# Interactions between the microbiome, metabolome, and immune system as underlying mechanisms of ALS pathogenesis

> **NIH ALLCDC R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2022 · $300,000

## Abstract

ABSTRACT
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive motor
neuron loss. Few treatment options with limited efficacy are available; therefore, new therapies are critically
needed. However, the underlying mechanisms of disease pathogenesis must be better understood to identify
disease biomarkers and therapeutic targets. Numerous biological systems and pathways are implicated in ALS
including the gut microbiome, the metabolome, and the immune system. Our own studies show that these
peripheral systems not only change over time but are associated with disease progression. In particular, the
gut microbiome is linked to clinical, metabolomic, and immune metrics, suggesting that there is an integrated
disease pathway network contributing to ALS. In the proposed research, we will examine the underlying
mechanisms by which these peripheral pathways impact ALS progression to enhance the design of future trials
and therapies. More specifically, we will examine the potential mechanisms by which changes in the gut
microbiome alter peripheral metabolites and immune cells in ALS. The overall objective of this Option B study
is to use the existing infrastructure and data pipelines from two ongoing R01-funded ALS studies to identify
cross-sectional and longitudinal associations between the ALS microbiome and clinical, metabolomic, and
immune metrics of disease. We hypothesize that the microbial composition of ALS subjects – either individual
bacterial communities or clusters of bacterial populations – will be associated with ALS progression as
measured by the ALS functional rating scale-revised (ALSFRS-R) (Aim 1). In addition, we hypothesize that
specific bacterial populations or population clusters will be associated with changes in both metabolic profiles
(Aim 2) as well as immune metrics (Aim 3) and that metabolic and immune changes will be associated with
altered disease progression. Completion of the study will identify integrated microbial, metabolic, and immune
pathways that can be used as biomarkers or therapeutic targets for future clinical trials.

## Key facts

- **NIH application ID:** 10609698
- **Project number:** 1R01TS000339-01
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Benjamin Joseph Murdock
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** ALLCDC
- **Fiscal year:** 2022
- **Award amount:** $300,000
- **Award type:** 1
- **Project period:** 2022-09-30 → 2025-09-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10609698

## Citation

> US National Institutes of Health, RePORTER application 10609698, Interactions between the microbiome, metabolome, and immune system as underlying mechanisms of ALS pathogenesis (1R01TS000339-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10609698. Licensed CC0.

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