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

> **NIH NIH U54** · JACKSON LABORATORY · 2021 · $835,979

## Abstract

PROJECT SUMMARY BASIC RESEARCH PROJECT
Our goal in this project is to investigate the molecular mechanisms by which the ME/CFS microbiome
interacts with the immune system to cause disease. Abnormalities in immune activation are likely key
contributors to ME/CFS disease severity. However, we do not know to what extent these abnormalities are: 1)
microbial in origin, i.e., caused by microbial dysbiosis in ME/CFS patients; 2) caused by metabolites produced
by microbiota that influence the immunological or metabolic pathophysiology; or 3) caused by genetic or
environmental perturbation of immune sensitivity in ME/CFS patients. There is thus a strong need to identify the
immune cells, bacteria, and molecular pathways that drive abnormal immune activation in ME/CFS. Here, we
will interrogate microbes and immune cells harvested from ME/CFS patients through complementary pipelines,
each designed to isolate one side of the microbe-immune axis. The microbial pipeline will compare ME/CFS-
related bacteria collected from patients to bacteria from healthy controls using a set of relevant immune assays.
The immune pipeline will compare immune cells collected from ME/CFS patients to healthy immune cells,
exposing both to a battery of microbial triggers and immune cell activators. Together, these pipelines will pinpoint
with molecular resolution the specific immune-mediated disease triggers unique to or significantly enriched in
the ME/CFS condition. We expect to determine the relative contributions of microbes and immune cells toward
the immune pathology observed in these patients. We also expect to identify how ME/CFS-related gut microbes
impact different compartments of the immune system and to identify the immunomodulatory metabolite repertoire
that underlies these interactions. This research project is highly synergistic with the clinical project, in that
together they will establish microbial and immune correlates of ME/CFS disease severity and a framework for
disease mechanisms. This project will also contribute to the goals of the CRC through: characterization of
microbial and immune cellular and molecular mechanisms, identification of potential new therapeutic targets with
characterized mechanism of action, and identification of potential microbial or transcriptional triggers,
biomarkers, and risk factors. Our Specific Aims are: 1) To identify immunomodulatory bacterial strains from
ME/CFS patients that may underlie immunopathology (Microbial Pipeline); and 2) To determine the response of
ME/CFS patient immune cells to microbial modulators based on transcriptomic interrogation and epigenetic
states (Immune Pipeline). Impact: By probing the immune responses of ME/CFS patients to microbial stimuli,
we will define the molecular mechanisms by which ME/CFS-related gut microbes mediate immune activation.
This work will also lay the foundation for rational discovery of therapeutics that target microbe-immune
interactions, and development of engineered probioti...

## Key facts

- **NIH application ID:** 10248308
- **Project number:** 5U54NS105539-05
- **Recipient organization:** JACKSON LABORATORY
- **Principal Investigator:** Julia Oh
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $835,979
- **Award type:** 5
- **Project period:** 2017-09-30 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10248308

## Citation

> US National Institutes of Health, RePORTER application 10248308, Topological Mapping of Immune, Microbiota, Metabolomic and Clinical Phenotypes to Reveal ME/CFS Disease Mechanisms - Basic Research Project (5U54NS105539-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10248308. Licensed CC0.

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