Campus | Pexels by Pixabay
Campus | Pexels by Pixabay
A recent publication by a Montana State University research team examining a rare neurological disease was recognized for its impact by the journal Nature Communications last month. The team included graduate students and faculty from MSU’s College of Agriculture and College of Letters and Science.
Researchers and graduate students from MSU’s Department of Chemistry and Biochemistry and Department of Microbiology and Cell Biology examined the impacts of Familial dysautonomia, or FD, on the gut microbiomes and metabolisms of patients in collaboration with researchers at the New York University School of Medicine.
Graduate students Alexandra Cheney and Stephanann Costello and research scientist Nick Pinkham wrote the paper, titled “Gut Microbiome Dysbiosis Drives Metabolic Dysfunction in Familial Dysautonomia.” The paper was selected by the journal’s editors as a highlighted publication in January, a distinction that showcases the 50 best recently published papers. Researcher professor Frances Lefcort and professors Valérie Copié and Seth Walk served as principal investigators on a $2.9 million grant funding the project.
Familial dysautonomia, also known as Riley-Day Syndrome, is a rare neurological disorder that can be traced back to a genetic mutation documented in some members of the Jewish population in eastern Europe. The disease causes a variety of symptoms including slowing physical growth and development and impairing the function of organs such as the heart, lungs, kidneys, gastrointestinal tract and eyes. It has no known cure, and treatment generally takes the form of symptom management.
Only around 350 people in the world have familial dysautonomia, and the MSU team worked with samples from about 14% of them. The team specifically examined how the disease affects the gut microbiome, comparing individuals with FD to “paired” relatives – members of their family who did not have the same genetic mutation.
“The gut-brain axis has been a growing topic. It's getting a lot of interest right now, especially the gut microbiome, and that itself is a relatively new field of science,” said Cheney, a doctoral student in Copié’s lab and one of the paper’s lead authors.
Cheney, Costello and Pinkham examined how FD impacts the diversity and concentrations of metabolites – chemicals and other substances necessary for the body to break down nutrients from food. The researchers believe the neural degeneration caused by FD disturbs both the gut microbiome and the metabolism, said Costello, a doctoral student who is a member of MSU’s Sloan Indigenous Graduate Partnership Scholarship Program and who also works in Copié’s lab.
“That creates a feedback loop between the gut microbiome, the central metabolism and the brain and nerves to facilitate further neurodegeneration and disease progression,” she said.
Costello extracted metabolites from patient samples through a process called NMR, or nuclear magnetic resonance. The team then compared the metabolites in the FD patients with those in their relatives who didn’t have the disease.
They found that the metabolites present in the patients’ guts were less diverse than in their unaffected relatives. While there’s no one perfect example of a healthy microbiome, Cheney said, diversity is key, and finding ways to improve microbiome diversity could impact patient health.
Cheney’s work involved analyzing metabolites from blood samples. For her, the research was appealing for its interdisciplinary nature and the unique applicability of research into FD.
“The other diseases that FD can relate to, like Alzheimer's, Parkinson's and ALS, also often include gut issues, and they might be similar to what we're seeing in this disease,” said Cheney. “So, we can apply it to not only this disease, which is under-studied, but to other diseases that aren't really breaching the topic of the gut-brain axis yet.”
Pinkham referred to his part in the research as creating a story from the data Cheney’s and Costello’s analyses generated. A research professional in the Walk Lab, Pinkham received his master’s in microbiology from MSU in 2017. With modeling and data analysis, he identified patterns among the differences between FD patients and the unaffected relatives.
“We found something that was different between people with the disease and those without the disease, and from that we can identify intervention strategies,” Pinkham said. “So, the thing to do next would be to explore those intervention strategies with patients. It’s really cool to be part of something that goes full circle like that.”
Those potential interventions could be anything from nutritional supplements to the emerging practice of microbiome transplants, which involves transferring bacteria from a healthy individual into an affected patient. Cheney, Costello and Pinkham hope that future treatment for FD could shift from symptom management to addressing the cause of those symptoms.
“There are a lot more questions that came with this project, that I unfortunately won't be here to solve,” said Cheney, who will finish her doctoral work this year. “But someone can, and they should.”
Valérie Copié, Department of Chemistry and Biochemistry: vcopie@chemistry.montana.edu or 406-994-7244; Seth Walk, Department of Microbiology and Cell Biology: seth.walk@montana.edu or 406-994-2649; Frances Lefcort, Department of Microbiology and Cell Biology: lefcort@montana.edu or 406-995-5656
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