NIH funding opportunity – Advancing Translational and Clinical Probiotic/Prebiotic and Human Microbiome Research (R01)

Note:  participating organizations are NCI, NIDA, NCCIH, and ODS

This FOA encourages translational and clinical studies using a variety of pro/prebiotic carriers (foods, dietary supplements, etc.) to generate measurable functional evidence for the safety and effectiveness use of pro/prebiotics in maintaining health and/or prevent and treat diseases. If food is used, information should be readily available regarding the food matrix or relevant dietary and microbial composition of it.

Selection of probiotic strains will follow the FAO/WHO recommendations that probiotic microorganisms should not harbor transmissible drug resistance genes encoding resistance to clinically used drugs. Screening and selection criteria for probiotics(s) prebiotics should be focused on probiotic strains with demonstrated quality for a number of parameters in animals and fit for human consumption. Phase I and II a/b studies will require further proof of concept and testing assessments for a number of parameters, including antibiotic resistance assays, screening for virulence factors, resistance to host defense mechanisms and induction of hemolysis.

To ensure valid and reproducible results, appropriate animal models or human subjects enrolled in these studies must be characterized in terms of metabolic, biochemical, microbial, and health or disease status. The FOA will also support studies to develop new or to refine known biomarkers of health and disease with respect to the pro/prebiotics interventions. The impact of pro/prebiotic interventions must be measured and objectively documented for health and/or disease. Where needed, it is mandatory that the applicant (s) proposing clinical studies should provide sufficient details of plans and appropriately documented evidence of pre-IND (Investigational New Drug) status or other relevant regulatory correspondence at the time of application. Prior to any funded award being implemented in humans, investigators would be responsible for obtaining the approval for an IND from the United States Food and Drug Administration (FDA).

Probiotics, as defined, should be able to survive the passage through the digestive system and proliferate in the gut. Importantly, rigorous genomic and molecular identification and taxonomic profiling using omics based technologies of the species and the strain is crucial. The ability to remain viable at the target site and to be effective should be demonstrated for the strain used (including colony formation units, strain identification and characterization, transient adhesion or interaction with the intestinal epithelium and colonization of the colon, if pertinent). This shows the importance of the food matrix, including the amount of food that must be ingested in order to obtain the health benefit and proof for stability and viability of the strain in the food, until the consumption time. Food and supplements may be transporters of their own microbiomes as ingested and this aspect has to receive appropriate attention, due to microbe-microbe interactions. Understanding the functional niche, evolutionary and ecologic interplay among gut microflora and host physiology including its genetics is critical for designing therapeutic/preventive manipulations of the gastrointestinal microbiota

Common NIH research areas of interest may include, but are not limited to and are not in any priority order, the following:

1. Identification of the underlying mechanisms of action of pro/prebiotic formulation(s) to prevent and/or treat human diseases including conditions caused by emerging pathogens, such as bacteria, fungi and viruses .
2. Studies of pro/prebiotics interventions on: microbial composition, co-metabolism, microbial-host interactions, and microbiome resilience, as it affects local and systemic metabolism, gene expression and signaling pathways.
3. Interactions of pro/prebiotic formulations with diet, dietary supplements and/or dietary components, which produce microbial metabolites with measurable effects in risk reduction and disease prevention.
4. Development of predictive models to understand variability in response to pro/prebiotic interventions, as influenced by variables such as: nutritional status, dietary patterns, health status, age, gender, race, or other factors.
5. Characterization of probiotic strain activities on glycans and identification of glycan-mediated signaling pathways in health and disease, including further clarification of the effect of probiotics on mucin degradation and its consequences.
6. Examination of the effects of drug abuse (narcotics/opiates) on the efficacy of pre/probiotics and intestinal microbiome/microflora in populations with co-occurring infections including HIV, HCV and others; study how manipulation of the microbiome would alter the human virome and pathogenesis of complications of drug use such as HIV, HCV-related disease, and interactions with pro/prebiotics.
7. Studies of probiotics pharmacokinetics/pharmacodynamics in healthy and immunocompromised subjects.
8. Development and validation of diagnostic tests and biomarkers to evaluate early response to pro/prebiotics interventions.
9. Analysis of pro/prebiotic effect on resident biofilm-growing pathogens.
10. Analysis of interaction between pro/prebiotics with medications including antibiotics and other chemotherapeutic agents as it relates to bioavailability, treatment outcome, efficacy and adverse events.
11. Metabolomic profiling in samples from individuals/populations undergoing pro/prebiotic intervention to identify individuals/populations susceptible to the intervention
12. Microbial comparison of oral cavity and gut of individuals undergoing pro/prebiotic intervention.

Deadline:  standard dates apply

URL:    http://grants.nih.gov/grants/guide/pa-files/PA-15-127.html

Filed Under: Funding Opportunities