How and Why Gut Bacteria Influence the Brain

As soon as individual cells evolved into large multicellular organisms during the Cambrian period about 500 million years ago, bacteria discovered the fantastic survival benefits of fully integrating themselves into every biological space available. They never left. The total weight of the many trillions of bugs that reside in your gut is over two pounds and they are multiplying constantly thanks to all the nutrients with which you constantly provide them. Your gut bacteria need those nutrients because they are in a constant battle for survival. The viruses in your gut kill so many bacteria every minute that their carcasses account for about 60 percent of the dry mass of your feces. (Now you know what is in there.)

The bacteria that have hitched their fortunes to you contribute to your good mental health as well as to your illnesses. As our species and theirs evolved, we established some rules to govern our symbiotic cohabitation, and most of the time everything works out well. Bacteria contribute over 50 percent of all of the proteins that float around in your blood. Without these proteins, we would not survive long. But like an unpredictable roommate, these bugs can turn against us or allow unwanted guest bacteria to take up residence. It is widely accepted that the balance of different bacteria in one’s gut significantly influences your physical and mental health in general and may underlie the development and maintenance of mental illness.

One recent study collected fecal samples from subjects (aged 18–65) meeting the DSM-5-defined criteria for Bipolar Depression. Their data were compared to age- and sex-matched healthy controls without current or past history of mental or major medical disorders. Their results suggest that patients with Bipolar Depression have a distinct gut microbiota profile with a lesser abundance of Clostridiaceae and a higher abundance of Collinsella bacteria, as compared to healthy controls. In addition, patients with Bipolar Depression, relative to healthy controls, had a decreased diversity within their gut community. A loss of microbiome diversity is also associated with autism spectrum disorders.

Such a lack of bacterial diversity is believed to play a critical role in multiple chronic medical disorders. Clostridiaceae is a relatively large bacterial family containing more than 30 genera. The diversity of organisms within the Clostridiaceae family makes it difficult to identify specific mechanistic pathways that may link the abundance of this Clostridiaceae to disease states. Collinsella was observed to be more abundant in Bipolar type II patients when compared with Bipolar type-I patients. Despite its abundance in the human gut, little is known about its role in human health and disease.

The balance of bacteria has been observed to alter the inflammatory environment of the gut and subsequently of the blood. Some pathogenic gut bacteria release significant amounts of the cytokine TNF-alpha into the blood that can easily enter the brain. At high levels, this cytokine in the brain can impair brain function and cause neuronal death. Gut bacteria also release other proteins into the blood that can influence mood. One recently-discovered protein, queuine, can alter the production of the neurotransmitters dopamine and norepinephrine in the brain. Another chemical, called an endozepine, acts similar to the drug valium and can influence anxiety levels. A deficiency in this endozepine may underlie chronic anxiety disorders.

Obviously, we have much to learn about our ancient relationship with these tiny creatures who have become so important for our survival and happiness.

© Gary L. Wenk, Ph.D.