course of antibiotic therapy can help protect mice from the ravages of a stroke in the brain, a new study shows. But before millions of stroke victims start popping the penicillin, it’s worth noting that it’s not nasty bacteria that are hurting the brain. Instead, it’s immune cells activated by those bugs.
Researchers in New York City created two groups of mice: one with gut bacteria susceptible to antibiotics, and another whose intestinal flora was drug-resistant. They exposed both groups to antibiotics for two weeks. Then, they inserted nylon wires into the mice’s cerebral arteries, reducing the blood supply and causing strokes.
Not all of those strokes were created equal, though. The resulting brain damage was 60 percent smaller in those mice whose microbiomes were affected by the antibiotics, while the mice with drug-resistant gut communities ended up with bigger holes in their brains.
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“We just changed the flora, and stroked them, and what we found was, ‘Wow! There is a pretty good protective effect,’” said Dr. Josef Anrather, a neuroscientist at Weill Cornell Medicine, who reported the findings Monday in the journal Nature Medicine.
But that doesn’t mean doctors can start prescribing antibiotics right away to reduce the amount of dead brain tissue in people who have had a stroke.
“It’s a long way from the gut to the brain, so it’s unlikely that the change in the intestinal flora could have a direct effect on the brain,” said Anrather. “There’s probably some kind of intermediary.”
That intermediary, his team reported, is the immune system. And by understanding how the immune system acts on the brain, the research could potentially change how strokes are treated. “It opens up a number of new avenues,” said Jens Nielsen, a microbiome researcher at Chalmers University of Technology in Sweden, who was not involved in the study.
And new avenues are desperately needed given the long list of once-promising drug candidates that have failed to help stroke patients.
After a stroke, immune cells are both a help and a hindrance. Some clean up the dead cells; others, however, cause inflammation — and in the brain, that inflammation can extend the wound beyond what had initially been caused by the lack of blood.
Because the gut is crawling with bacteria, it’s also full of immune cells that keep the bugs from going where they shouldn’t.
Anrather’s team made some of these immune cells glow bright green in the gut, and then traced their path through the body. They saw that some of the immune cells that make strokes worse actually migrate up from the intestines to the outskirts of the brain, bathing it in proteins that cause inflammation.
When the gut microbes were interrupted by the antibiotics, that in turn interrupted the production of these immune cells, which reduced the damage caused by stroke in the brain.
The authors still don’t know, though, what exactly proved therapeutic: the elimination of “bad” bacteria that stimulate pro-inflammatory immune cells, or their replacement with “good” bacteria that helped tamp down on that reaction.
It’s especially hard to know how this might work in humans, because our bacterial zoo contains many species not found in that of mice, and vice versa.
Nielsen is skeptical about using antibiotics to reduce brain damage. “There could be a large number of side effects,” he said. “The question is whether it’s even possible to properly target specific bacteria.”
But he suggested that figuring out the “good” bacteria could lead to the therapeutic use of probiotics.
In Anrather’s study, the researchers found that the protective effect was transferred when they took feces from the mice who had been bombarded with antibiotics, and fed extracts of it to other mice, suggesting the fecal transplants might work in humans, too.
Another more imminent possibility is to block the inflammatory proteins produced by those immune cells, a tactic already being used for certain autoimmune disorders.
If these stroke treatments make it into humans, researchers would still need to figure out at what point to administer them. After all, human strokes aren’t scheduled weeks in advance, as they were with these lab mice, so it’s up in the air as to whether an anti-inflammatory or a probiotic should be given prophylactically or as soon as possible after a stroke.
In the meantime, though, the territory of stroke neurologists just got a lot wider.
“It’s an important paper because it shows us that stroke is related not just to the brain,” said Dr. Ulrich Dirnagl, a neurologist at the Center for Stroke Research in Berlin, who was not involved in the research. “You need to talk about the gut. You need to talk about immune system.”