Laboratory and Diagnostic Tools to Advance Microbiome-Brain Research (R41)

The complex and dynamic human microbiota profoundly affect human health and diseases in a variety of ways. Microbiota affect physiological processes including digestion, growth, immune defense and nervous systems. Mounting evidence indicates that components of the human microbiome change over time and are affected by a patient disease state and medication. It was also shown that microbiome composition influences mood disorder, level of stress and vice versa. This modulation of systemic immune response and physiology has an impact on pain and cognition in neurodegenerative, neurodevelopmental and behavior diseases. 

Illicit drug use and HIV are associated with altered nutrition and metabolism, depressed immune function, and decreased diversity of the intestinal microbiota. However, the mechanisms of microbial translocation and role of the microbiome in Substance Use Disorders (SUD) as well as in the majority of Central Nervous System (CNS) disorders are still unclear. There is a growing number of research projects that aim to develop a deeper understanding of the microbiome function and its vital and dynamic role in human health and diseases.

Several challenges have been identified that may significantly influence future studies of microbiome and CNS conditions:

- State of Knowledge. We still do not have enough understanding and data about the microbiome contribution to brain diseases.

- Sample Quality. The samples for microbiome analysis have reduced stability. Additional research is needed to identify the optimal sample collection and preservation.

- Cost. The cost of microbiome analysis remains high.

- Time and Labor. The prolonged analysis and lack of available microbiome monitoring services are making it difficult to study the dynamic of microbiota after changing the diet, the life style or having medical treatment.

Addressing technological gaps in microbiome research would allow researchers to perform the integrative analysis of the human microbiome; to improve our knowledge regarding the pool of mobile genetic and metabolomic elements associated with the human gut microbiome and SUD; and to create databases or catalogs of bacterial metagenomics associated with SUD and other CNS conditions.

NIDA expects that small business will enable innovative technologies for microbiome research and diagnostics. Availability of developed tools/resources may facilitate research to clarify associations between the human microbiome and the brain. Through an STTR grant, this FOA will support cooperative R&D projects between small business concerns and research institutions to establish the technical merit and feasibility of ideas that have potential for commercialization.

The specific scope of National Institute on Drug Abuse (NIDA): This FOA aims to support the development of novel analytical tools, technologies and research resources to study the microbiome, including its composition, genetics, and bioactivity.  

Examples of these analytical tools, technologies and research resources may include, but are not limited to:

• Novel high-throughput sequencing (as it relates to microbiome samples)
• Flow cytometry and/or cell sorting technologies to investigate the composition, specificity and dynamics of the microbial communities
• Laboratory assays for preparation and processing of samples for microbiome analysis
• Diagnostic and laboratory tools to isolate, dissect, and analyze complex microbial communities in various tissues
• Clinical diagnostic tests for express microbiome analysis
• Gut microbiome monitoring systems or tests for the analysis of functional and genetic dynamics of microbiota
• Microbiome targeted small molecular and biological markers
• Informatics tools and resources for metagenomics data, databases of genome sequences, and informational resources about the association of microbiome strains with human health and diseases
• Metagenomic tools for drug screening

The specific scope of National Center for Complementary and Integrative Health (NCCIH):

NCCIH is interested in the role of gut microbiota, and the potential for pre- and probiotics in modulating gut microbiota to prevent and treat a variety of diseases, and disorders including those that may be associated with the brain-gut axis (e.g., pain and anxiety).  Novel assays (e.g., high dimensional methods, analytical and informatics tools) need to be developed and widely used to characterize and determine the bioactivity of, and interactions among prebiotics, probiotics and commensal microbiota. Tool-enabling discovery examining the range and complexity of bioactivity, and diversity among prebiotics and probiotics and gut-microbiota will advance research, and clinical application aimed at the diagnosis, treatment, and prevention of disease and disorders.

See Section VIII. Other Information for award authorities and regulations.