This article was originally published in Quanta Magazine.
Bacteria are ubiquitous; they inhabit nearly every environment on Earth—from the depths of the ocean to the heights of the atmosphere, as well as within our bodies. For a long time, however, scientists believed that bacteria could not survive in the human brain, largely due to the formidable blood-brain barrier that is thought to shield the organ from external threats. But is it possible that a healthy human brain could possess its own microbiome?
In the past decade, research has yielded mixed results, with some studies suggesting the presence of bacteria in the brain, while others refuted it. The debate has persisted due to the challenges of obtaining uncontaminated human brain tissue suitable for studying potential microbial inhabitants.
A recent publication in Science Advances has provided the most convincing evidence to date supporting the existence of a brain microbiome in healthy vertebrates—specifically, fish. Researchers from the University of New Mexico found thriving bacterial communities in the brains of salmon and trout. Many of these microbial species have developed unique adaptations that enable them to survive in brain tissue and navigate the protective blood-brain barrier.
Matthew Olm, a physiologist at the University of Colorado, Boulder, who did not participate in this study, expressed his initial skepticism about the idea of microbes residing in the brain. However, he found the new evidence compelling. “This is solid proof that brain microbiomes are present in vertebrates,” he remarked. “Therefore, the possibility of humans having a brain microbiome should not be dismissed.”
Although fish physiology shares similarities with that of humans, there are notable differences. Nonetheless, Christopher Link, a researcher focused on neurodegenerative diseases at the University of Colorado, Boulder, and not involved in the study, acknowledged that this research adds significant weight to the notion that such microbiomes may also be relevant to mammals, including humans.
The human gut microbiome is known to play a vital role in our bodies, influencing communication with the brain and supporting the immune system via the gut-brain axis. This makes it plausible that microbes might have an even greater impact on our neurobiology.
Exploring Microbial Life in Fish Brains
For years, Irene Salinas has been intrigued by a straightforward physiological truth: the proximity of the nose to the brain. An evolutionary immunologist at the University of New Mexico, she studies mucosal immune systems in fish to glean insights into the human equivalents, such as those found in our intestines and nasal cavities. Aware that the nose is teeming with bacteria, she theorized that these microorganisms could be seeping into the brain through the olfactory bulb, situated just millimeters away. After nurturing this hypothesis for years, she decided to investigate it using fish as her model organisms.
Salinas and her team, including lead author Amir Mani, began their study by extracting DNA from the olfactory bulbs of both wild and lab-raised trout and salmon. Their goal was to identify any microbial species by matching the DNA sequences with a database.
However, such samples are prone to contamination from lab bacteria or from other parts of the fish’s body, complicating the study of this subject. If bacterial DNA were detected in the olfactory bulb, they would need to verify that it genuinely originated from the brain.
To ensure accuracy, Salinas’ team also examined the whole-body microbiomes of the fish, sampling their brains, guts, and blood, even draining blood from the numerous capillaries within the brain to confirm that any bacteria detected were indeed part of the brain tissue.
“We had to repeat many aspects of the experiments multiple times to ensure our findings were accurate,” Salinas noted. The endeavor spanned five years, but even in its early stages, it was evident that the fish brains were not devoid of microbial life.
As anticipated, bacteria were found in the olfactory bulbs, but what surprised Salinas was the higher bacterial density in other regions of the brain. “I initially thought other brain areas would be sterile,” she admitted. “But I was wrong.” The presence of bacteria was so substantial that they could be observed under a microscope within just minutes. Moreover, her team confirmed that these microbes were living and active, not dormant.
Olm praised their meticulous approach, stating that Salinas and her team thoroughly investigated the same question through various methods, all yielding compelling evidence of living microbes in fish brains.
Nevertheless, the question remains: how did these microbes arrive in the brain?
Researchers have historically questioned the existence of a brain microbiome due to the protective blood-brain barrier present in all vertebrates, including fish. This barrier is designed to permit only certain molecules to enter or exit the brain while keeping out potential invaders such as bacteria. Salinas contemplated how the brains in her research had become colonized.
By comparing microbial DNA from the brain with that from other organs, her lab identified a specific subset of species not found in other body parts. Salinas theorized that these species might have colonized the fish brains during early development before the formation of the blood-brain barrier. “In early development, anything can enter; it’s a free-for-all,” she explained.
While many of the same microbial species were also present throughout the body, Salinas theorizes that the majority of bacteria in the fish brains likely originated from their blood and guts, gradually making their way into the brain.
“After the initial colonization,” she elaborated, “specific characteristics are needed for bacteria to enter and exit.”
Salinas identified certain traits that enable bacteria to traverse the barrier, such as the production of polyamines that can open and close junctions in the barrier or specific molecules that help them evade the immune response.
She even captured an image of a bacterium crossing the blood-brain barrier, stating, “We literally caught it in the act.”
It’s possible that these microbes do not exist freely in brain tissue but are instead engulfed by immune cells. However, if they are free-living, they could play roles in the body’s processes beyond the brain, potentially influencing aspects of physiology akin to those of the human gut microbiome.
While fish are not humans, they offer valuable insights. Salinas’ findings suggest that if fish can maintain microbial life in their brains, it is conceivable that humans might too. “I am no longer surprised to find them there,” Olm remarked. “What intrigues me is whether these microbes have specific functions or if their presence is accidental.” This question not only challenges existing perspectives but also opens up fascinating avenues for understanding the role of microbes in ecosystems.
This article first appeared on QuantaMagazine.org, a platform dedicated to enhancing public understanding of science, operated independently by the Simons Foundation.
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Filed under: Bacteria, Biology, Brain, Fish, Microbes, Viruses, Nervous System.