Microbial inputs in the early stages of life are very important. Certain types of bacteria and pathogens induce inflammation in the body which itself can have downstream effect later in life. Some bacteria have been seen to have evolved or co-evolved that they are able to induce anti-inflammatory or immuno-regulatory responses.
Part of the hygiene hypothesis dictates that by moving from farms to rural areas or cities, unfortunately aided us to lose contact with those types of bacteria that serves their ecological service. This creates an imbalance which creates failure of immunoregulation in the gut that can persist for years.
People that grow up in places with diverse microbial environment respond differently to the psychosocial stressors compared to those who live somewhere else. These people had reported feeling more anxious and stressed unlike those living in the cities with no pets who had massive exaggerated inflammatory response to the stressors in their environment.
One of the two types of neuro-connections that allows this bi-directional communication which is the Vegas nerve which innervates the GI tract and the brain’s communication.
The amount of vegetables and fruits an average person eats in a week significantly paired with reduction of junk food intake creates a higher diversity of the gut microbiome. This shows significant reduction in depressive symptoms.
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A fat molecule coming from a bacterium that originates in the soil that when taken up by an immune cell shuts off, takes over the molecular machinery of that immune cell and shuts off the inflammatory cascade. And we think this is a product of hundreds of millions of years of coevolution of bacteria and mammal and that this relationship between bacteria in mammals including humans is incredibly important for our physical health, and our mental health.
Our lab has been interested in approaches for prevention, not only treatment of psychiatric disorders, but also prevention. We should start thinking about prevention strategies for psychiatric disorders. And if this is one of our goals, where should we start? We should start by considering what the risk factors are and are there risk factors that we can impact in a way that would reduce the risk for developing psychiatric disorders. And so, known risk factors for psychiatric disorders include, genetic predisposition but also, environmental influences and interactions between genes and environment.
This is how we think this works. Here we’re talking specifically about bacteria that we think drive immunoregulation and production of anti-inflammatory cytokines. Graham rook coined the term old friends, but these are the organisms that can drive this immunoregulation that keeps inflammation under control. The same organisms that we think we have reduced exposure to when we move into an urban environment. What they have the capacity to do, these old friends, is bind to receptors on what are called immature dendritic cells a type of immune cell that’s part of our innate immune system that causes these dendritic cells to mature into regulatory dendritic cells, the bias the differentiation of naive T-cells into regulatory T-cells that have this anti-inflammatory function. So these old friends, these bacteria are biasing the immune system in a way that results in anti-inflammatory responses and protection from chronic inflammation.
There are two types of neural connections, general categories that allow this bi-directional neural communication. One you may have heard of, which is the Vegas nerve which innervates the gastrointestinal tract. it has thousands and thousands of nerve fibers in the Vegas nerve, some of those are going from the brain, to the gut, and some are going from the gut, to the brain. And so that’s what we’re talking about when we refer to this bi directional communication.
We also think the microbiome is very important in post-traumatic stress disorder. Our clinical trials that we’re conducting at the VA are individuals with post-traumatic stress disorder. But here we have, by definition, the involvement of trauma. Of course, we know from earlier toxic trauma is also an important risk factor for depression but this is a diagnostic criterion for PTSD. And many of the same mechanisms that are involved in the relationship between the microbiome and this bi-directional microbiome gut brain axis are also we believe important in PTSD.
Psychiatric disorders associated with decreased regulatory T-cells that didn’t show the data for that but we know that’s the case. Decreased immunoregulation and increased inflammation, and microbiome-based interventions to prevent anti-inflammatory immunoregulatory signaling to increase anti-inflammatory immunoregulatory signaling might be considered for prevention and treatment of psychiatric disorders.