# Understanding the Microbiome-gut-brain axisn Alzheimer disease and its Role in Cognitive Decline

> **NIH NIH RF1** · UNIV OF MASSACHUSETTS MED SCH WORCESTER · 2020 · $3,281,382

## Abstract

ABSTRACT
The concept of the “microbiota-gut-brain axis”, which originated from behavioral studies in microbiome-
reconstituted mice, has advanced to current research that supports the microbiome may be responsible for some
of the most devastating neurodegenerative disorders, including Alzheimer's Disease (AD). Recent studies have
interrogated this connection among the intestinal microbiome and identified significant changes in the abundance
of certain taxa in AD patients. Thus, one current theory is that AD pathogenesis is closely related to the imbalance
of the gut microbiome and may originate in the gut. Our group has recently published findings among a cohort
of nursing home elders demonstrating a dysbiotic pattern in AD elders that is hallmarked by a reduction in the
prevalence of bacteria with anti-inflammatory properties, as well as an acquisition of taxa that are known to cause
pro-inflammatory states. In this proposal we will: 1) leverage our current nursing home experience to enroll elders
assessing cognitive decline; 2) advance our work within the local Senior Centers' elder groups to enroll a
comparative community-dwelling cohort; 3) determine both microbiota taxonomy and gene function among these
elders; 4) utilize stool samples to determine how the microbiome can induced intestinal inflammation and how
this correlates back to observed systemic inflammation; and 5) study the microbiome metabolic product
differences and explain how these products can influence microglia functioning. We hypothesize that there is a
characteristic dysbiotic microbiome among AD elders, regardless of living environment, and that the level of
inflammation-type dysbiosis positively correlates with both local and systemic inflammation and eventually
cognitive decline. We further hypothesize that the AD microbiome metabolites negatively impact microglial
functioning. Specifically, in Aim 1 we will assess characteristics of the AD elder's microbiome from different
environments in comparison to elders without dementia and longitudinally assess the microbiome composition
and correlate it to changes in cognition. In Aim 2 we will determine the extent of microbiome dysbiosis among
AD elders, correlate this with the level of induce (in vivo/vitro) epithelial dysfunction, and then back to elder
cytokine markers of inflammation and T cell population markers of immunosenescence. Finally, in Aim 3 we will
perform metabolomics to identify metabolite profile differences between AD elders and those without dementia
and use the identified metabolites in our in vivo/vitro assays to describe its effects on microglial functioning. This
work takes a critical step forward to bridge microbiome associations with AD to causality by showing how the AD
elder's microbiome dysbiosis observed can adversely affect intestinal epithelial homeostasis leading to systemic
inflammation, inflammation-causing immunosenescence, and ultimately cognitive dysfunction. It will also
describe the microb...

## Key facts

- **NIH application ID:** 9974848
- **Project number:** 1RF1AG067483-01
- **Recipient organization:** UNIV OF MASSACHUSETTS MED SCH WORCESTER
- **Principal Investigator:** John Patrick Haran
- **Activity code:** RF1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $3,281,382
- **Award type:** 1
- **Project period:** 2020-09-15 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9974848

## Citation

> US National Institutes of Health, RePORTER application 9974848, Understanding the Microbiome-gut-brain axisn Alzheimer disease and its Role in Cognitive Decline (1RF1AG067483-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9974848. Licensed CC0.

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