The NIH’s new funding opportunity, "Enhancing Mechanistic Research on Precision Probiotic Therapies" (PAR-25-210), is issued under the National Center for Complementary and Integrative Health (NCCIH) along with other NIH institutes, aiming to support research that addresses variability in human responses to probiotic therapies. This Notice of Funding Opportunity (NOFO) seeks proposals for studies that investigate how host biological patterns, such as genetics, microbiome composition, diet, and health history, influence probiotic responsiveness. The objective is to advance precision in probiotic interventions by identifying factors that lead to inconsistent treatment outcomes among different population subgroups. Applicants must submit an R33 application to undertake mechanistic studies that elucidate the causality of specific biological features in modifying responses to probiotics, targeting improvements in therapeutic efficacy.

The NOFO encourages research that explores how specific host characteristics modulate the effects of probiotics in ways that could lead to tailored interventions. Applicants may employ innovative animal models or human subjects for rigorously designed studies focusing on the mechanisms by which these host features influence outcomes. Proposals should be based on preliminary data demonstrating relevant biological patterns associated with probiotic effectiveness, and these studies must go beyond efficacy trials. Applications focusing on the initial identification of host patterns relevant to probiotics should apply to the companion R61/R33 opportunity, PAR-25-211.

Key dates for this funding opportunity begin with the earliest submission date on May 2, 2025. Applications are due by June 2, 2025, with additional deadlines extending through June 2027. All applications must include a Plan for Enhancing Diverse Perspectives (PEDP), ensuring that the proposed research strategy incorporates varied scientific viewpoints, geographical locations, and populations. The PEDP will be evaluated as part of the scientific merit assessment, as the NIH underscores the benefits of inclusivity in enhancing research quality and relevance.

Eligible applicants include higher education institutions, nonprofits, and for-profit organizations, with restrictions against non-U.S. entities. Projects may request budgets up to $350,000 per year in direct costs, not exceeding a total project period of four years. Applications may be new or resubmissions but must be scientifically distinct from any prior submissions. Required registrations for applicants include the System for Award Management (SAM), Grants.gov, and eRA Commons.

Review criteria prioritize the significance and innovation of the proposed study, particularly in how it advances knowledge on the interaction between probiotics and host biology. Studies must demonstrate scientific rigor and feasible methodology, with particular attention to reproducibility, sample diversity, and adequacy of plans to analyze diverse populations. The investigative team’s expertise, available institutional resources, and the clarity of the study’s design are also critical.

Prospective applicants are advised to consult NIH scientific contacts for guidance in aligning research proposals with NOFO priorities. This early engagement can help clarify project fit and potentially strengthen applications. Funded projects will be subject to NIH policies on data management, human subjects, and trial registration if applicable, and recipients must annually report on PEDP implementation.