The human gut microbiome plays a key role in the body, communicating with the brain and maintaining the immune system gut-brain axis. So it’s not entirely far-fetched to suggest that microbes may play an even greater role in our neurobiology.
Fishing for microbes
Over the years Irena Salinas was fascinated by a plain physiological fact: the distance between the nose and the brain is quite diminutive. An evolutionary immunologist at the University of Recent Mexico is studying the mucosal immune systems of fish to better understand how human versions of these systems, such as the intestinal mucosa and nasal cavity, work. He knows that the nose is full of bacteria that are “really, really close” to the brain – just millimeters from the olfactory bulb that processes smell. Salinas always had a hunch that bacteria could travel from the nose to the olfactory bulb. After years of curiosity, she decided to confront her suspicions with her favorite model organisms: fish.
Salinas and her team began by extracting DNA from the olfactory bulbs of trout and salmon, some wild-caught and others bred in her lab. (Amir Mani, lead author of the article, made an significant contribution to the research.) They planned to check DNA sequences against a database to identify any microbial species.
However, these types of samples can be easily contaminated – by bacteria in the lab or from other parts of the fish’s body – so it is tough for scientists to study the topic effectively. If they did find bacterial DNA in the olfactory bulb, they would have to convince themselves and other researchers that it actually came from the brain.
To explore their base, Salinas’ team also examined the fish’s whole-body microbiomes. They took samples of the remaining fish brains, entrails and blood; they even sucked blood from many of the brain’s capillaries to ensure that any bacteria they discovered were within the brain tissue itself.
“We had to go back and repeat [the experiments] many, many times, just to be sure,” Salinas said. The project took five years, but it was clear from the beginning that fish brains were not sterile.
As Salinas expected, there were bacteria in the olfactory bulb. But she was shocked to see that the rest of the brain had even more. “I thought there were no bacteria in other parts of the brain,” she said. “But it turned out that my hypothesis was wrong.” There were so many fish brains that it took only a few minutes to locate the bacterial cells under a microscope. As an additional step, her team confirmed that microbes actively live in the brain; they weren’t dormant or dead.
Olm was impressed by their thorough approach. Salinas and her team asked “the same question in different ways, using different methods, and each of them provided compelling data that there are indeed live microbes in the salmon brain,” he said.
But if so, how did they get there?
Invasion of the Fortress
Scientists have long been skeptical that the brain could host a microbiome because all vertebrates, including fish, have blood-brain barrier. These blood vessels and the brain cells surrounding them are strengthened to serve as gatekeepers that let certain molecules in and out of the brain and keep out invaders, especially larger ones like bacteria. So Salinas wondered how the brains in her study became colonized.
By comparing microbial DNA from the brain with DNA taken from other organs, her lab discovered a subset of species that did not appear elsewhere in the body. Salinas hypothesized that these species may have colonized the fish’s brains early in development, before their blood-brain barrier was fully formed. “In the beginning, anything can come in; it’s free for everyone,” she said.