Enhancing Mechanistic Research on Precision Probiotic Therapies (R33 Clinical Trial Optional)
Can you apply?
This grant is for research institutions and organizations working on mechanistic studies of precision probiotic therapies. Eligible applicants include universities, HBCUs, Hispanic-serving institutions, tribal colleges, faith-based organizations, nonprofits, and federal agencies. Domestic U.S. entities and their domestic components are eligible; foreign organizations are not. The grant supports R33 applications with preliminary data demonstrating host biological patterns affecting probiotic responses, requiring further mechanistic validation through rigorous studies in animal models or humans.
Research must characterize person-specific features influencing probiotic efficacy and identify responder subgroups. The focus is on understanding how factors like microbiome, immune function, genetics, diet, age, and lifestyle affect probiotic outcomes. Studies should be well-designed mechanistic investigations building on established preliminary findings.
This grant is for research institutions and organizations working on mechanistic studies of precision probiotic therapies. Eligible applicants include universities, HBCUs, Hispanic-serving institutions, tribal colleges, faith-based organizations, nonprofits, and federal agencies. Domestic U.S. entities and their domestic components are eligible; foreign organizations are not. The grant supports R33 applications with preliminary data demonstrating host biological patterns affecting probiotic responses, requiring further mechanistic validation through rigorous studies in animal models or humans.
Research must characterize person-specific features influencing probiotic efficacy and identify responder subgroups. The focus is on understanding how factors like microbiome, immune function, genetics, diet, age, and lifestyle affect probiotic outcomes. Studies should be well-designed mechanistic investigations building on established preliminary findings.
Program description
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).
Who can apply
Eligible applicants
- 501(c)(3) Public Charity
- City / Municipal Government
- County Government
- Faith-based Organization
- Nonprofits
- Private University
- Public Authority
- Public K-12 School
- Public University
- Researcher (independent)
- Small Business (SBA-defined)
- Special District
- State Government
- Tribal Nation
- Tribal Organization
Details
This grant is for research institutions and organizations working on mechanistic studies of precision probiotic therapies. Eligible applicants include universities, HBCUs, Hispanic-serving institutions, tribal colleges, faith-based organizations, nonprofits, and federal agencies. Domestic U.S. entities and their domestic components are eligible; foreign organizations are not. The grant supports R33 applications with preliminary data demonstrating host biological patterns affecting probiotic responses, requiring further mechanistic validation through rigorous studies in animal models or humans.
Research must characterize person-specific features influencing probiotic efficacy and identify responder subgroups. The focus is on understanding how factors like microbiome, immune function, genetics, diet, age, and lifestyle affect probiotic outcomes. Studies should be well-designed mechanistic investigations building on established preliminary findings.
How to apply
Application links
Required documents
- NIH Application Form (SF-424 R&R)
- Project Narrative (Research Strategy)
- Preliminary Data/Supporting Materials
- Budget Justification
- Biographical Sketches (Key Personnel)
- Institutional Support Letters
Program contact
- 👤 National Institutes of Health
- 📧 grantsinfo@nih.gov
- 📞 301-402-2541
Funding track record
Recent awards under CFDA 93.866 from the last 3 years — real organizations that won funding through this same program.
Top 10 Largest Recent Awards
-
$463,372,200
-
$172,327,224
-
$115,145,694
-
$99,649,073
-
$93,275,174
-
$78,657,309
-
$75,825,492
-
$75,398,895
-
$70,985,470
-
$64,812,576
Top States by Funding
- MI 2 awards $511.9M
- CA 8 awards $511.1M
- MO 8 awards $437.0M
- IN 4 awards $303.9M
- PA 6 awards $298.0M
Source: USAspending.gov — federal spending transparency. Data covers last 3 years.
Funding history
Annual funding for this program — Federal obligations (CFDA 93.866). How funding has trended year over year.
| 2024 | $3,746,886,731 | |
| 2025 | $3,777,464,644 | |
| 2026 est. | $261,814,471 |
FAQ
Who can apply for this grant?
Universities, HBCUs, Hispanic-serving institutions, tribal colleges, nonprofits, faith-based organizations, and federal agencies are eligible. Foreign organizations cannot apply, but foreign components of U.S. organizations are allowed.
What type of research does this grant support?
R33 mechanistic studies that test whether host biological patterns (like microbiome, genetics, diet) predict or cause probiotic responses. You need preliminary data showing these patterns already.
What is the deadline?
The fixed deadline is June 2, 2027. Check NIH's grants.gov for any updates or rolling receipt dates.
Do I need preliminary data to apply?
Yes. Your application should demonstrate that host biological patterns affecting probiotic responses have been identified with supportive preliminary findings. You'll explain how you'll test these mechanistically.
Is cost-sharing required?
No. This is a non-matching grant, so you do not need to provide cost-sharing or institutional support.
💡 Tips for applicants
- Build your application around rigorously designed mechanistic studies, not discovery of new host factors. Reviewers expect strong preliminary data demonstrating your hypothesis.
- Focus on precision medicine angles: explain which subgroups of people respond to probiotics and why. Heterogeneity in response is the core scientific problem.
- Choose either animal models or human subjects, but justify your choice clearly. Explain why your model system will reveal mechanistic insights about human probiotic responses.
- Address the barriers to precision probiotic therapy head-on. Identify specific host features you'll study and explain how understanding them improves clinical outcomes.
- Align with NIH review criteria: innovation, feasibility, significance, and investigator qualifications matter deeply. R33s are transition-to-research awards, so show both preliminary promise and a clear path to clinical impact.
⚠️ Common mistakes
Submitting discovery studies instead of mechanistic validation. Reviewers expect preliminary data showing host factors already identified, not exploratory research. Weak or missing preliminary findings will cause rejection.
Focusing narrowly on safety or efficacy without explaining the person-specific biology driving probiotic response differences. This grant requires understanding the mechanism behind heterogeneity.
Proposing animal-only or human-only studies without justifying why that model answers your mechanistic question. Cross-justification strengthens competitiveness.
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