Engineering Precision Probiotics for Lactate Metabolism and Organ Recovery
NCCIH - National Center for Complementary and Integrative Health
About This Grant
PROJECT SUMMARY/ABSTRACT The goal of this application is to (R61) identify microbial genes, pathways, and strains in hospitalized patients that influence lactate metabolism and (R33) develop a mechanistic probiotic strategy that (1) protects probiotics from co-administered antibiotics and (2) augments host lactate metabolism through precision engineering, contributing to organ recovery and whole-person health. The major barrier to probiotic efficacy among hospitalized patients is concurrent antibiotic administration. Hospitalized patients routinely receive broad-spectrum antibiotics with potent activity against commensal bacteria and probiotics, rendering probiotic trials in hospitalized patients doomed to futility. Lactate metabolism represents an optimal target for therapeutic microbiome modulation. Lactate is the most commonly used metabolic biomarker in hospitalized patients, and participates in metabolic dysfunction. Recent studies in exercise have revealed that blood lactate enters the gut, where it is metabolized by commensal bacteria into metabolites that re-enter the systemic circulation, participate in organ homeostasis. Our team has recently made two fundamental discoveries: (1) Commonly-used antibiotics with activity against anaerobic gut commensals worsen patients’ clinical outcomes and decrease patients’ clearance of blood lactate. (2) By integrating lactate oxidase into an established probiotic strain, we have shown that an orally administered probiotic can accelerate lactate clearance in murine models of lactic acidosis. Aim 1 (R61, Phase 1): Identify gut microbial features associated with variability in host lactate metabolism and clinical outcomes. We will leverage a large, existing biobank of rectal swabs from 1,550 hospitalized patients and a natural experiment created by the 2015–16 piperacillin-tazobactam shortage. Aim 1a: Use instrumental variable analysis to quantify the impact of anaerobe-depleting antibiotics on gut microbial composition and lactate clearance. Aim 1b: Identify microbial gene pathways associated with lactate metabolism and clinical outcomes. Aim 2 (R33, Phase 2): Expand, refine, and translate precision probiotic strategies by testing the causal role of microbial features identified in Aim 1. Aim 2a: Test ribaxamase-mediated protection of B. subtilis in the presence of β-lactam antibiotics, evaluating viability, colonization, and metabolic activity in vivo. Aim 2b: Incorporate microbial genes or functions identified in Aim 1 into B. subtilis and test their effect on lactate metabolism in murine models of lactic acidosis. Aim 2c: Evaluate the most effective strategy in a validated swine model of infection-associated lactic acidosis to assess translational relevance.
Grant Summary
Engineering Precision Probiotics for Lactate Metabolism and Organ Recovery is a NCCIH - National Center for Complementary and Integrative Health grant providing up to $546K for university, nonprofit, healthcare org. Applications are due 2027-07-31 (open). Check eligibility and apply with FindGrants.
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Eligibility
How to Apply
Up to $546K
2027-07-31
- 1Confirm your organization is eligible for Engineering Precision Probiotics for Lactate Metabolism and Organ Recovery 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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Engineering Precision Probiotics for Lactate Metabolism and Organ Recovery: Frequently Asked Questions
Who is eligible for the Engineering Precision Probiotics for Lactate Metabolism and Organ Recovery?
Engineering Precision Probiotics for Lactate Metabolism and Organ Recovery 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 Engineering Precision Probiotics for Lactate Metabolism and Organ Recovery provide?
Engineering Precision Probiotics for Lactate Metabolism and Organ Recovery provides up to $546K 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 Engineering Precision Probiotics for Lactate Metabolism and Organ Recovery deadline?
Applications for Engineering Precision Probiotics for Lactate Metabolism and Organ Recovery are due 2027-07-31 (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 Engineering Precision Probiotics for Lactate Metabolism and Organ Recovery?
To apply for Engineering Precision Probiotics for Lactate Metabolism and Organ Recovery, 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.