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The Secrets of Your Gut-Immune-Brain Connection

These science breakthroughs are absolutely incredible!

By Austin Perlmutter, MD



  • Your gut may influence most aspects of your health

  • The gut microbiome and your other gut cells are known to impact brain health

  • One powerful pathway connecting your gut to your brain is your immune system

  • The gut, including the bacteria within it, seem to speak directly and indirectly to our immune system, which then impacts brain health

  • Strategies to improve gut health may have positive effects on immune balance and brain wellness

Right now, deep in your GI tract, you’re harboring tens of billions of bacteria that break down your food, produce neurotransmitters and other bioactive molecules and influence how you think, feel and function. The dance between your cells and these gut bugs has captured the interest of top scientists and the general public around the world, and for good reason. It’s thought that the makeup of the bacteria in our gut (part of what’s called the “gut microbiome”) impacts overall health and even happiness. But how is it possible that your gut bacteria can impact your brain? One way is by the immune system. Here’s how it all comes together.

Like the gut microbiome, your immune system exists in a complex network of cells and signals.

Recent research shows that red blood cells play a key role in the immune response, which means that about 90% of the cells in your body are immune cells (over 30 trillion!). Our immune system is tasked with the delicate balance of defending us against the environment (for example, fending off an infection) while not going overboard and causing unnecessary damage our own tissues (e.g., autoimmune disease).

Most white blood cells and immune tissue in our bodies are housed in the gut, where they learn from and respond to data flowing from our food and our gut microbiome. Other immune cells are located in our lungs and skin, along with our livers and basically every tissue in our bodies (including our brains). We now know that by altering the state of our immune system, by way of signals sent out into the bloodstream and even by way of the vagus nerve (which runs from the gut to the brain), our gut has a say in how our brain functions.

The exact pathways linking our gut with our immune system are complex and myriad. As a few examples:

  • Gut bacteria can form products called endotoxins that may increase inflammation in our bodies

  • Gut bacterial composition and food in the gut may directly alter the makeup of the gut immune system

  • Gut molecules, including those made in response to food and by the gut microbiome alter vagus nerve signals to the brain

Once the immune system is altered by the gut, how does this impact our brain health? Again, this is complex science. Here are a few important pathways:

  • Inflammation created by gut bacterial breakdown products may enhance brain inflammation and increase risk for brain diseases

  • Molecules created by bacteria (e.g., short-chain fatty acids) may influence brain wiring and growth of new neurons

  • Immune signals detected by the vagus nerve send data up to the brain that may alter brain function

  • Pieces of broken down gut bacteria may damage the blood brain barrier, increasing brain exposure to unhelpful molecules from the blood

What does all this mean practically?

Despite a number of articles, social media posts and even books that attempt to make topics like the gut-brain connection and the immune system seem simple (and then offer quick-fix solutions) it’s important to realize that these are very nuanced and complicated topics in science. With this said, prioritization of gut health may also enhance immune balance as well as brain state. To this end, some of the more substantiated strategies include:

  • Eat a diversity of whole plant foods (especially fruits and vegetables)

  • Prioritize dietary fiber sources

  • Minimize consumption of ultraprocessed foods

  • Consume more colorful fruits and veggies, as well as spices and herbs, coffee and teas rich in polyphenols (plant nutrients)

  • Minimize unnecessary exposure to antibiotics

  • Reduce added sugar (and sugar alternative) consumption

  • Limit excess alcohol consumption

  • Mitigate excess or chronic stress when possible

  • Consider including fermented foods in your diet (e.g., kimchi, sauerkraut)

  • Exercise regularly

  • Prioritize quality sleep

As a final reminder: everyone’s gut, immune system and brain is unique. If you’re worried about gut issues, immune issues or brain issues, speak with your health practitioner to find strategies best tailored to your personal needs.

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