# Gut microbiota-based biomarkers of Alzheimer's disease and its modulation by a ketogenic diet

> **NIH NIH R56** · WAKE FOREST UNIVERSITY HEALTH SCIENCES · 2020 · $604,248

## Abstract

Project Summary
Cognitive decline and Alzheimer's disease (AD) are major causes of morbidity and mortality worldwide and are
substantially burdensome to those affected, their caregivers, and society in general. There remain important and
formidable challenges in diagnosis, prognosis and prevention of this disease. Mild cognition impairment (MCI) is
characteristic of early stage AD, and interventions targeting MCI can prevent progression of AD. Currently, no
effective treatments are available and highly reliable consensus-based prognostic criteria for mild cognitive
impairment (MCI) are lacking. Moreover, there is insufficient evidence to support the use of pharmaceutical
agents or dietary supplements to prevent/treat MCI/AD. However, emerging research demonstrates that gut
microbiota influences gut-brain communication and pathology of AD. Others and our preliminary data show that
AD and MCI patient's gut harbors a perturbed and unique microbiota (dysbiosis) compared to cognitively normal
individuals, suggesting that the gut microbiota could be a source of new biomarkers for MCI/AD. Diet is the single
most significant modulator of the gut microbiota. A ketogenic diet (KD) is a powerful modulator of brain function
and improves AD pathology, along with modulating the gut microbiota. However, currently it is unknown whether
a modified Mediterranean KD (MMKD) primarily acts on the brain or the gut microbiota to ameliorate AD. Our
preliminary data show that in participants with MCI, MMKD improved the gut microbiota signature and markers
of AD in cerebrospinal fluid (CSF). In addition, gut microbiota signatures were significantly different in individuals
with and without MCI, with certain bacteria associated with MCI status. Overall, MMKD was effective to improve
AD markers in CSF and microbiota. However, certain people responded better (responders) than others (non-
responders) in improving markers of AD and changing unique microbiota signature. We thus hypothesize that
(a) gut microbiota-based biomarkers can predict MCI and MMKD response, and (b) MMKD acts through the
microbiota to reduce AD pathology. To test our hypotheses, we propose to use a cohort of participants with and
without MCI already being recruited for ongoing studies at Wake Forest Alzheimer's Disease Research Center
(ADRC) led by Dr. Craft. We will examine whether our new microbiota-based markers could strengthen MCI
prognosis and predict MMKD response, and test whether a MMKD modulates gut microbiota and thereby
improves AD pathology. Three specific aims are designed to: 1) establish if the gut microbiota signature can
predict MCI in humans, 2) determine whether gut microbiota signature can predict MMKD responders and non-
responders to ameliorate AD markers, and 3) assess whether gut microbiota mediates MMKD's beneficial effects
to ameliorate AD pathology. Completion of these state-of-the-art studies by a highly interdisciplinary team will
establish proof-of-concept that gut microbio...

## Key facts

- **NIH application ID:** 10247241
- **Project number:** 1R56AG064075-01A1
- **Recipient organization:** WAKE FOREST UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Hariom Yadav
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $604,248
- **Award type:** 1
- **Project period:** 2020-09-15 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10247241

## Citation

> US National Institutes of Health, RePORTER application 10247241, Gut microbiota-based biomarkers of Alzheimer's disease and its modulation by a ketogenic diet (1R56AG064075-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10247241. Licensed CC0.

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