Could humans have a brain microbiome?

The human gut microbiome plays a critical role in the body, communicating with the brain and maintaining the immune system through the gut-brain axis. Therefore, it is not completely unheard of to suggest that microbes may play an even greater role in our neurobiology.

Fishing for microbes

For years, Irene Salinas he 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 systems in fish to better understand how the human versions of these systems work, such as our intestinal lining and nasal cavity. The nose, he knows, is loaded with bacteria, and they are “really, really close” to the brain – mere millimeters from the olfactory bulb, which processes smell. Salinas always had the intuition that bacteria could escape from the nose into the olfactory bulb. After years of curiosity, he decided to face his suspicion in his favorite model organisms: fish.

Salinas and his team began by extracting DNA from the olfactory bulbs of trout and salmon, some caught in the wild and some raised in his lab. (Important contributions to the research were made by Amir Mani, the main author of the paper.) They plan to search the DNA sequences in a database to identify each microbial species.

These types of samples, however, are easily contaminated – by bacteria in the laboratory or from other parts of the body of a fish – which is why scientists have struggled to study this subject 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 body microbiomes. They sampled the rest of the fish’s brain, intestines and blood; they also drained the blood from the brain’s many capillaries to ensure that any bacteria they discovered resided in the brain tissue itself.

“We had to go back and redo (the experiments) several times to be sure,” Salinas said. The project took five years, but even in the early days it was clear that the fish brains were not sterile.

As Salinas expected, the olfactory bulb hosted some bacteria. But she was shocked to see that the rest of the brain had even more. “I thought the other parts of the brain didn’t have bacteria,” he said. “But it turns out my hypothesis was wrong.” The fish’s brain hosted so much that it only took a few minutes to locate the bacterial cells under a microscope. As an additional step, his team confirmed that microbes actively live in the heart; they were not asleep or dead.

Olm was impressed by his comprehensive approach. Salinas and his team approached “the same question, from all these different ways, using all these different methods — all of which produced convincing data that there are indeed living microbes in the salmon brain,” he said.

But if there are, how did they get there?

Invade the Fortress

Researchers have long been skeptical that the brain could have a microbiome because all vertebrates, including fish, do a blood-brain barrier. These blood vessels and the surrounding brain cells are fortified to serve as gatekeepers that allow only certain molecules in and out of the brain and keep out invaders, especially larger ones like bacteria. So Salinas naturally wondered how the brain in his study had been colonized.

By comparing microbial DNA from the brain to that collected from other organs, his lab found a subset of species that didn’t appear anywhere else in the body. Salinas hypothesized that these species may have colonized the fish’s brain early in their development, before their blood-brain barriers had formed. “First, everything can enter; it’s a free for all,” he said.