What if your mouth could reveal important clues about multiple sclerosis?
In this interview, Professor Dr. Ashutosh Mangalam, immunologist and microbiome researcher at the University of Iowa, explores the emerging role of the oral microbiome in MS. While the gut microbiome has received a lot of attention in recent years, research now suggests that the bacterial communities in our mouth may also influence inflammation, immune balance, and disease activity.
Together, we discuss
what the microbiome is and why it matters for people living with MS,
how the oral microbiome differs in people with relapsing-remitting MS,
why beneficial bacteria are lost while potentially harmful ones increase,
and how microbial metabolites could one day support MS monitoring or treatment through simple saliva tests.
Professor Mangalam explains complex science in an accessible way and shares a hopeful outlook on how oral health, lifestyle factors, and microbiome research may complement future MS care.
If you are curious about MS research beyond medications and MRI scans – and want to understand how everyday aspects like oral health might matter – this conversation is well worth reading.
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What led you to MS and microbiome research?
Prof. Dr. Ashutosh Mangalam: I’m a professor of pathology at the Carver College of Medicine at the University of Iowa. Before that, I worked at the Mayo Clinic in Rochester. I’m an immunologist by training, and my early work focused on genetic factors linked to multiple sclerosis.
MS runs in families, and I worked with HLA transgenic mouse models to study disease mechanisms. During that work, we made an unexpected observation: certain bacteria could induce anti-inflammatory immune responses. One of them was Prevotella histicola.
That finding sparked my interest in the microbiome. Around 2007–2008, we received funding to study how specific bacteria influence MS and arthritis in animal models. Later, when we moved into human microbiome studies, we found that Prevotella species were reduced in MS patients. Despite initial skepticism, these findings were eventually confirmed by multiple groups, and that’s how I became deeply involved in microbiome research.
What is the microbiome, and why is it relevant for MS?
Prof. Dr. Ashutosh Mangalam: I always like to start with a basic question: why do we have microbiota at all?
Microbiota refers to the microorganisms themselves—bacteria, viruses, fungi—while microbiome refers to their genetic content. From an evolutionary perspective, humans outsourced part of digestion to microbes. Diet is the biggest factor shaping our microbiota.
These microbes do far more than digest food. Germ-free mice, for example, do not develop a normal immune system. About 90% of serotonin is produced in the gut, which is why it’s often called the second brain. We are not just human cells—we are a holobiont, a complex ecosystem.
When this ecosystem is balanced, it supports immune homeostasis. When it is disturbed, inflammation and disease risk increase.
Beyond the gut, which microbial communities matter most in MS?
Prof. Dr. Ashutosh Mangalam: The gut is very important, but the oral microbiome is also highly relevant. We are currently studying nasal and skin microbiomes as well. All of them likely play a role.
Different body sites need different conditions. In the mouth, maintaining a neutral pH is critical. Many bacteria that are reduced in MS help lower acidity or buffer the environment. When they disappear, pathogenic bacteria can grow more easily.
What role do microbial metabolites play?
Prof. Dr. Ashutosh Mangalam: Metabolites are the real currency of the microbiome. Bacteria matter because of what they produce, not because of their names.
Different bacteria can perform the same function. What matters is whether key metabolic pathways are present. In our oral microbiome study, we found reduced levels of hypotaurine, a molecule involved in redox balance, myelination, and nerve health. That suggests functional changes that may be relevant for MS.
What did your oral microbiome study in relapsing-remitting MS show?
Prof. Dr. Ashutosh Mangalam: The main finding was dysbiosis—a clear shift in the bacterial community compared to healthy controls.
Beneficial bacteria such as Streptococcus, Actinomyces, Veillonella, Rothia, and Carnobacterium were reduced. These bacteria help maintain oral pH. In contrast, gram-negative bacteria like Fusobacterium increased.
We also saw that microbial communities in MS were fragmented. In healthy people, the metabolic network is dense and interconnected. In MS, that network largely disappears.
Why is the loss of hypotaurine important?
Prof. Dr. Ashutosh Mangalam: Hypotaurine is involved in redox regulation and supports myelin and nerve growth. Lower levels suggest a more oxidative, inflammatory environment in the mouth.
At this stage, we cannot say whether this is a cause or a consequence. That’s why longitudinal studies are so important.
Could saliva be used for monitoring or diagnosis?
Prof. Dr. Ashutosh Mangalam: That is one of our goals. Saliva is easy to collect and has high patient compliance. We are currently following MS patients longitudinally to see whether oral microbiome changes correlate with relapses or disease progression.
If successful, saliva could become a useful biomarker—not just for monitoring, but also for prognosis.
Can the oral microbiome become a therapeutic target?
Prof. Dr. Ashutosh Mangalam: Potentially, yes. The oral cavity is easier to manipulate than the gut. In the future, restoring beneficial oral bacteria might also influence the gut microbiome and systemic inflammation.
Can people influence their oral microbiome through habits like diet, hygiene, or avoiding smoking?
Prof. Dr. Ashutosh Mangalam: Smoking definitely has an effect on inflammation and immune responses. In our MS cohort, however, very few people were active smokers. Most had stopped smoking at least ten years earlier, which made it difficult for us to analyze smoking effects in detail within our own data. Other research groups, though, clearly show that smoking can worsen inflammation and disease outcomes.
Oral hygiene is much more clearly linked to the oral microbiome. I work closely with colleagues from the dental school, and one thing that becomes very obvious is the importance of periodontal health. Plaque buildup, gum inflammation, and untreated periodontal disease all change the oral environment and influence which bacteria can survive.
Diet also matters. Acidic drinks such as soda create an acidic oral environment, which promotes the growth of pathogenic bacteria. In contrast, a more balanced oral environment supports bacteria that help maintain neutral pH and microbial homeostasis. Good oral hygiene and regular dental care are therefore practical ways to influence the oral microbiome.
Why is oral health and regular dental care especially important for people with MS?
Prof. Dr. Ashutosh Mangalam: Oral health is often underestimated, even though it is tightly connected to overall health. Small inflammatory changes in the mouth can have effects far beyond the oral cavity.
MS is a multifactorial disease. Genetics, immune regulation, metabolism, and inflammation all interact. Poor oral hygiene, periodontal disease, chronic plaque buildup, stress, and acidic diets can all contribute to a pro-inflammatory environment in the mouth.
Because the body functions as one integrated system, inflammation in the oral cavity can influence gut health and systemic immune responses. We are currently testing this concept in animal models to move beyond correlation and show causation—specifically whether oral inflammation can worsen disease severity.
Taking oral health seriously is therefore not just about teeth, but about reducing overall inflammatory burden in people living with MS.
How often would oral microbiome testing need to be done to be useful for disease monitoring?
Prof. Dr. Ashutosh Mangalam: This is an important question, and the honest answer is that we don’t yet have a definitive guideline. MS is highly individual, and disease activity differs greatly from person to person.
My current view is that oral microbiome testing could be aligned with regular clinical visits. For people with relatively stable disease, annual testing might be sufficient. For those with more active disease or frequent relapses, testing every three to six months could be more informative.
At the moment, this is based on clinical reasoning rather than hard evidence. Our ongoing longitudinal studies—where we follow patients for several years—are designed to answer exactly this question in a data-driven way.
Could combining oral, gut, and blood-based markers lead to more personalized MS treatment in the future?
Prof. Dr. Ashutosh Mangalam: Yes, I strongly believe so. Personalized medicine works best when you have multiple complementary data points.
Blood markers reflect systemic inflammation and immune activation. Oral samples capture local changes and are easy to collect, making them practical for repeated measurements. The gut microbiome, because of its sheer size and metabolic capacity, likely acts as a central engine that shapes immune responses throughout the body.
When you combine oral, gut, and blood-based markers, you reduce the risk of missing important signals. Together, they could provide a much more complete picture of disease activity and treatment response, paving the way for truly personalized MS care.
What open questions are you most eager to explore next?
Prof. Dr. Ashutosh Mangalam: Our lab follows a bedside-to-bench-to-bedside approach. We start with patient data, identify patterns in cross-sectional and longitudinal studies, and then test hypotheses in animal and in vitro models.
One of my biggest goals is to move beyond simply naming bacteria. We now know that focusing on single bacterial species is often not enough, because different bacteria can perform the same function. What really matters are the metabolic pathways and metabolites involved.
We are working on identifying which of the thousands of microbial metabolites are truly relevant for immune regulation and MS disease activity. This is technically challenging, but we are making progress both bioinformatically and experimentally.
Ultimately, I want to understand which metabolic functions are missing in MS and how we can restore them in a targeted way.
What do you hope to see in MS research over the next years?
Prof. Dr. Ashutosh Mangalam: I would like to see more collaboration between research centers, more data sharing, and better integration of microbiome, metabolomics, and clinical data.
Metabolomics in particular needs more investment. Sequencing has become relatively inexpensive and accessible, but metabolite analysis is still limited to specialized centers. I believe many answers lie there, and I hope we will see better tools, lower costs, and more standardized pipelines in the coming years.
How close are we to turning microbiome research into real-world tools – such as saliva tests or microbe-based therapies?
Prof. Dr. Ashutosh Mangalam: I think we are closer than many people realize, but it is important to be realistic. Science often moves in phases. Some things take much longer than expected, while others suddenly move very fast.
For diagnostics and monitoring, saliva-based tools are probably the closest to clinical application. Saliva is easy to collect, patient compliance is high, and we already see clear differences between people with MS and healthy controls. What we still need are robust longitudinal data and standardization before this can become routine.
When it comes to therapies, it is more complex. Giving single bacteria is usually not sufficient, because bacteria work as communities. What we are really aiming for is to restore missing functions and metabolic pathways, not just individual microbes. That takes time, careful testing, and regulatory approval.
My hope is that within the next five to ten years, microbiome-based approaches will start to complement existing MS therapies in a meaningful way.
Where can people follow your research activities?
Prof. Dr. Ashutosh Mangalam: The best places to follow my work are my lab website and LinkedIn. I recently updated our lab webpage, where we share our ongoing research projects, publications, and even the analysis codes we use, because transparency and data sharing are very important to us.
I’m also active on LinkedIn, where I regularly post updates about my lab, microbiome research, and topics related to MS and immune-mediated diseases. I used to be more active on Twitter, but LinkedIn is currently my main platform for science communication.
I also try to participate in podcasts and public discussions whenever possible, because I strongly believe that communication between researchers, patients, and the broader community is essential.
Final message to people living with MS
Prof. Dr. Ashutosh Mangalam: MS should not define you. A healthy lifestyle, social support, and staying positive truly matter. I have great respect for what people with MS go through every day.
From a researcher’s perspective, it is incredibly important for us to listen to patients, understand their real challenges, and work on questions that can truly improve quality of life. That is what motivates my work.
Nele von Horsten: Thank you so much, Ashu, for this insightful and hopeful conversation.
See you soon and try to make the best out of your life,
Nele
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