Role of Gut Microbiome in Regulating Reproduction and Its Impact on Fertility Status in Women Living with and Without HIV (R01 - Clinical Trial Optional) | PA 18 838

Opportunity Information: Apply for PA 18 838

This National Institutes of Health (NIH) funding opportunity (PA 18-838) supports R01 research projects that examine how the gut microbiome influences women s reproductive function and fertility, with explicit interest in comparing women living with HIV and women without HIV. The central idea is that microbial communities in the gastrointestinal tract may help regulate key brain endocrine pathways that coordinate reproduction and metabolism, and that disruptions in these microbial signals could contribute to infertility, metabolic dysfunction, or both. While the announcement allows for clinical trials, they are optional, meaning applicants can propose mechanistic clinical studies, translational human research, animal or laboratory based studies, or combined approaches as long as the work directly advances understanding of microbiome driven regulation of reproduction and fertility related outcomes.

A major scientific focus is on the gut microbiome as a potential upstream regulator of the major neuroendocrine axes that shape reproductive physiology: the hypothalamic pituitary gonadal (HPG) axis, the hypothalamic pituitary adrenal (HPA) axis, and the hypothalamic pituitary thyroid (HPT) axis. In practical terms, the FOA is looking for studies that can clarify whether, how, and under what conditions microbial metabolites, inflammatory signals, immune activation, or other microbiome linked mechanisms influence hormone production, ovulatory function, ovarian biology, menstrual cycling, stress responses, thyroid function, and downstream fertility outcomes. The emphasis on these interconnected axes reflects the reality that reproduction does not operate in isolation; it is tightly integrated with energy balance, stress physiology, immune status, and endocrine signaling.

The opportunity also highlights the potential for the research to produce tangible clinical value in the form of diagnostic markers. Specifically, NIH signals interest in identifying "signature microbiomes" or microbiome associated biomarkers that could help predict or diagnose reproductive or metabolic failure. This can include microbial taxa patterns, functional pathway signatures, metabolomic profiles, inflammatory markers linked to microbial activity, or integrated multi omics signatures that correlate with infertility phenotypes or endocrine dysregulation. The long term implication is that microbiome based indicators might eventually help clinicians stratify risk, tailor fertility interventions, or monitor treatment responses, particularly in populations where fertility and metabolic complications are more prevalent.

Programmatically, the topic aligns with several areas within NIH s Fertility and Infertility Branch portfolios. The FOA is relevant to basic ovarian biology, fertility preservation, assisted reproductive technology, spermatogenesis and sperm function (even though the title centers on women, the broader fertility portfolio interest is noted), and development of therapeutic interventions for infertility. The announcement also points out cross cutting relevance to other NIH interests where microbiome effects could intersect with reproductive health, including maternal and pediatric infectious disease, pediatric growth and nutrition, and intellectual and developmental disabilities and brain disorders (IDDB). The inclusion of HIV in the title underscores a specific interest in understanding how chronic infection, immune activation, antiretroviral therapy, inflammation, or HIV associated metabolic changes might interact with the gut microbiome to influence endocrine pathways and fertility status, and how those mechanisms compare with women without HIV.

From an administrative standpoint, this is a discretionary NIH grant using the R01 mechanism, categorized under Health, Income Security and Social Services and associated with CFDA number 93.865. The listed award ceiling is $499,999, and the original closing date shown in the source information is 2021-09-07 (meaning the specific posting may be historical, but the summary describes what it funded and the type of work it sought). Because it is an R01, proposals are typically expected to be hypothesis driven, well powered or well justified in design, and capable of producing substantial, generalizable insight rather than only preliminary observations.

Eligibility is broad and includes many types of applicants: state, county, and local governments; special districts; independent school districts; public and state controlled and private institutions of higher education; federally recognized tribes and other tribal organizations; public housing authorities; nonprofits with or without 501(c)(3) status; for profit organizations (other than small businesses) and small businesses; and other eligible entities. The FOA also explicitly calls out additional eligible applicants such as Historically Black Colleges and Universities (HBCUs), Hispanic serving institutions, Tribally Controlled Colleges and Universities (TCCUs), Alaska Native and Native Hawaiian Serving Institutions, Asian American and Native American Pacific Islander Serving Institutions (AANAPISIs), faith based and community based organizations, U.S. territories or possessions, and even non U.S. entities (foreign organizations) and regional organizations. This breadth indicates NIH interest in attracting diverse investigators, institutions, and study populations, which is particularly relevant for microbiome research where geography, diet, environment, and social determinants can strongly shape microbial composition and health outcomes.

Overall, the grant opportunity is designed to move the field beyond simple correlation between gut bacteria and reproductive health by supporting rigorous research that explains mechanisms, maps microbiome endocrine interactions through the HPG, HPA, and HPT axes, and clarifies how these relationships relate to fertility status in women with and without HIV. The expected payoff is a stronger biological foundation for future diagnostics and interventions, including the possibility of microbiome informed strategies to address infertility, endocrine disturbances, obesity, metabolic syndrome, stress related disorders, and infection linked reproductive complications.

• The National Institutes of Health in the health, income security and social services sector is offering a public funding opportunity titled "Role of Gut Microbiome in Regulating Reproduction and Its Impact on Fertility Status in Women Living with and Without HIV (R01 - Clinical Trial Optional)" and is now available to receive applicants.
• Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 93.865.
• This funding opportunity was created on 2018-06-26.
• Applicants must submit their applications by 2021-09-07. (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 $499,999.00 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.

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