Restoring Key Functions to the Industrialized Gut Microbiome
NCCIH - National Center for Complementary and Integrative Health
About This Grant
SUMMARY The gut microbiome plays a key role in modulating host metabolism and immune responses. Industrialized populations, like U.S. residents, have gut communities with reduced microbial richness and missing key functions, particularly the degradation of microbiota-accessible carbohydrates (MACs, a component of dietary fiber) and the subsequent production of fermentation products, the short-chain fatty acids (SCFAs) acetate, propionate, and butyrate. These changes are linked to increased prevalence of a broad range of inflammatory diseases such as diabetes, metabolic syndrome, and autoimmune disorders. Our human dietary intervention study (NCT03275662) shows that reintroducing high dietary MAC levels in humans fails to restore SCFA production in most healthy adults, likely due to the scarcity of MAC-fermenting microbes in industrialized guts. A minority of participants with the highest microbiota richness did show decreased inflammatory markers and increased fecal butyrate during the intervention, termed “high-fiber responders”. We hypothesize that replenishing MAC-fermenting microbes in individuals with depleted microbiomes can increase SCFA production, reduce inflammatory markers, and improve host health. This project aims to target specific diseases with highly deteriorated gut microbiomes by repopulating the gut with bacteria that can ferment dietary MACs and deliver key metabolites to support human health and recovery. Aim 1 will characterize an existing repository of strains for MAC-degradation and perform additional isolations using a novel protocol for whole-food intact, low solubility fibers. SCFA profiles will be determined, along with functional assays to assess production of secondary bile acids and aryllactates. Aim 1 will result in a comprehensive repository of strains that can ferment various MACs into SCFAs and produce other key metabolites. Aim 2 will use an in vitro fermentation model to test microbial cocktails of 5-20 strains with a goal of optimizing production of SCFA and other metabolites. Augmentation of cocktails with strains possessing additional metabolic capabilities, such as hydrogen consumption or MAC- independent SCFA production pathways, will be explored to enhance SCFA output. Aim 2 will result in optimized candidate cocktails for further testing in mouse models. Aim 3 will evaluate the functionality of these cocktails in mouse models humanized with low richness gut microbiomes including those of people with metabolic syndrome. Mice will be fed a custom MAC-rich diets to promote cocktail engraftment. Impact on the microbiome will be assessed via metagenomic sequencing and SCFA and other metabolites measured. Host immune and metabolic responses will be profiled to understand the impact of enhanced SCFA production on inflammatory and metabolic status. This project leverages the expertise of PIs Sonnenburg and Martens including in the mechanisms connecting diet-microbiome interactions with host biology. Successful completion will provide foundational knowledge linking specific dietary MACs to microbiome function and yield trial-ready microbial cocktails aimed at restoring health-promoting functions in depleted microbiomes such as individuals with metabolic diseases.
Grant Summary
Restoring Key Functions to the Industrialized Gut Microbiome is a NCCIH - National Center for Complementary and Integrative Health grant providing up to $787K for university, nonprofit, healthcare org. Applications are due 2030-12-31 (open). Check eligibility and apply with FindGrants.
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Focus Areas
Eligibility
How to Apply
Up to $787K
2030-12-31
- 1Confirm your organization is eligible for Restoring Key Functions to the Industrialized Gut Microbiome from NCCIH - National Center for Complementary and Integrative Health, checking organization type, location, and any population or project requirements.
- 2Gather the required documents and information, including your organization details, project plan, and budget figures.
- 3Draft your application narrative and budget addressing the funder's priorities and review criteria. FindGrants can draft each section for you to review and edit.
- 4Review every section against the requirements checklist, then export a submission-ready application pack and submit it to NCCIH - National Center for Complementary and Integrative Health before the deadline.
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Restoring Key Functions to the Industrialized Gut Microbiome: Frequently Asked Questions
Who is eligible for the Restoring Key Functions to the Industrialized Gut Microbiome?
Restoring Key Functions to the Industrialized Gut Microbiome is offered by NCCIH - National Center for Complementary and Integrative Health and is generally open to university, nonprofit, healthcare org. It is open to organizations nationwide unless the funder specifies otherwise. Review the specific eligibility terms before applying, since funders set their own requirements around organization type, location, and the population or project being served.
How much funding does the Restoring Key Functions to the Industrialized Gut Microbiome provide?
Restoring Key Functions to the Industrialized Gut Microbiome provides up to $787K per award from NCCIH - National Center for Complementary and Integrative Health. Actual award sizes depend on the scope of your project, available program funds, and the number of applicants, so build a budget that reflects realistic, allowable costs rather than the maximum figure.
When is the Restoring Key Functions to the Industrialized Gut Microbiome deadline?
Applications for Restoring Key Functions to the Industrialized Gut Microbiome are due 2030-12-31 (open). Because deadlines can change, verify the date with the funder, NCCIH - National Center for Complementary and Integrative Health, and give yourself enough time to prepare a complete, competitive application before the close date.
How do you apply for the Restoring Key Functions to the Industrialized Gut Microbiome?
To apply for Restoring Key Functions to the Industrialized Gut Microbiome, confirm your eligibility, gather the required documents, and prepare a narrative and budget that address the funder's priorities. FindGrants guides you step by step and can draft each section, then exports a submission-ready application pack for this grant from NCCIH - National Center for Complementary and Integrative Health.