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Advancing Microbiome Science Through Multidisciplinary Mechanistic Investigations of the Human Microbiome in Health and Disease
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Topic Description
Post Date: January 15, 2026
Expiration Date: January 15, 2027
Purpose
This topic encourages mechanistic investigations of the human microbiome and its influence on host physiology in both health and disease. The purpose is to further expand this exciting field in new directions and to explore the application of microbiome-based data to advance novel interventions, disease prevention, detection and prognosis.
Background
The human microbiome consists of a diverse array of microorganisms living in and on the human body, the proteins and metabolites they produce and their interactions with the surrounding host environment. The microbiome is acquired at birth and comprised primarily of bacteria, along with viruses, fungi, and archaea. Human associated microbes contribute essential functions that are important for health and disruptions to the microbiome is associated with numerous conditions and diseases. The composition and functional output of these microbes, particularly in the gut, undergo changes throughout life and is influenced by factors like age, diet, environment and host genetics. Much of the existing knowledge comes from association studies at the population level; however, distinguishing between correlation and causation has been a persistent challenge due to the complexity of host-microbe interactions. Thus, new mechanistic research and investigations of the molecular interactions and pathways involved are needed to advance the field.
The gastrointestinal microbiome has been linked to a variety of conditions such as obesity, diabetes, and neuropsychiatric disorders but also acute and chronic diseases including infectious disease, immune-mediated diseases, and cancer. This connection has spurred the development of microbiome targeted therapies, which offer a new approach that can modulate, restore or protect microbiome function through the introduction of specific microbes or their metabolites. For example, chronic infectious diseases such as recurrent C. difficile infection, recurrent urinary tract infections, and bacterial vaginosis are often treated with multiple rounds of antibiotics. However, new microbiome-based therapies have the potential to restore microbiome function while reducing long-term antibiotic use. Similarly, new research has indicated a connection between the gut microbiome and the efficacy of immune checkpoint inhibitor therapy used for certain types of cancer, with specific bacterial species linked to patient responses.
A more mechanistic understanding of the human microbiome has the potential to transform our understanding of human health and disease with the possibility to advance personalized medicine. This topic seeks to encourage multidisciplinary, mechanistic research focused on microbiome function with the goal of translating this knowledge into disease treatment and prevention and to also understand how the microbiome can affect treatment responses. It also provides a broad opportunity to encourage exploratory research through investigator-initiated research.
Participating ICOs
NIAID encourages mechanistic microbiome studies on chronic infectious diseases such as recurrent C. difficile infection, recurrent urinary tract infection, and bacterial vaginosis. Additional areas include immune-mediated diseases such as rheumatoid arthritis, inflammatory bowel disease, type 1 diabetes, lupus, and allergies.
Projects should focus on evaluating how to alter the microbiome to treat and prevent disease, understand how the microbiome affects treatment response, and how a treatment of a disease may need to be altered to account for microbiome effects. Potential benefits of this research include a reduction in antibiotic use and resistance, reduced pathogen colonization, enhanced mucosal barrier function, mitigation of pathological inflammatory responses, prevention of food allergies, and enhanced immune system function. The goal is to provide opportunities for investigator-initiated exploratory research and enable participation of small businesses in product development.
ICO Scientific Contact:Ryan Ranallo, Ph.D.
[email protected]
Ingrid Fan, M.S.,
[email protected]
NCCIH seeks mechanistic microbiome research to advance understanding of the fundamental science of complementary interventions, such as natural products and mind & body (e.g., polyphenols, triterpenes, microbial-based therapies including probiotics, prebiotics. Conditions of interest include, but are not limited to, whole person health (e.g., health promotion and restoration, resilience, emotional wellbeing), stress, anxiety, metabolic disorders, and gastrointestinal dysfunction. Areas of scientific interest include, but are not limited to:
- Identifying novel microbiome targets or innovative mechanisms of complementary interventions, including functional interactions between microbiome and natural products
- Identifying and evaluating biomarkers that predict therapeutic response to complementary interventions
- Developing innovative microbiome methodologies/technologies to enhance or monitor the mechanistic effect of complementary interventions
Hye-Sook Kim
[email protected]
The NEI encourages mechanistic microbiome studies on chronic eye diseases such as age-related macular degeneration, diabetic retinopathy, and glaucoma. Projects understanding how dysbiosis in the gut microbiome and the factors they elaborate induce pathological changes in the host immune system and signaling pathways of the eye are encouraged. Researchers are also encouraged to use systems biology approaches, including multi-omics methods and deep sequencing techniques, combined with clinical, genetic, and epigenetic data to study chronic eye diseases. Furthermore, projects focused on developing machine learning algorithms to integrate large datasets, create models for calculating personalized eye disease risk, and guide the development of biomarkers and therapeutic approaches are strongly encouraged.
ICO Scientific Contact:Lisa Neuhold, Ph.D.
[email protected]
Nataliya Gordiyenko
[email protected]
James Gao
[email protected]
NIA encourages innovative research to advance our understanding of microbially-derived metabolites (MDMs) by:
- Developing technological breakthroughs (e.g. in vitro, organ-in-a-chip systems) to evaluate MDMs effects on gut barrier, blood brain barrier, and organ specific (e.g. brain, liver, skin, heart, muscle, bone) associated with aging and aging-related diseases.
- Use of pre-clinical models to characterize the mechanistic bidirectional effect of MDMs on rates of aging and cellular senescence (e.g. on immune and glial cells); understanding how the host-microbiome interaction (including viruses and fungi) changes with age (e.g. interorgan communication and organ function).
- Expanding our understanding of nutrient-derived microbial metabolites acting as neurotransmitters and modulating cognitive function and age-related dementias (AD/ADRD).
- Assessing pre-clinical and clinical effectiveness of pre- and probiotic interventions in modulating host immune function across the lifespan.
Roberto Flores-Munguia, PhD, MS, MPH
[email protected]
NIDCR encourages oral microbiome studies focused on development and understanding of microbiome directed therapies for oral disease including caries, periodontitis and oral cancers. Projects should focus on modulations of the oral microbiome that offer advantages such as reduced reliance on antimicrobials and longer lasting impact through establishment of health-related organisms and positive effects on systemic disease outside of the oral cavity. NIDCR particularly encourages innovative research that engineers the oral microbiome towards health through use of:
- Targeted pathogen elimination therapies through bacteriophage, small molecules or microbiota derived mediators
- Commensal driven modulation strategies and targeted therapies affecting oral homeostasis
- Models for assessment of the mechanisms driving the community from dysbiosis to health
Tamara McNealy, Ph.D.
[email protected]
The NIH Office of Autoimmune Disease Research in the Office of Research on Women’s Health (OADR-ORWH) areas of interest include:
- Projects that investigate sex influences on the human microbiome
- Projects that advance the translation of research advancements and evidence in women’s health into practical benefits for patients and providers
- Accelerating scientific discovery in diagnosis, treatment, prevention and cures and enhancing health for people with autoimmune disease
This office does not award grants. Applications must be relevant to the objectives of at least one of the participating NIH Institutes and Centers listed in this topic.
ICO Scientific Contact:Elena Gorodetsky, M.D., Ph.D.
[email protected]
Victoria Shanmugam, MBBS, MRCP, FACR, CCD
[email protected]
Tapan Bera, Ph.D.
[email protected]
Christina George, M.S.
[email protected]
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