Development of humanized microbiota mouse models of ME/CFS 2202

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.