This article was originally published in Quanta Magazine.

Bacteria are ubiquitous, existing in nearly every environment on Earth, from the deepest ocean vents to the clouds above us, as well as within our own bodies. Despite their prevalence, a long-held belief among scientists is that these microorganisms cannot thrive in the human brain, as the protective blood-brain barrier typically prevents external invaders. However, could it be possible that a healthy human brain harbors its own unique microbiome?

In the past decade, initial research has produced mixed results, making this concept a subject of debate, especially considering the challenges in obtaining uncontaminated human brain samples for analysis.

Recently, a publication in Science Advances has provided the most compelling evidence to date that a brain microbiome is not only possible but present in healthy vertebrates, particularly in fish. Researchers at the University of New Mexico found diverse bacterial communities living in the brains of salmon and trout. Notably, many of these microbial species have specific adaptations that enable them to thrive in brain tissue and navigate the blood-brain barrier.

Matthew Olm, a physiologist studying the human microbiome at the University of Colorado, Boulder, and who was not part of the study, expressed his skepticism about microbes residing in the brain. However, he found the findings persuasive, stating, “This is concrete evidence that brain microbiomes do exist in vertebrates. Hence, the notion that humans might have a brain microbiome isn’t far-fetched.”

Although the physiological structures of fish and humans share similarities, key differences exist. Still, this discovery adds weight to the argument that the concept may be relevant to mammals, according to Christopher Link, who investigates the molecular aspects of neurodegenerative diseases at the University of Colorado, Boulder, and who also did not participate in the study.

The human gut microbiome plays an essential role in our overall health, influencing communication with the brain and supporting the immune system through the gut-brain axis. Therefore, it isn’t entirely implausible to consider that microbes might have even greater implications for our neurobiology.

Searching for Microbial Life

Irene Salinas has long been intrigued by a straightforward physiological observation: the short distance from the nose to the brain. As an evolutionary immunologist at the University of New Mexico, she studies the mucosal immune systems in fish to draw parallels with human systems, like our intestinal lining and nasal cavity. Aware that the nose is teeming with bacteria, Salinas theorized that these microbes might be seeping into the brain via the olfactory bulb, which processes smell. With her curiosity piqued, she decided to investigate this possibility using fish as model organisms.

Salinas and her research team, led by Amir Mani, began by extracting DNA from the olfactory bulbs of both wild-caught and laboratory-raised trout and salmon. Their goal was to identify microbial species by comparing the DNA sequences against a database.

However, these samples are prone to contamination from lab bacteria or other body parts of the fish, complicating the research. If they detected bacterial DNA in the olfactory bulb, they needed to ensure it genuinely originated from the brain.

To ensure accuracy, Salinas’ team also studied the entire microbiomes of the fish. They collected samples from various organs, including the brain, gut, and blood, even draining blood from the brain’s capillaries to confirm that any discovered bacteria were indeed brain residents.

“We had to repeat the experiments numerous times to validate our findings,” Salinas explained. The research spanned five years, but even early on, it became evident that fish brains were not devoid of bacteria.

As anticipated, the olfactory bulb contained bacteria, but Salinas was astonished to find even higher bacterial densities throughout the rest of the brain. “I assumed the other brain regions wouldn’t harbor bacteria, but I was mistaken,” she admitted. The microbial presence was so abundant that they could easily observe bacterial cells under a microscope. Furthermore, her team confirmed that these microbes were actively living rather than dormant.

Olm praised their meticulous approach, noting that Salinas and her team explored “the same question through various methods, all of which produced compelling data indicating the presence of living microbes in the salmon brain.”

Nevertheless, a crucial question lingers: how did these microbes end up in the brain?

The existence of a brain microbiome has often been doubted due to the blood-brain barrier found in all vertebrates, including fish, which is designed to restrict the entry of foreign substances like bacteria. Salinas contemplated how the brains in her study could have been colonized.

By comparing microbial DNA from the brain with that from other organs, her lab identified specific bacterial species that were not present elsewhere in the fish’s body. Salinas proposed that these bacteria may have colonized the fish brains during their early developmental stages, before the formation of the blood-brain barrier. “Initially, the environment is permissive; anything can enter,” she noted.

While many microbial species were also found throughout the fish’s body, Salinas suspects that the majority of bacteria in the fish brains originated from their blood and guts, gradually leaking into the brain.

“After the initial colonization,” she elaborated, “specific adaptations are necessary for microbes to enter and exit.”

Salinas identified certain features that facilitate bacterial passage, such as the production of polyamines that can manipulate junctions in the barrier or molecules that help the bacteria evade the immune response.

In an intriguing discovery, she captured an image of a bacterium crossing the blood-brain barrier under a microscope. “We literally observed it in the act of crossing,” she enthused.

It remains possible that these microbes do not exist freely in the brain but are instead engulfed by immune cells. However, if they are indeed free-living, they could play essential roles in the body’s physiological processes, potentially influencing aspects similar to those seen in human gut microbiomes.

Though fish are not synonymous with humans, they serve as a valuable point of comparison. Salinas’ findings suggest that if fish can sustain microbes in their brains, it stands to reason that humans might also possess such microbial inhabitants. “I’m no longer surprised to find them there,” he remarked. What truly intrigues me is whether these microbes serve a specific purpose or if their presence is merely incidental. This thought-provoking inquiry challenges our understanding of their role and opens up exciting possibilities regarding their ecological significance.

This article initially appeared on QuantaMagazine.org, a platform dedicated to enhancing public understanding of science and operated independently by the Simons Foundation.

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Filed under: Bacteria, Biology, Brain, Fish, Microbes, Bacteria, Viruses, Nervous System.