The windows of the Krementsov Lab, located on the top floor of the Rowell Building, offer an expansive view of the UVM campus and Burlington’s skyline. But inside, Theresa Montgomery is focused on the microscopic world of trillions of bacteria, viruses, fungi, and other microbes known collectively as the gut microbiome. This internal ecosystem plays a crucial role in digestion, immunity, and overall health; and since joining the lab as a postdoctoral researcher in summer 2022, Montgomery has been studying how it influences the progression of the autoimmune disease multiple sclerosis (MS).
In MS, the immune system mistakenly attacks the protective covering of nerve fibers called the myelin sheath, disrupting communication between the brain and the rest of the body. The disorder primarily affects the brain, spinal cord, and optic nerve, and can cause muscle weakness, balance problems, fatigue, visual changes, cognitive impairment (such as difficulty thinking and remembering), and sleep disturbances. Older individuals with MS are also more prone to complications such as urinary tract infections, pneumonia, and infections of the blood and skin. The disease affects millions worldwide.
Montgomery has published two first-author, peer-reviewed research papers on her work. In her first paper, “Lactobacillaceae differentially impact butyrate-producing gut microbiota to drive CNS autoimmunity,” she used animal models of MS to experimentally modulate specific gut microbes and diet. Her findings demonstrated how certain microbes metabolize fiber as a protective mechanism in MS, and how these beneficial microbes can be antagonized by competing species. In her second paper, “Identification of commensal gut microbiota signatures as predictors of clinical severity and disease progression in multiple sclerosis,” co-authored with faculty at the Oklahoma Medical Research Foundation, she analyzed microbiome samples from a longitudinal study of people with MS. She then developed a statistical model capable of predicting future disease progression based on a person’s gut microbiome composition.
In addition to these publications, Montgomery successfully applied for independent postdoctoral fellowships from both the NIH (F32) and the National MS Society. She ultimately accepted the National MS Society fellowship, which will support her work for the next three years. Her research also generated key data for a three-year research grant awarded to the Krementsov Lab by the National MS Society in April 2025.
In the following Q&A, Montgomery shares insights into her research.
Q: Can you share the key findings of your first and second papers?
Montgomery: When it comes to the microbiome, we always talk about context-dependent effects: Who is there? What are they doing? And how does that interact with the host and other environmental factors? The major takeaway from the first paper is that the presence of a single species, in this case, L. reuteri, is sufficient to remodel the landscape of the gut microbiome and influence a disease like multiple sclerosis. We showed that colonization with L. reuteri leads to a depletion of other bacterial species that produce short-chain fatty acids. Because these fatty acids are reduced, MS-like disease is exacerbated in our mouse models.
The second paper is the foundation for my fellowship work on Akkermansia. I’m especially excited to continue that research. A major focus for me as a postdoc has been to build meaningful relationships with clinicians who work directly with MS patients, to make my research more translatable and impactful. Clinicians often tell me their patients want to know what they can do to take control of the disease, and sometimes clinicians aren’t sure what to recommend. Beyond frontline therapeutics, something like a vitamin K supplement or a probiotic such as Akkermansia could be a relatively easy and noninvasive option. In our ongoing work, we’re testing the role of vitamin K in preclinical models of MS to see whether it can help ameliorate the disease.
Q: How might your model change the way clinicians approach MS treatment?
Montgomery: The promise of the gut microbiome was that it would open up a whole new, tractable area of research to benefit health. In reality, we’re still in the early stages of developing predictive models. The first step is to replicate findings to ensure they’re applicable to the broader population, which is no small task. That’s something I’m working on now. Ideally, this research could help clinicians identify whether a species like Akkermansia is diminished in a patient’s microbiome, and whether that predicts future disease progression. That could lead to a test: What does your gut microbiome look like right now? Is Akkermansia low or high? If it’s low, maybe that patient needs a different therapeutic option, a supplement, or a revised treatment plan.
Q: When you talk about repeating this in other cohorts of people with MS, how long might that take?
Montgomery: One benefit of today’s multiomics approach is that cohort studies with deposited data are widely available. The largest study to date is the International MS Society study. Their data is publicly accessible, and I’ve been analyzing it. I’ve found that people with worsening disease also have diminished levels of Akkermansia. So that’s one species where I can show the finding holds up. As for how many studies are “enough,” that’s a separate question, but leveraging existing datasets definitely speeds up the timeline.
Q: Are there challenges in translating findings from animal models to humans?
Montgomery: We primarily use mice because we can control every environmental variable: the genetics of the mouse, and most importantly, the exact composition of the gut microbiome. In people with MS, geography and diet are major factors. Where you live affects your microbiome, so studying it in humans can be much noisier. Plus, we’re usually sampling at just one time point. That’s only a snapshot. In mice, we can study multiple time points across the entire disease course.
Q: Can you talk about how interdisciplinary collaboration is part of your work?
Montgomery: Good science today is inherently collaborative and ideally interdisciplinary. A major goal of my postdoc has been to expand my exposure to clinical translation. I collaborate with Dr. Yang Mao-Draayer, a practicing neurologist who sees MS patients and runs clinical trials. That partnership has strengthened my research. We also work with experts in all the omics areas we study, including those who developed the tools for analyzing the gut microbiome. These collaborations enrich the science and make it more directly impactful.
Q: What did being awarded your NIH and MS Society fellowships teach you about grant writing, scientific communication, and the academic research process?
Montgomery: Learning to communicate your science effectively is crucial, especially to diverse audiences. The National Multiple Sclerosis Society study has a unique review process for fellowships. For example: one panel includes scientists and clinicians, and another includes people living with MS. I love that. Your science needs to be accessible to laypeople. That’s a big rule for scientists: we need our research to be understandable and useful to everyone.
It’s also incredibly motivating. If a panel of people with the disease you study says, “This matters to me; I think it could improve my life,” that’s powerful motivation for the research you’re about to do.
Q: Your work also contributed to a major grant for the Krementsov Lab. How does it feel to see that kind of ripple effect?
Montgomery: Making the leap to fundable research tells me that what I’m doing matters; not just to other scientists, but also to clinicians and people living with the disease. That’s incredibly rewarding.
Q: What are the next steps in your research?
Montgomery: One project involves testing different forms of vitamin K and species of Akkermansi, which produce varying levels of vitamin K, to see which best suppresses disease in our preclinical models. We’re looking at whether it affects the entire disease course, disease progression specifically, or has different effects in males versus females. We’re also studying various metabolites produced by L. reuteri to determine whether they have pro- or anti-inflammatory effects in mice and how they modulate disease.
Q: How do you envision your work contributing to personalized medicine?
Montgomery: I love the idea of multiomic integration: taking different types of data, understanding how they relate, and using that to build predictive models and identify biomarkers. That could include gut microbes like Akkermansia, circulating metabolites, or inflammatory responses. These models could help clinicians assess whether someone is at risk for disease progression. That’s important because treatment options vary, and some have more severe side effects. Getting that right is key to offering a more personalized therapeutic approach. Beyond frontline therapeutics, we might also identify supplements or probiotics that could help.
Q: Is it possible to talk about curing MS?
Montgomery: The “Holy Grail” of MS is remyelination, the repair of the brain’s myelin sheath. MS is a demyelinating disease, and we don’t yet have a good option for repair once myelin is stripped away. One exciting aspect of vitamin K is that there’s some evidence it might play a role in remyelination. We’re going to test that directly in our preclinical models. If we can show repair in the brain, that would be a cure, or at least a complete halt and reversal of the disease’s effects. I’m excited to see if that’s possible. And since Akkermansia produces vitamin K, could it have the same effect?
Q: What advice would you give to early career researchers pursuing translational research?
Montgomery: Work hard and surround yourself with great people. My story is one of strong mentorship, lots of support, and passion for the work. There’s a reason I’m still at UVM. I think we do great research here. Being at a smaller institution fosters mentorship and internal collaboration, and that’s been a huge benefit to my work.
Montgomery earned her B.S. in Microbiology and Ph.D. in Cellular and Molecular Biology from the University of Vermont.