Development of humanized microbiota mouse models of ME/CFS 2202, 2025, Gabrie

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Journal Article

Development of humanized microbiota mouse models of ME/CFS 2202​

Katherine Gabrie
The Journal of Immunology, Volume 214, Issue Supplement_1, November 2025, vkaf283.149, https://doi.org/10.1093/jimmun/vkaf283.149
Published:

20 November 2025


Abstract Description​


Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a multisystemic, debilitating, and neglected illness for which no accepted efficacious treatments are currently available.

Our preliminary data, as well as our previous published studies, show that ME/CFS cases have alterations in gastrointestinal mucosal immunity and mitochondrial homeostasis.

Several other studies have described significant alterations in the composition of the gut microbiome in ME/CFS cases, when compared to age and gender-matched controls, potentially implicating a pathological role for a dysbiotic microbiota in the progression of ME/CFS through the gut-microbiota-brain axis.

We hypothesize that by conducting a fecal microbiota transplantation (FMT) with stool from ME/CFS cases into mice that are engrafted with a functional human immune system, we can develop an animal model that will replicate ME/CFS-associated pathology.

We further hypothesize that this model can be used to conduct ME/CFS research that is not practical or possible when working with human subjects. ME/CFS research has been severely hindered due to a lack of an animal model, resulting in a critical knowledge gap in our understanding of this disease.

We intend to resolve this by developing the first single humanized microbiota-associated (HMA) and double humanized microbiota-associated (dHMA) mouse models of ME/CFS.

Funding Sources
Supported by NIH/NIAID project number 1R21AI183042-01.

Topic Categories
Mucosal and Regional Immunology (MUC)
Animals - Rodent Molecules - Antibodies Antigens/Peptides/Epitopes Processes - Neuroimmunology Techniques/Approaches - Molecular Biology
Issue Section:
Abstracts
Collection: American Association of Immunologists Journals
 
This seems to be the main idea but not seems highly doubtful if this will work
We hypothesize that by conducting a fecal microbiota transplantation (FMT) with stool from ME/CFS cases into mice that are engrafted with a functional human immune system, we can develop an animal model that will replicate ME/CFS-associated pathology
 
In Specific Aim 1, we will characterize and transplant stool from ME/CFS cases and healthy controls into common C57BL/6J laboratory mice, which have a normal murine immune system, as well as mice that are engrafted with a functional human immune system. We will then evaluate these mice for exercise intolerance, neurocognitive dysfunction, and sleep disturbances; behavioral alterations consistent with those observed in human cases.
In Aim 2, we will pathologically evaluate these mice to identify changes in the gut and the brain that potentially implicate the altered microbiota in ME/CFS pathophysiology.
These studies will lay the foundation for a larger research focus to identify ways to target the gut-microbiota brain axis in the prevention and treatment of ME/CFS.
 
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