Understanding the role of Gut Immune dysfunction and Gut Microbiome in pathogenesis of Central Nervous System co-morbidities in people living with HIV (R21 Clinical Trial Not Allowed) | RFA MH 22 230

Opportunity Information: Apply for RFA MH 22 230

The National Institutes of Health (NIH) is offering a discretionary grant opportunity (Funding Opportunity Number RFA-MH-22-230; CFDA 93.242) titled "Understanding the role of Gut Immune dysfunction and Gut Microbiome in pathogenesis of Central Nervous System co-morbidities in people living with HIV (R21 Clinical Trial Not Allowed)." It is an R21 mechanism, which is typically used to support exploratory, early-stage, or high-impact projects that generate foundational data, test novel ideas, or open up new lines of investigation rather than fund large, definitive programs. A key boundary of this announcement is that clinical trials are not allowed, meaning applicants should not propose studies designed to prospectively assign human participants to interventions in order to evaluate health-related outcomes. Human-focused clinical research may still be possible if it stays within non-trial parameters, such as observational or mechanistic work, but proposals must be framed carefully to remain compliant with the "clinical trial not allowed" requirement.

The scientific focus is the gut-brain axis in the context of HIV, specifically how HIV-associated changes in gut microbiota and gut immune function contribute to central nervous system (CNS) comorbidities and mental health outcomes in people living with HIV. The initiative is aimed at uncovering mechanisms, not just correlations. In practice, that means research that can explain how HIV infection and/or antiretroviral therapy (ART) disrupts the gut microbial community and gut mucosal immunity, how those disruptions affect immune signaling and inflammation, and how downstream pathways influence brain biology. The announcement explicitly highlights brain functions, neural circuits, neurotransmitters, signaling pathways, and synaptic plasticity as areas of interest. In other words, NIH is looking for projects that connect gut immune dysfunction and microbiome alterations to concrete neurobiological changes that could plausibly drive or worsen outcomes such as depression, anxiety, cognitive impairment, or other CNS-related comorbidities that occur alongside HIV.

This opportunity supports both basic and clinical mechanistic studies, as long as they align with the non-clinical-trial constraint. Basic studies might include work in model systems that can isolate causal pathways linking microbiome shifts or gut immune activation to neural and behavioral phenotypes relevant to HIV. Clinical mechanistic studies might involve profiling and integrative analyses in people living with HIV that examine microbiome composition and function, markers of gut barrier integrity, immune activation and inflammatory mediators, and neurocognitive or neuropsychiatric measures, with an emphasis on identifying biological pathways that connect these domains. The intent is to move beyond describing that changes exist, and instead clarify how those changes propagate through immune and metabolic routes to alter CNS signaling and plasticity, including in the setting of ART exposure.

A wide range of applicants are eligible, reflecting an intent to attract proposals from universities, medical centers, community-oriented organizations, and other research-capable entities. Eligible applicants include state, county, city, 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; Native American tribal organizations that are not federally recognized; public housing authorities and Indian housing authorities; nonprofits with and without 501(c)(3) status (excluding institutions of higher education); for-profit organizations other than small businesses; small businesses; and other organizations. The announcement also calls out additional eligible groups such as Alaska Native and Native Hawaiian Serving Institutions, Asian American Native American Pacific Islander Serving Institutions (AANAPISISs), 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, U.S. territories or possessions, and even non-U.S. entities (foreign organizations). This broad eligibility suggests NIH is open to interdisciplinary teams and diverse institutional settings, including those with strong community connections or specialized populations.

Administratively, the opportunity was created on April 25, 2022, with an original closing date of November 18, 2022. While the listing does not provide an award ceiling or expected number of awards in the excerpt, the R21 format typically implies smaller, time-limited exploratory budgets compared to larger R-series grants, and applicants generally need to craft sharply focused aims that can be accomplished within that scope. Overall, the program is designed to accelerate mechanistic understanding of how HIV and ART-related disruptions in the gut microbiome and gut immune environment may shape CNS biology and mental health, with the long-term implication that clearer mechanisms could point to future targets for prevention or treatment strategies (even though intervention trials themselves are not part of this specific funding call).

• The National Institutes of Health in the health sector is offering a public funding opportunity titled "Understanding the role of Gut Immune dysfunction and Gut Microbiome in pathogenesis of Central Nervous System co-morbidities in people living with HIV (R21 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): 93.242.
• This funding opportunity was created on 2022-04-25.
• Applicants must submit their applications by 2022-11-18. (Agency may still review applications by suitable applicants for the remaining/unused allocated funding in 2026.)
• 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 RFA MH 22 230

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