The human gut microbiome plays a vital role in the body, communicating with the brain and maintaining the immune system through the gut-brain axis. So it’s not entirely far-fetched to suggest that microbes could play an even more important role in our neurobiology.
Fishing for microbes
For years, Irene Salinas was fascinated by a simple physiological fact: the distance between the nose and the brain is quite small. The evolutionary immunologist, who works at the University of New Mexico, studies the mucosal immune system in fish to better understand how human versions of these systems work, such as our intestinal lining and nasal cavity. The nose, she knows, is loaded with bacteria, and they are “really, really close” to the brain, just a few millimeters from the olfactory bulb, which processes smell. Salinas always had a hunch that bacteria might escape from the nose into the olfactory bulb. After years of curiosity, she decided to confront her suspicions about her favorite model organism: fish.
Salinas and his team began by extracting DNA from the olfactory bulbs of trout and salmon, some wild-caught and others raised in his lab. (Significant research contributions were made by Amir Mani, the paper’s lead author.) They planned to search the DNA sequences in a database to identify any microbial species.
However, these types of samples are easily contaminated – by bacteria present in the laboratory or from other parts of a fish’s body – so scientists have struggled to study this topic effectively. If they found bacterial DNA in the olfactory bulb, they would have to convince themselves and other researchers that it truly came from the brain.
To cover their bases, Salinas’ team also studied the fish’s whole-body microbiomes. They sampled the rest of the fish’s brains, intestines and blood; they even drained blood from the brain’s many capillaries to ensure that any bacteria discovered resided in the brain tissue itself.
“We had to go back and redo [the experiments] several times just to be sure,” Salinas said. The project lasted five years, but from the first days it was clear that the fish’s brains were not sterile.
As Salinas expected, the olfactory bulb harbored bacteria. But she was shocked to find that the rest of the brain had even more. “I thought other parts of the brain wouldn’t have bacteria,” she said. “But it turned out that my hypothesis was wrong.” The fish’s brains harbored so many of them that it took only a few minutes to locate the bacterial cells under a microscope. As a further step, his team confirmed that the microbes were actively living in the brain; they were neither asleep nor dead.
Olm was impressed by their thorough approach. Salinas and his team circled “the same question, in different ways, using all these different methods, all of which produced compelling data that there are actually living microbes in salmon brains,” he said .
But if there are, how did they get there?
Invade the fortress
Researchers have long been skeptical that the brain has a microbiome, because all vertebrates, including fish, have them. a blood-brain barrier. These blood vessels and surrounding brain cells are strengthened to serve as gatekeepers that allow only certain molecules to enter and leave the brain and prevent invaders, especially larger ones like bacteria, from entering. Salinas naturally wondered how the brains in his study had been colonized.
By comparing microbial DNA from the brain to that collected from other organs, his lab discovered a subset of species that did not appear elsewhere in the body. Salinas hypothesized that these species might have colonized the fish’s brains early in their development, before their blood-brain barriers were fully formed. “At the beginning, anything can come in; it’s every man for himself,” she said.
