Tipping the balance: how might the gut microbiome influence MS?

The causes of MS are likely to be a mix of genes, something in your environment and lifestyle factors. And in recent years, researchers have begun exploring whether disruptions in the gut microbiome might play a role.

In a recent study, researchers at the University of Iowa discovered that the balance between two specific gut bacteria could predict MS severity. We spoke with lead researcher Professor Ashutosh Mangalam about his team’s fascinating work. 

What sparked your interest in studying the link between gut bacteria and MS? 

I was working in a research group studying autoimmune diseases using mouse models. My colleague found that mice with genetic changes linked to coeliac disease didn’t develop symptoms after eating gluten. This got us thinking about environmental factors like the gut microbiome. 

We transferred gut bacteria from coeliac patients to mice, expecting to trigger coeliac-like symptoms. It didn’t, but we discovered that one particular bacterium had anti-inflammatory effects. And we found that this bacterium could reduce symptoms in mice with an MS-like condition. This led to my first human MS study, where we found that people with MS had less of this bacterium. 

How might changes in the gut microbiome lead to disease? 

Diet and the microbiome are closely linked. I believe gut bacteria helped us evolve to get energy from both plant and animal food sources.   

Over time, we’ve outsourced many tasks to bacteria. To use an analogy: when I learnt to drive, I used my eyes and mirrors to change lanes. Today, my car has technology to do that for me. I recently borrowed my old car from my daughter and almost bumped into someone because I was so used to outsourcing those checks that I forgot to do them myself. That’s how I think of the gut microbiome. If we lose key bacteria we’ve come to rely on, due to diet changes, chemical exposure, or other environmental changes, this disruption can contribute to disease.  

What did your study uncover about the gut microbiome and MS? 

We first looked at whether people with MS share similar microbiomes. But we found too much variation between people. Instead, we used what we call a ‘bedside-to-bench-to-bedside' approach: studying samples from people with MS, testing our findings in lab models, then confirming them in people with MS. 

We found that people with MS had more bacteria like Blautia and Akkermansia which feed on mucin, a substance that protects the gut lining. Healthy people had more Prevotella and Bifidobacterium, which mainly digest plant-based fibres.  

We then saw the same pattern in our mice with an MS-like condition: more Akkermansia in mice with symptoms, and more Bifidobacterium in control mice. This led us to believe that the ratio of Bifidobacterium to Akkermansia might be a key marker of MS.  

We then gave the mice Blautia to see if it influenced this balance. We saw a decrease in the Bifidobacterium to Akkermansia ratio, and these mice developed more severe disease. 

We checked this finding in people with MS in both our Iowa study and the International MS Microbiome Study. In both groups, people with MS did indeed have a lower Bifidobacterium to Akkermansia ratio. A lower ratio was also linked to greater disability, suggesting it might have the potential to predict disease severity. 

Why does having more Akkermansia seem to be problematic? 

I don’t believe in ‘good’ or ‘bad’ bacteria. It’s all about context. Bifidobacterium usually keeps Akkermansia in check. But when the environment changes, for example due to stress, antibiotics or diet, Bifidobacterium struggles to survive. Akkermansia can survive solely on mucin, so it thrives.  

In good company, Akkermansia is helpful. But left unchecked, it can eat too much mucin, weaken the gut lining, and trigger inflammation. We believe this imbalance may contribute to MS progression.  

Should people with MS be taking probiotics? 

I’m sceptical about probiotics alone. Autoimmune conditions are like civil wars. Your immune system can’t tell friend from enemy. The environment is very inflammatory, so even if you introduce a ‘good guy’ like a helpful probiotic, it doesn’t have the right conditions to survive.  

That’s why we also need to create the right environment, mainly through fibre-rich, plant-based foods. We’re currently developing a capsule that combines dietary components with probiotics to increase their chances of success.  

How close are we to seeing microbiome-based therapies for MS? 

I’m hopeful. I believe that within 5-10 years doctors will be able to analyse your microbiome, open their cupboard and give you a personalised therapy to restore the balance. This approach could work alongside existing disease-modifying therapies (DMTs), enhancing their effectiveness by addressing underlying gut changes that may contribute to MS progression.  

What are the next steps in your research? What do you hope to investigate further? 

We're currently following two groups: people newly diagnosed with MS, and people who are currently in remission. We're tracking their Bifidobacterium to Akkermansia ratios over six years to see if changes can predict relapse or improvement. 

Ultimately, we want to move beyond just identifying bacteria and instead understand the networks they form. We want to understand the roles of the bacteria that are disrupted in disease. The more we understand their functions, the better equipped we’ll be to fix the problems.