Enhancing Mechanistic Research on Precision Probiotic Therapies (R33 Clinical Trial Optional)
Last verified by NonDilute: 2026-04-29. Official notice and agency instructions control.
If you have preliminary evidence linking patient biology to probiotic response variability, NIH will fund you to prove causality and build predictive models—with optional clinical validation.
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What this is
This R33 mechanism funds research advancing precision probiotic therapies by characterizing person-specific biological features that determine probiotic treatment success. Applicants must have preliminary data showing potential host factors (microbiome composition, genetics, immune markers, lifestyle) correlate with probiotic response, then conduct rigorous mechanistic studies in animal models or human subjects to establish causality and predictive value. The goal is solving the heterogeneity problem—why some people respond well to probiotics while others don't—through systems-level biology. This is a later-stage grant (R33), ideal for teams with foundational evidence seeking to validate mechanisms.
Who can apply
Broad eligibility including small businesses, nonprofits with or without 501(c)(3) status, universities, government entities, and tribal organizations. No geographic restriction. For-profit companies are eligible but primarily targeted at research-focused organizations with capacity for mechanistic studies.
Eligible applicant types
- Private institutions of higher education
- County governments
- Public and State controlled institutions of higher education
- Independent school districts
- Nonprofits having a 501(c)(3) status with the IRS, other than institutions of higher education
- Native American tribal organizations (other than Federally recognized tribal governments)
- Special district governments
- Small businesses
- City or township governments
- Native American tribal governments (Federally recognized)
- Nonprofits that do not have a 501(c)(3) status with the IRS, other than institutions of higher education
- State governments
- For profit organizations other than small businesses
- Others (see text field entitled "Additional Information on Eligibility" for clarification)
- Public housing authorities/Indian housing authorities
Full description — from the agency
The purpose of this notice of funding opportunity (NOFO) is to support highly innovative mechanistic research to accelerate precision probiotic interventions. Specifically, this NOFO solicits R33 applications that will characterize person-specific features affecting probiotic responses to identify subgroups of probiotic responders and to enhance probiotic clinical outcomes. The ultimate goal of this NOFO is to identify, understand, and develop strategies to address barriers in precision probiotic therapies to account for the heterogenicity in humans that causes inconsistent probiotic responses. This NOFO will support studies to assess the ability of the unique patterns of host biology (e.g., native microbiome, immune system, gender, diet, age, genetic background, lifestyle, and health history) that are correlated with probiotic usage to detect the improvement of probiotic responsiveness. Well-suited applications must offer rigorously designed mechanistic studies using relevant/innovative animal models or in human subjects. This NOFO is intended to support projects where potential host biological patterns that are correlated with probiotic usage have been identified, as demonstrated with supportive preliminary data, but require further mechanistic studies to test for their causality or predictability. Applicants pursuing early-stage research to identify host biological patterns that may affect probiotic health outcomes should consider the companion (R61/R33) NOFO PAR-AT-24-XXX (TEMP-25412).
Topics: precision probiotics · mechanistic research · host microbiome · probiotic response prediction · personalized medicine · clinical trial optional
Public-source funding discovery only. This summary is generated from public agency data and may be incomplete or stale. NonDilute is not affiliated with, endorsed by, or acting on behalf of any government agency. Official notices and agency instructions control. NonDilute does not determine eligibility, provide grant-writing advice, or guarantee funding.