Health Shot: Engineered probiotics for autoimmune diseases
Get the latest research on gut health, autoimmunity, chronic illness, and stress in a snapshot
Welcome to Health Shot, where we look at the newest research related to gut health, autoimmunity, chronic illness, stress, and the relationship between them.
Today’s study: Scientists show that engineered probiotics can reduce MS symptoms in mice
Probiotics are, if you have any kind of gut issue or autoimmune disease, at once a beacon of hope and a morass. If I were to flippantly summarize Ed Yong’s seminal book on the incredible relationships that exist between microbes and animals, I Contain Multitudes, it would be: microbes are all-powerful and we still don’t understand shit (pun intended) about how they work in the human gut so good luck trying to actually use them to treat anything right now.
However, being at the early stages of research into probiotic treatments for disease is also exciting and hopeful. It means that we are in for a lot of discoveries and new, more effective microbe-based therapies for diseases that we have or will develop. That is cool.
Research overview
A new lactate-producing probiotic is shown to reduce brain and spine inflammation in mice
In a new study published in Nature last week, a team from Harvard looked at whether they could engineer probiotics to manage the progression of multiple sclerosis (MS), one of the most common autoimmune diseases.
The team investigated causes of inflammation in the brain and spinal cord, a hallmark of MS. They found that there is a specific metabolic pathway that limits inflammation, and that pathway is driven by the production of a metabolite called lactate. In other words, in the presence of lactate, a chain of events occurs within the body that serves as a brake for central nervous system (CNS) inflammation.
This was a key finding, lead researcher Francisco Quintana told me via phone this week, because it suggested a mechanism for limiting CNS inflammation. “Our reasoning was: maybe we can engineer a probiotic to produce lactate as a way of activating this brake on the immune system, and hence as a way of limiting inflammation.”
That’s just what they did. The team engineered a strain of E. coli to produce lactate. They found that, by giving these engineered microbes to mice with MS-like symptoms, they were able to reduce brain and spine inflammation.
Gut-Brain connection
Over-the-counter probiotics aren’t strong enough to impact an existing disease state, but engineered probiotics show early signs of effectiveness
Previous research by this team and many others has demonstrated that the key components of the immune system in the brain that cause inflammation are activated and educated in the gut. That’s why the team suspected that altering metabolites in the gut could impact inflammation in the brain.
They chose to work with E. coli because it is a bacteria that naturally occurs in all of our guts, and the E. Coli strain they selected has a long history of use as an anti-inflammatory probiotic. There are naturally occurring lactate-producing bacteria, like those found in over-the-counter probiotics, but in the case of a system with a lot of existing inflammation, the effects of those bacteria would be too weak.
“You need to arm them up to be strong enough to deactivate ongoing inflammation,” Quintana said, “to deactivate ongoing hyperactive disease mechanism.”
Showing that these souped up microbes in the gut can impact inflammation in the brains of mice furthers the evidence that inflammation throughout the body can often be traced back to the gut.
Beyond MS
Potential IBD, diabetes, and arthritis implications
This finding is particularly exciting because the anti-inflammatory mechanism involving lactate is universal, not just applicable to the CNS. The team has done previous research around IBD, and is already collecting data on effects of the same lactate-producing engineered probiotic applied to mice with irritable bowel syndrome. In fact, they started with the brain because it is one of the furthest organs from the gut, and obviously one of the most important in the body. If they can impact the brain, they reasoned, they can likely impact other organs. Now the team aims to look at curbing inflammation in the pancreas, important in diabetes, and joints, which become inflamed with arthritis.
They are in the process of creating a company around their work to fund the first human trials of their engineered probiotics. It’s a long process, but one we will be following!
What do you think…
Would you ever consider taking engineered probiotics?
Another great new format in your research writing, Rae. Health Shots! You are translating the medical research domain with a personal investment that is very powerful. I love what you’re doing.
as a neurodivergent (formerly bipolar) person with food sensitive also recovering from SIBO, this is like... as familiar as it is hopeful? inflammation will get you every time.