Keys to the Gut-Brain Connection

You’ve heard your gut changes your brain. Here is how.

By Austin Perlmutter, MD

The Gut Brain Axis

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For far too long, we’ve treated the brain as somehow separate from the rest of the body. We’ve acted as though what happens in our body doesn’t influence our brain biology, doesn’t change our mental health or our cognitive abilities. But now, armed with the last few decades of research, there can be no doubt that our brain and body are absolutely linked. One of the most stunning examples of the science relates to the connection between the gut and the brain, a superhighway of data that changes every aspect of who we are. Today we're exploring four of the most important systems that link our gut to our brains with a focus on some of the most recent research on this topic. From the microbiome to the gut immune system, these pathways are essential to an understanding of this powerful science.

1. The gut microbiome

The “microbiome” is the collection of all the microbes that live on and in our bodies. This includes bacteria, fungi, viruses, protists and archaea. We have a skin microbiome, a lung microbiome, and even a brain microbiome. As it relates to the gut-brain connection, almost all the emphasis is on the population of bacteria that live in our GI tract (and mainly in our large intestine). This is called the “gut microbiome,” and it’s now recognized that the makeup of these bacteria influences our mood, cognition, energy levels, and so much more. Alterations in the gut microbiome are linked to Alzheimer’s disease, Parkinson’s disease, autism, depression, anxiety and multiple sclerosis, and emerging research suggests that by modifying the gut microbiome we may gain new treatment options for these conditions. Importantly, our gut microbiome is principally programmed by environment, not genetics. This means we have agency over changing our microbes each day. For a detailed description of how we can positively influence the microbiome, check out this podcast.

2.  The enteric nervous system (aka: “second brain”)

Within the walls of your GI tract is the second largest population of neurons outside your central nervous system. These 100 million + neurons are called the “enteric nervous system,” and they play key roles in influencing aspects of gut function like regulating smooth-muscle contractions, blood flow, and secretions. Importantly, the enteric nervous system influences the gut immune system and the vagus nerve, both of which impact brain function. Alterations in the enteric nervous system are believed to help explain the connection between GI disorders like irritable bowel syndrome (IBS) and mood shifts.

3. The vagus nerve

   
   

The vagus nerve is the principal physical highway of the gut–brain axis, carrying sensory information from the gut to the brain and, in turn, conveying regulatory signals back to the digestive tract. Nearly 80 percent of its fibers are afferent (meaning they run from the gut to the brain), detecting changes in gut distension, nutrient levels, molecules that come from the gut microbiome and signals from the gut immune system, then relaying this data to a hub in the brain called the nucleus tractus solitarius. From there, signals influence brain centers involved in appetite, mood, stress responses, and even cognitive processes.

Efferent vagus nerve fibers (that run from the brain to the gut) release neurotransmitters—chiefly acetylcholine—that act on neurons in the enteric nervous system as well as gut immune cells to influence gut motility, enzyme secretion, the gut lining, and local inflammation. Mechanistically, alterations in vagus function are believed to influence multiple brain-related states, and interventions to effect change in vagus function (e.g., vagus nerve stimulation) are being studied for their role in epilepsy, long COVID, mood disorders like depression, post-stroke recovery, tinnitus, insomnia, dementia and more.

4. The gut immune system

   
   

While the exact percentage differs depending on the source, it’s nonetheless true that a major portion of your body’s immune system resides in in your GI tract where it interfaces with your food, your microbiome, your enteric nervous system, vagus nerve and your systemic immune system. The makeup and function of the gut immune system is programmed by our food and by the microbiome, but it also directly alters the microbiome through the production of various molecules like anti-microbial peptides (AMPs) which immune cells can use to limit or promote populations of certain microbes from the gut. For lots more on this topic, see this blog.

5. Other key systems and cells

   
   

There are many additional cells and signaling pathways that overlap with the above systems. For example, the enteroendocrine system produces cascades of hormones like ghrelin (which increases hunger) and GLP-1 (which increases satiety). There’s also a relatively newer discovery of the neuropod, a fascinating gut cell that directly connects to the gut’s nervous system and allows our nervous system to get real time data from the gut.

In upcoming content, we’ll explore how each of these systems interface with our health, and the tools we can use to program these pathways to promote overall, cognitive and mental health. Stay tuned!

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