▎ WuXi AppTec content team editor
Today, the leading academic journal Cell published an interesting paper online. Scientists from Cornell University have found that some of the fungi that live in the gut can actually affect the social behavior of mice! This discovery not only expands the current research on the "brain-intestine axis", but also makes us more aware that the small microorganisms that originally lived in animal bodies also have an impact on behavior.
The corresponding press release points out that the intestines perform a variety of seemingly contradictory functions at the same time — on the one hand, they absorb water and nutrients from the external environment; on the other hand, they also need to build a barrier to prevent the microbes in the intestine from invading the bloodstream and causing infection. In general, in order for the intestines to function normally, it is necessary to maintain the homeostasis of the intestines, which includes the balance of the gut microbiome. Researchers have long known that in the gut microbiome, the fungal population is an organic component. Once these fungal colonies are destroyed, it can affect intestinal function and even cause disease. However, how fungi maintain intestinal homeostasis has not been elucidated.
In mouse models, the scientists localized different fungi in the gut and found that specific fungi always accumulate near specific intestinal epithelial cells, suggesting that they may have close contact with surrounding epithelial cells. These microbes, called mucosa-associated fungi, enhance the function of mouse small intestinal epithelial cells, allowing them to avoid damage after a bacterial infection. "When we added specific fungal communities to mice, these [gut' barrier functions were enhanced." Professor Iliyan Iliev, the corresponding author of the study, said.
Interestingly, these fungi appear to be more than just maintaining the barrier function of the gut. In other experiments, the scientists found that mice carrying these fungi in their guts also showed more social behavior. In contrast, without these fungi, the mice's social behavior was less active. According to the theory of the "brain-gut axis", this may be a fungus from the intestine that gives the brain some kind of signal that changes the brain's functioning and thus behavior.
To find the farther away from the scenes, the researchers explored further and found that the key to this was a class of T cells. Under the action of fungi, these T cells secrete two immune signaling proteins: one is IL-22, which can act locally on epithelial cells and enhance the barrier function of the intestine; the other is IL-17, which can further enter the blood circulation and eventually reach the brain, acting on neurons, thus affecting the social behavior of mice.
To test this finding, the scientists did another experiment. They used a special kind of mouse that lacked receptors for IL-17 on their neurons. Even if they still carry those fungi, they do not have an impact on social behavior. This result also suggests that changes in social behavior by fungi do depend on the IL-17 pathway.
Illustration of this study (Image source: References[1])
Professor Iliev concluded that the study found a direct link between the main immune pathways and the nervous system. The former is induced by fungi in the intestine, while the latter can influence animal behavior.
Regarding the study, Professor Iliev commented that "it is a harmony, an exchange that spans two different species". In the future, the researchers also intend to focus on the other end of the "brain-gut axis", the brain, to understand how these signals affect different brain regions. One potential possibility, the press release points out, is that these gut microbes can stimulate different brain regions and immune systems, thus influencing a variety of different biological processes such as neuroinflammation regulation. Overall, this opens up a whole new area to explore.
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[1] Irina Leonardi et al., (2022), Mucosal fungi promote gut barrier function and social behavior via Type 17 immunity, Cell, DOI:https://doi.org/10.1016/j.cell.2022.01.017
[2] Preclinical study finds gut fungi influence neuroimmunity and behavior, Retrieved February 16, 2022, from https://www.eurekalert.org/news-releases/943695
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