Thursday, September 18, 2025 9/18/2025

Microbiome-gut-brain dysfunction in prodromal and symptomatic Lewy body diseases

Award Number: R01NS133569
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/01/2023
PERIOD OF PERFORMANCE END DATE: 07/31/2028

Group Awards By:

View Award Description

Microbiome-gut-brain dysfunction in prodromal and symptomatic Lewy body diseases - PROJECT SUMMARY/ABSTRACT Cognitive decline in Lewy body dementias [Parkinson’s Disease Dementia (PDD) and Dementia with Lewy Bodies (DLB); a category of Alzheimer’s disease and related dementias (ADRD)], causes significant functional impairment and does not respond well to existing treatments. Perhaps the greatest challenge for developing effective treatments is the lack of a mechanistic understanding of the key events driving pathophysiology. Increasing evidence suggests that a perturbed gut microbiome (dysbiosis) driven by a bloom in sulfate reducing bacteria and increased intestinal permeability may be key mechanisms driving disease pathogenesis in Lewy body diseases. There is a need to evaluate whether these factors are present early in the disease course and associated with known disease processes, such as midbrain degeneration and clinical outcomes. Idiopathic REM Sleep behavior disorder (iRBD), is one of the earliest and most specific prodromal indicators of Lewy body diseases as up to 96.6% of iRBD patients will progress to an alpha-synucleinopathy at 14 years follow up. This population therefore provides an opportunity to conduct a novel evaluation of the presence of a bloom in SRB/dysbiosis and increased intestinal permeability early in the disease and whether these mechanisms are associated with known disease processes (increases in α-synuclein, midbrain degeneration and clinical outcomes). The proposed project will conduct a prospective, cross-sectional study to test the hypothesis that abnormal lactulose breath tests with elevated H2S concentration (as a marker of dysbiosis and a bloom of SRB in the gut) are present at prodromal stages of the disease and associated with increases in markers of increased intestinal permeability and microbial translocation of lipopolysaccharide (total bacterial 16S rRNA gene and lipopolysaccharide binding protein; LBP), known disease processes (plasma concentration of α-synuclein, MRI biomarkers of integrity of SNc and LC) and clinical outcomes. We will recruit prodromal (iRBD), symptomatic Lewy body disease patients (PD and DLB) and HC to evaluate our hypotheses. Consistent with several objectives outlined in PAR-22-211, the completion of the proposed project will advance our mechanistic understanding of the effects of a boom in SRB/dysbiosis, potentially identifying targets for disease modifying treatments. Should our results determine an important role of gut SRB bloom/dysbiosis in the pathophysiology of Lewy body diseases, these measurements could be incorporated into routine clinical practice to screen for emerging pathogenic processes. Notably, many potential treatments targeting the microbiome are readily available and subsequent clinical trials can evaluate whether interventions targeting a bloom in SRB/dysbiosis could be used to intervene before overt motor and cognitive symptoms develop.


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: 2025 ( Subtotal = $889,363 )
2025	2025	LOVELACE BIOMEDICAL RESEARCH INSTITUTE	2425 RIDGECREST DR SE	ALBUQUERQUE	NM	87108	BERNALILLO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	7/22/2025	NON-COMPETING CONTINUATION	$889,363
														Subtotal = $889,363

Issue Date FY: 2024 ( Subtotal = $932,250 )
2024	2024	LOVELACE BIOMEDICAL RESEARCH INSTITUTE	2425 RIDGECREST DR SE	ALBUQUERQUE	NM	87108	BERNALILLO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	2/16/2024	SUPPLEMENT FOR EXPANSION	$42,140
2024	2024	LOVELACE BIOMEDICAL RESEARCH INSTITUTE	2425 RIDGECREST DR SE	ALBUQUERQUE	NM	87108	BERNALILLO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	2	8/1/2024	NON-COMPETING CONTINUATION	$890,110
														Subtotal = $932,250

Issue Date FY: 2023 ( Subtotal = $815,866 )
2023	2023	LOVELACE BIOMEDICAL RESEARCH INSTITUTE	2425 RIDGECREST DR SE	ALBUQUERQUE	NM	87108	BERNALILLO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	7/28/2023	NEW	$815,866
														Subtotal = $815,866

Grand Total All Awards = $2,637,479

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Microbiome-gut-brain dysfunction in prodromal and symptomatic Lewy body diseases

Award Number: R01NS133569

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 08/01/2023

PERIOD OF PERFORMANCE END DATE: 07/31/2028

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer