subtotal = $718,183 )
2023	2023	UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL	55 LAKE AVE N	WORCESTER	MA	01655	WORCESTER	USA	Aging Research	001	1	2/24/2023	NEW	$16,699
2023	2023	UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL	55 LAKE AVE N	WORCESTER	MA	01655	WORCESTER	USA	Aging Research	000	1	2/6/2023	NEW	$701,484
														Subtotal = $718,183

Grand Total All Awards = $2,809,629

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Aging Microbiome, Immunosenescence, and risk of Multi-drug Resistant Organism Colonization and Infection in the Nursing Home

Award Number: R01AG075283

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 02/15/2023

PERIOD OF PERFORMANCE END DATE: 11/30/2027

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