The researchers found that the antibodies are constantly being produced in the brain sinuses instead of only at the time of infection.
It is a well-known fact that the gut and the brain are closely connected with each other. Anything that happens in the brain (stress and anxiety for example) has a tendency to affect the gut and the gut sends signals to the brain when it is distressed.
Now, a group of researchers at the National Institute of Health (NIH) and Cambridge University say that it is the gut microbes that train your immune system to protect your brain from infections.
The findings of the study are published in the journal Nature.
The brain layers and immune system
Our brain is surrounded by three membranes called meninges that are constantly at war with harmful microbes to protect the brain. It is also surrounded by blood vessels that are sealed by the blood-brain barrier, which is a semi-permeable membrane that only selectively allows solutes to pass through.
However, the outermost membrane called dura mater has large sinuses that return slow-moving blood to the heart. These open spaces and their closeness to the brain makes the dura mater vulnerable to pathogens.
Previous studies have shown the presence of macrophages (cells of the innate immune system) and T cells inside the brain.
The latest study was done using mice and human autopsy tissues.
Looking at the dura mater, the researchers now found IgA antibodies inside the dura mater, something that has never been noted before. IgA is a type of antibody that is present in various secretions of the human body including tears and mucous.
To study the effects of the microbiome in this protection, the researchers compared normal healthy mice to germ-free mice (without their own microbiome) and found that the latter had almost no IgA in their meninges. On reconstituting the gut microbiota of the germ-free mice with microbes that can only stay in the gut and not move around, the researchers found that the IgA repertoire in the meninges was completely reconstituted.
The same did not happen on reconstructing the skin microbiota of these mice, suggesting that it is the gut microbes that play a role in the IgA immunity in the brain.
The DNA of the IgA antibodies in the meninges and a section in the intestine was found to have a 20 percent similarity, indicating the same source for both. On breaching the intestines artificially in the lab, an immune response was seen in both the gut and meninges, further confirming the link.
Finally, to study the role of IgA in protecting the meninges, the researchers introduced a fungus inside the meninges of two groups of mice — normal healthy ones and ones with depleted IgA due to gene manipulation. They noted that mice with a healthy immune system did mount a strong IgA response against the fungus. However, mice who did not have enough IgA got the fungal infection in their brain and died.
Interestingly, the researchers found that the antibodies are constantly being produced in the brain sinuses instead of only at the time of infection. However, administration of antibiotics reduced IgA in the meninges of mice, suggesting that even a temporary reduction in microbes in the body can affect the immune system.
For more information, read our article on Immune system and immunity.
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