Role of Gut Microbiome in Regulating Reproduction and Its Impact on Fertility Status in Women Living with and Without HIV (R21 Clinical Trial Optional) | PA 18 839

Opportunity Information: Apply for PA 18 839

The National Institutes of Health (NIH) announced this grant opportunity (Funding Opportunity Number PA-18-839) to support exploratory research on how the gut microbiome may influence female reproduction and fertility, including in women living with HIV and women without HIV. Using the R21 mechanism, the FOA is designed to encourage innovative, early-stage, and potentially high-impact projects that can generate foundational evidence about microbiome-driven pathways affecting reproductive function. Clinical trials are optional under this announcement, meaning applicants can propose either basic/mechanistic human studies, observational or translational research, or clinical research that may include an intervention, as long as it fits the R21 scope.

The core scientific focus is on understanding whether and how gut microbial communities regulate metabolism and reproductive biology, with particular attention to communication between the gut and key neuroendocrine systems in the brain. The FOA highlights three major hormonal regulatory pathways: the hypothalamic-pituitary-gonadal (HPG) axis, which governs reproductive hormones and ovarian function; the hypothalamic-pituitary-adrenal (HPA) axis, which mediates stress responses that can disrupt menstrual cycling and fertility; and the hypothalamic-pituitary-thyroid (HPT) axis, which influences energy balance and metabolic health and can indirectly affect reproductive capacity. The broader idea is that microbial metabolites, immune signaling, inflammation, and microbiome-related metabolic shifts may alter these axes in ways that contribute to subfertility or infertility, and that these effects may differ by HIV status due to immune activation, antiretroviral therapy effects, comorbid infections, and systemic inflammation.

A major expected payoff from funded work is the identification of diagnostic markers, sometimes described as "signature microbiomes," that correlate with reproductive or metabolic failure. In practical terms, that could mean characterizing patterns of gut bacteria, microbial gene functions, or microbial metabolites associated with outcomes such as disrupted ovulation, diminished ovarian reserve, irregular cycles, infertility, or adverse metabolic profiles that often track with reproductive dysfunction. The FOA also frames the microbiome as a potential upstream contributor to conditions that commonly intersect with fertility challenges, including obesity and metabolic syndrome, stress-related disorders, infection, and anxiety. Because these conditions are common and biologically intertwined with neuroendocrine regulation, the announcement encourages research that can connect microbial features to hormonal signaling, immune status, metabolic markers, and reproductive endpoints in a coherent mechanistic model.

Programmatically, the opportunity is relevant to several NICHD-related areas, especially those within the Fertility and Infertility Branch. Examples named in the FOA include basic ovarian biology, fertility preservation, assisted reproductive technology, spermatogenesis and sperm function, and therapeutic interventions for infertility, reflecting interest in microbiome impacts across the broader reproductive landscape even when the title emphasizes women. The announcement also signals alignment with interests in maternal and pediatric infectious disease and pediatric growth and nutrition, as well as related institutes and centers, because microbiome-driven effects on metabolism, immunity, and infection risk can span reproductive health and broader population health concerns, particularly in the context of HIV.

In terms of funding structure and eligibility, this is a discretionary NIH grant under CFDA 93.865, with an award ceiling listed at $200,000. A wide range of organizations may apply, including state and local governments, public and private institutions of higher education, nonprofit organizations (with or without 501(c)(3) status), for-profit organizations (other than small businesses), and small businesses, as well as tribal governments and tribal organizations. The FOA explicitly notes additional eligible applicants such as Historically Black Colleges and Universities (HBCUs), Hispanic-serving institutions, Alaska Native and Native Hawaiian serving institutions, AANAPISI institutions, tribally controlled colleges and universities (TCCUs), faith-based or community-based organizations, eligible federal agencies, U.S. territories or possessions, and non-U.S. entities and regional organizations. The source information lists an original closing date of September 7, 2021, and a creation date of June 26, 2018, which helps place the announcement in time for anyone checking whether the opportunity is active, reissued, or superseded by a newer NIH notice.

Overall, the FOA is essentially a call for creative, rigorous studies that clarify whether the gut microbiome is a meaningful regulator of reproductive endocrinology and fertility, how those effects interface with metabolic and stress systems, and whether HIV status changes the biology or the clinical implications. The long-term vision is to move from correlation to mechanism and, eventually, toward practical tools such as microbiome-based biomarkers for risk stratification and, potentially, microbiome-informed prevention or treatment strategies for reproductive and metabolic dysfunction.

• 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 (R21 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 $200,000.00 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.

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