Impact of the Microbiome-Gut-Brain Axis on Alzheimer's Disease and Alzheimer's Disease-Related Dementias (R01 Clinical Trial Not Allowed) | PAR 22 211

Opportunity Information: Apply for PAR 22 211

The National Institutes of Health (NIH) is soliciting R01 grant applications under Funding Opportunity Number PAR-22-211, titled "Impact of the Microbiome-Gut-Brain Axis on Alzheimer's Disease and Alzheimer's Disease-Related Dementias (R01 Clinical Trial Not Allowed)." The opportunity supports discretionary health research (CFDA 93.853 and 93.866) focused on how the human microbiome, especially microbes associated with the alimentary canal (the gastrointestinal tract) and other endogenous microbial sources, may influence the development and course of Alzheimer's disease (AD) and Alzheimer's disease-related dementias (AD/ADRD). The intent is to strengthen the evidence base beyond broad associations by funding rigorous mechanistic and translational studies that clarify causal pathways and identify actionable targets.

A central theme of the announcement is the microbiome-gut-brain axis, meaning the interconnected signaling between microbial communities and the nervous system through immune, metabolic, endocrine, and neural routes. NIH highlights that, despite increasing recognition of the microbiome as an important contributor to overall health and many diseases, its specific role in AD/ADRD has not been adequately addressed. Applications are expected to go beyond descriptive microbiome profiling and instead examine how microbial changes interact with genetic and non-genetic molecular targets relevant to dementia biology. In practice, this means proposing experiments that can explain "how" and "why" microbiome features might affect disease initiation, progression, or modification, including pathways that link microbial metabolites, inflammation, immune responses, blood-brain barrier integrity, or protein aggregation and neurodegeneration processes.

The FOA emphasizes mechanistic research that tests potential interactions between the microbiome and established or emerging AD/ADRD risk factors. This can include studies that connect microbial composition or function with molecular targets influenced by genetics (such as risk alleles or gene expression programs) and non-genetic contributors (such as age-related immune shifts, lifestyle exposures, or comorbidities). The translational expectation is that successful projects will clarify clinical relevance, meaning the work should be designed so that findings plausibly map onto human disease, even if some experiments occur in model systems. Ultimately, NIH is signaling that the end goal is to enable better therapeutic interventions, whether by identifying microbial-derived molecules to target, host pathways influenced by microbes, or microbiome-informed strategies that could complement other AD/ADRD approaches.

This is an R01 mechanism, which generally supports substantial, hypothesis-driven research programs rather than small pilot projects. The announcement specifies "Clinical Trial Not Allowed," indicating the funded work should not include NIH-defined clinical trials that prospectively assign human participants to interventions to measure health outcomes. However, basic and translational research can still include human biospecimens, observational analyses, and other non-interventional clinical research components, as long as the study design does not meet the definition of a clinical trial. The posted award ceiling is listed as $500,000, and the original closing date in the provided record is 2022-10-05.

Eligibility is broad and includes many types of domestic and non-domestic organizations. Eligible applicants span state, county, city or township, and special district governments; independent school districts; public and state-controlled institutions of higher education; private institutions of higher education; federally recognized Native American tribal governments; tribal organizations other than federally recognized governments; public housing authorities and Indian housing authorities; nonprofit organizations with and without 501(c)(3) status (other than institutions of higher education); for-profit organizations other than small businesses; and small businesses. The FOA also explicitly notes additional eligible groups such as Alaska Native and Native Hawaiian Serving Institutions, Asian American Native American Pacific Islander Serving Institutions (AANAPISI), Hispanic-serving Institutions, Historically Black Colleges and Universities (HBCUs), Tribally Controlled Colleges and Universities (TCCUs), faith-based or community-based organizations, eligible federal agencies, regional organizations, non-U.S. entities (foreign organizations), and U.S. territories or possessions. This broad eligibility reflects NIH's interest in drawing expertise from diverse research environments and communities, which is especially relevant for microbiome research where geography, diet, and population differences can shape microbial exposures and health outcomes.

In short, PAR-22-211 is aimed at advancing a more precise, experimentally grounded understanding of how the microbiome influences AD/ADRD through the gut-brain axis, with an emphasis on mechanisms, interaction with genetic and molecular targets, and translational relevance that can inform future therapeutic development, while staying within the bounds of non-clinical-trial R01 research.

• The National Institutes of Health in the health sector is offering a public funding opportunity titled "Impact of the Microbiome-Gut-Brain Axis on Alzheimer's Disease and Alzheimer's Disease-Related Dementias (R01 Clinical Trial Not Allowed)" and is now available to receive applicants.
• Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 93.853, 93.866.
• This funding opportunity was created on 2022-07-05.
• Applicants must submit their applications by 2022-10-05. (Agency may still review applications by suitable applicants for the remaining/unused allocated funding in 2026.)
• Each selected applicant is eligible to receive up to $500,000.00 in funding.
• Eligible applicants include: State governments, County governments, City or township governments, Special district governments, Independent school districts, Public and State controlled institutions of higher education, Native American tribal governments (Federally recognized), Public housing authorities/Indian housing authorities, Native American tribal organizations (other than Federally recognized tribal governments), Nonprofits having a 501 (c) (3) status with the IRS, other than institutions of higher education, Nonprofits that do not have a 501 (c) (3) status with the IRS, other than institutions of higher education, Private institutions of higher education, For-profit organizations other than small businesses, Small businesses, Others.

Apply for PAR 22 211

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