The human gut microbiome plays a fundamental role in the body, communicating with the brain and maintaining the immune system through the gut-brain axis. Therefore, it is not entirely unreasonable to suggest that microbes could play an even greater role in our neurobiology.
Fishing for microbes
For years, Irene Salinas He has been 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 mucosal immune systems in fish to better understand how human versions of these systems, like our intestinal lining and nasal cavity, work. She knows that the nose is loaded with bacteria, and they are “very, very close” to the brain, just a few millimeters from the olfactory bulb, which processes smell. Salinas has always had a feeling that bacteria may be leaking from the nose into the olfactory bulb. After years of curiosity, he decided to confront his suspicions in his favorite model organism: fish.
Salinas and his team began by extracting DNA from the olfactory bulbs of trout and salmon, some caught in the wild and others raised in his lab. (Amir Mani, the lead author of the paper, made important contributions to the research.) 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 in the laboratory or from other parts of a fish’s body), which is why scientists have had difficulty studying this topic effectively. If they found bacterial DNA in the olfactory bulb, they would have to convince themselves and other researchers that it really originated in the brain.
To cover their bases, Salinas’ team also studied the fish’s whole-body microbiomes. They took samples of the rest of the brain, guts and blood of the fish; They even drained blood from the brain’s numerous capillaries to ensure that any bacteria they discovered resided in the brain tissue itself.
“We had to go back and redo (the experiments) many, many times just to be sure,” Salinas said. The project lasted five years, but already in the first days it was clear that fish brains were not sterile.
As Salinas expected, the olfactory bulb harbored some bacteria. But he was surprised to see that the rest of the brain had even more. “I thought the other parts of the brain wouldn’t have bacteria,” he said. “But it turned out that my hypothesis was wrong.” The fish’s brains contained so much that it only took a few minutes to locate bacterial cells under a microscope. As an additional step, his team confirmed that the microbes were actively living in the brain; They were neither asleep nor dead.
Olm was impressed by his thorough approach. Salinas and his team circled “the same question, in all these different ways, using all these different methods, all of which produced compelling data that there are actually living microbes in the salmon brain,” he said.
But if there are, how did they get there?
Invading the fortress
Researchers have long been skeptical that the brain has a microbiome because all vertebrates, including fish, have a blood-brain barrier. These blood vessels and surrounding brain cells are strengthened to serve as gatekeepers that allow only a few molecules to enter and leave the brain and keep invaders away, especially larger ones like bacteria. So naturally, Salinas wondered how the brains in his study had been colonized.
By comparing microbial DNA from the brain with that collected from other organs, his lab found 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 their development, before their blood-brain barriers had fully formed. “From the beginning, anything can come in; “It is a pitched battle,” he said.