Enhancing Mechanistic Research on Precision Probiotic Therapies (R61/R33 Clinical Trial Optional)
🏛 National Institutes of Health (HHS-NIH11)
✓ Free, no account · Source: Grants.gov · Last verified Sep 7, 2026
Can you apply?
This grant is for researchers studying precision probiotic therapies and personalized responses. Eligible applicants include academic institutions, research organizations, nonprofits, and some government agencies. Foreign organizations cannot apply, though foreign components of U.S. organizations are permitted. All applicants must be able to conduct rigorous mechanistic research using observational data, animal models, or human subjects.
The R61/R33 is a phased mechanism. The R61 phase (up to 2 years) focuses on identifying host features linked to probiotic response heterogeneity. The R33 phase advances to mechanistic studies validating those patterns. Combined project duration cannot exceed 5 years.
Transition from R61 to R33 requires meeting specific milestones defined at application. Applicants must demonstrate capacity for high-quality research involving human or animal studies and data analysis.
Not the right fit? Find grants for your organization in 5 questions →
Program description
The purpose of this notice of funding opportunity (NOFO) is to support highly innovative mechanistic research to accelerate precision probiotic interventions using a milestone-driven, biphasic award mechanism, R61/R33 Phased Innovation Award. Specifically, this NOFO solicits 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.
The first phase, funded by the R61, will providing for up to 2 years to identify unique host biological patterns (e.g., native microbiome, immune system, gender, diet, age, genetic background, lifestyle, and health history) that are correlated with heterogeneity of probiotic clinical effects using observational or secondary data analysis studies. The second phase, funded under the R33, will support studies to assess the ability of the unique patterns determined in the R61 phase to detect the improvement of probiotic responsiveness in rigorously designed mechanistic studies in relevant animal models or in human subjects.
The combined R61/R33 should not exceed 5 years. Transition from the R61 to the R33 phase of the award will be administratively reviewed and will be determined based on successful completion of Transition Milestones that need to be clearly specified in the R61 phase application.
Support for a single phased award that does not need the R61 Exploratory phase is available in the companion (R33) NOFO, PAR-AT-24-XXX (TEMP-25413).
Who can apply
Eligible applicants
How to apply
Application links
Key dates & requirements
Required documents
- SF-424 (R&R) form
- Project Narrative (R61 and R33 phases clearly separated)
- Research Strategy with Specific Aims
- R61-to-R33 Transition Milestones
- Detailed Budget and Budget Narrative
- Biographical Sketches of Key Personnel
- Institutional Commitments and Facilities
Program contact
- 👤 National Institutes of Health
- 📧 grantsinfo@nih.gov
- 📞 301-402-2541
Funding track record
Recent awards under CFDA 93.393 from the last 3 years — real organizations that won funding through this same program.
Top 10 Largest Recent Awards
-
$213,206,023
-
$56,669,166
-
$56,551,552
-
$50,762,187
-
$42,878,192
-
$37,448,862
-
$29,324,004
-
$26,395,336
-
$24,427,436
-
$23,149,727
Top States by Funding
- MA 11 awards $398.0M
- CA 10 awards $231.0M
- MN 4 awards $106.8M
- NY 7 awards $100.9M
- TN 7 awards $97.7M
Source: USAspending.gov — federal spending transparency. Data covers last 3 years.
Funding history
Annual funding for this program — Federal obligations (CFDA 93.393). How funding has trended year over year.
| 2024 | $754,945,159 | |
| 2025 | $834,514,512 | |
| 2026 est. | $520,096,276 |
FAQ
Who can apply for this grant?
Academic institutions (including HBCUs and HSIs), research nonprofits, faith-based organizations, tribal institutions, and eligible federal agencies can apply. Foreign organizations cannot apply, though foreign collaborators within a U.S. organization are allowed.
What is the R61/R33 mechanism?
It's a two-phase award. R61 funds up to 2 years for exploratory mechanistic research identifying host patterns affecting probiotic response. R33 funds mechanistic studies validating those patterns in animal models or humans. Total project cannot exceed 5 years.
When is the deadline?
The deadline is June 2, 2027 (fixed deadline, not rolling).
What makes a competitive application?
Strong applications clearly define transition milestones from R61 to R33, propose innovative mechanistic approaches, and demonstrate feasibility in identifying and validating probiotic response markers.
What are typical award amounts and project durations?
Award amounts are not specified in this NOFO. R61 phase supports up to 2 years; combined R61/R33 duration is capped at 5 years total.
💡 Tips for applicants
- Clearly define measurable milestones for R61 completion before R33 transition in your application.
- Focus on host biological patterns (microbiome, immune response, genetics, diet, lifestyle) that explain probiotic response variability.
- Use rigorous research design: secondary data analysis for R61, mechanistic studies in animal models or humans for R33.
- Demonstrate expertise in microbiome research, clinical phenotyping, or personalized medicine approaches.
- Connect your mechanistic findings directly to improving clinical probiotic outcomes and addressing heterogeneity in human responses.
⚠️ Common mistakes
Vague or unrealistic transition milestones between R61 and R33 phases lead to rejection. Applications lacking mechanistic depth—treating probiotics as black boxes rather than investigating biological mechanisms—are less competitive. Inadequate plans for studying population heterogeneity miss the core goal.
Similar grants
- OPEN Enhancing Mechanistic Research on Precision Probiotic Therapies (R33 Clinical Trial Optional) — National Institutes of Health
- OPEN NCCIH Natural Product Early Phase Clinical Trial Phased Innovation Award (R61/R33 Clinical Trial Required) — National Institutes of Health
- OPEN NCCIH Natural Product Early Phase Clinical Trial Award (R33 Clinical Trial Required) — National Institutes of Health
- OPEN Clinical Characterization of Cancer Therapy-induced Adverse Sequelae and Mechanism-based Interventional Strategies (R01 Clinical Trial Optional) — National Institutes of Health
- OPEN Precision and Systems Biology to Uncover the Link Between Chronic and Infectious Diseases — National Institutes of Health