# The microbiota-gut-brain axis in Alzheimers disease

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2021 · $327,408

## Abstract

ABSTRACT
 Host-microbe interactions are paramount for maintaining normal physiology of the human host, including
the brain and behavior. Bacterial colonization of the gastrointestinal (GI) tract, formation of GI mucosal barrier
function, neurogenesis, and myelination of neurons all occur during a critical developmental window in early
life. Thus, exposure to trauma such as stress, infection or inflammation during neonatal life could detrimentally
impact the developing microbiota, gut and brain (MGB) axis. Disrupted MGB axis signaling, including
dysbiosis, mucosal barrier defects and/or changes in behavior, occur in multiple diseases, including
Alzheimer’s disease.
 Antibiotics (Abx) are administered to children more frequently than adults, due to increased susceptibility to
bacterial pathogens. Since the MGB axis is developing during this critical time, Abx administration may have
long-lasting effects. Beneficial bacterial metabolites, including short chain fatty acids (SCFAs) can ameliorate
numerous pathologies, including dysbiosis, mucosal barrier dysfunction, inflammation and behavioral defects.
We have demonstrated that modifying the gut microbiota, for example using Lactobacillus-containing
probiotics, can prevent stress-induced MGB axis deficits following infection with a bacterial pathogen. We
hypothesize that administration of specific SCFAs can prevent neonatal Abx-induced deficits in the adult MGB
axis. Therefore, our primary objective is to address the effects of neonatal dysbiosis on the development of the
MGB axis using a model of neonatal Abx administration. Our overall goal is to determine whether intestinal
dysbiosis disrupts the gut-brain axis, and whether administration of SCFAs beneficially modulates the
MGB axis. This goal will be accomplished by the following Specific Aims: (1) Neonatal dysbiosis disrupts
myelination leading to neurodegeneration and (2) SCFAs regulate the MBG axis via myelination
 Taken together, these proposed studies will demonstrate whether neonatal dysbiosis disrupts the
developing MGB axis, impacting the microbiota composition, altering myelination in the brain, and causing
behavioral deficits in late adulthood. Furthermore, we will determine whether administering select SCFAs
ameliorates these effects, in part restoration of impaired myelination in the brain. Finally, our results may
promote use of SCFAs to prevent development MGB axis deficits, particularly in older adults.

## Key facts

- **NIH application ID:** 10283496
- **Project number:** 3R01AT009365-05S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Melanie G Gareau
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $327,408
- **Award type:** 3
- **Project period:** 2016-12-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10283496

## Citation

> US National Institutes of Health, RePORTER application 10283496, The microbiota-gut-brain axis in Alzheimers disease (3R01AT009365-05S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10283496. Licensed CC0.

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