# Topological Mapping of Immune, Microbiota, Metabolomic and Clinical Phenotypes to Reveal ME/CFS Disease Mechanisms

> **NIH NIH U54** · JACKSON LABORATORY · 2020 · $2,118,412

## Abstract

PROJECT SUMMARY OVERALL
We propose a Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Collaborative Research Center at
The Jackson Laboratory (JAX ME/CFS CRC) to identify the fundamental mechanisms by which a tri-
component network of systems—the microbiome, metabolism and the immune system—interact to cause or
exacerbate disease. ME/CFS is a debilitating illness that lacks widely accepted therapies for its management as
well as meaningful understanding of its biological underpinnings. Mounting evidence indicates a significant role
for immunological abnormalities, which are thought to contribute to disease progression. The microbiome
recently emerged as a potential contributor to immune perturbations, as it is intimately linked with immune
activation and homeostasis as well as host metabolic changes, and its dysbiosis has been linked to chronic
inflammation. Metabolomic studies suggest altered metabolic states in ME/CFS patients compared to healthy
controls, which could have downstream—or reciprocal—effects on sugar, energy levels, immune cell activity,
and microbial dysbiosis. However, small sample sizes, lack of cohesive clinical data and biological sample
collection, and overall focus on one component of the network has limited the impact of these studies. The JAX
ME/CFS CRC seeks to transform the landscape of knowledge of ME/CFS using a multi-disciplinary
systems biology approach to integrate phenotypic and functional immune changes in ME/CFS patients
with microbiome and metabolic parameters. We hypothesize that the immune system's etiological role in
ME/CFS is predicated on two major factors: 1) that immune cells are programmed to respond aberrantly to
environmental stimuli, and 2) that ME/CFS patients harbor microbes that aberrantly stimulate immune cells,
either directly or through metabolic byproducts. To probe this hypothesis, we structured the JAX ME/CFS CRC
around two integrated research projects and a prospective cohort of ME/CFS patients and healthy controls in
which blood, fecal samples and a range of clinical parameters are acquired longitudinally. Our Center will bring
together ME/CFS clinicians, experts in immunology, microbiome, and computational biology, and community
stakeholders to achieve our scientific goals and maximize the impact of our research on those affected by the
disease. Our Aims are: 1) Develop a comprehensive and prospective database of immune, metabolomics and
microbiome profiles of ME/CFS patients (Clinical Research Project); 2) Establish a platform for mechanistic
discoveries on role of ME/CFS microbiota and immune response (Basic Research Project); 3) Rapidly implement
recruitment of the ME/CFS prospective clinical cohort (Clinical Core); and 4) Coordinate an integrative,
multidisciplinary group in ME/CFS research (Admin Core). In addition, we will capitalize on both on scientific
expertise and vast mouse genetic resource of the JAX to develop highly collaborative inter-CRC projects to
understand role of e...

## Key facts

- **NIH application ID:** 10011892
- **Project number:** 5U54NS105539-04
- **Recipient organization:** JACKSON LABORATORY
- **Principal Investigator:** Derya Unutmaz
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $2,118,412
- **Award type:** 5
- **Project period:** 2017-09-30 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10011892

## Citation

> US National Institutes of Health, RePORTER application 10011892, Topological Mapping of Immune, Microbiota, Metabolomic and Clinical Phenotypes to Reveal ME/CFS Disease Mechanisms (5U54NS105539-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10011892. Licensed CC0.

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