Neuroscientists Fight Brain Damage with Gut Microbes

Neuroscientists from Cornell University have found that by tweaking the gut microbiota of mice it’s possible to reduce the amount of brain damage incurred following a stroke.

Their work, which is described in Nature Medicine, isn’t a readymade cure for brain damage, but it does shed new light on a very hyped topic in medicine—the relationship between the gut and brain—while offering some new hope to the some 800,000 Americans who will suffer a stroke in any given year.

A stroke is a medical emergency characterized by some variety of disrupted blood flow to the brain, either by way of blockage or by way of hemorrhage. Neurons are starved of their blood supply and very quickly die. The non-fatal result is usually a combination of impaired functioning—including but not limited to cognitive deficits, hearing and vision loss, emotional and psychological problems, and, very frequently, some degree of paralysis—and, thus, permanent disability.

Functioning can sometimes be regained, at least partially, but this is by no means a guaranteed outcome. Emergency stroke interventions mostly involve removing whatever blockage is causing the stroke in the first place (a clot), usually with drugs or sometimes surgery.

The Cornell work has to do with the gut-brain coupling imposed by the immune system. Following a stroke, pro-inflammatory compounds are produced in the intestines and travel to the brain, where they cause all sorts of inflammatory trouble and ultimately facilitate brain damage beyond normal blood deprivation.

The microbes in question here are known generally as commensal bacteria. Their whole commensal thing is chilling on the parts of your body exposed to the outside world (skin, respiratory tract, gastrointestinal tract), a group of surfaces known together as the epithelium, and living it up courtesy of your various forms of filth. While often thought of as “good bacteria,” their goodness is only provisional: Good bacteria can become bad bacteria very fast if the body’s immune system goes south.

Post-stroke MRI. Image: Wiki

This immune system is represented on epithelial surfaces by Gamma delta T cells (?? T cells), which are in their highest abundance within the mucosal membranes of the intestines. Their role seems to be as a sort of early-warning system for infections and they help direct the body’s inflammatory responses. The Gamma deltas are part of the immune system’s peripheral defenses, which includes all of the immune system outside of the brain.

But they can still have effects on the brain, which is still a bit mysterious. “The peripheral immune system, which involves both innate and adaptive immune cells, has an essential role in the pathophysiology of stroke and contributes to secondary neurodegeneration by releasing neurotoxic factors, including reactive oxygen and nitrogen species, as well as exopeptidases,” the current paper explains.

So, while a stroke has the obvious effect of starving neurons of blood, there’s this whole secondary wave of destruction, which comes courtesy of the gut-dwelling Gamma delta dudes. The neuroscientists found that these cells race to the meninges, the interface between the brain and spinal cord, following a stroke, and it would thus seem that immune cells have something of a gut-brain expressway (a gut-brain axis, properly) at their disposal.

The researchers tailored the gut bacteria in their experiments using both antibiotics and fecal transplants from other mice that had been treated with antibiotics. By doing so they were able to reduce the destructive Gamma deltas while also boosting the production and transport of anti-inflammatory immune cells called Treg cells. They found that after inducing these changes, fewer inflammatory cells made their way up to the meninges, which is obviously a good thing. Less inflammation occurs in the brain, and so less destructon.

There’s still a lot of work to do here. For one thing, it’s unknown how all of this scales to human bodies and whether the effects can be replicated. We’re still a long ways off from emergency room fecal transplants for stroke patients, but at the very least we’ve learned something interesting about the immune system’s role in bridging guts and brains.