The gut-brain axis (GBA) consists of bidirectional communication between the central and the enteric nervous system, linking emotional and cognitive centers of the brain with peripheral intestinal functions.

New discoveries about the gut-brain axis continue to illuminate how gut microbes affect our mood. Even after years of working on the concept, scientists are still amazed at how tiny microbes can alter the workings of the mighty human brain.

Since we can’t escape the dangerous germs coating our planet, animals have adopted their own set of beneficial microbes to fight, starve, and outcompete the pathogens. Like all important biological functions, there are backups and backups to the backups. And so, for our friendly microbes, our body has created at least three different avenues of communication.

Three different approaches to the brain

Each communication channel has its charms. Some are fast and potent, while others are gentle and languorous. If you’ve ever had food poisoning, you know about fast and potent. When your gut senses an attack of nasty microbes, you receive an urgent directive to find a bathroom, pronto. On the other hand, when you enjoy a warm bowl of oatmeal, your mood may reflect the laid-back consensus of contented gut microbes.

The three main communication channels between your brain and your gut include your nervous system, your immune system, and your endocrine system. The circulatory and lymphatic systems also play supporting roles, but these first three are dominant. Nevertheless, each system interacts with the others, making it difficult to discuss any of them in isolation. William James was right; nature is untidy.

Some of the following includes excerpts from my book The Psychobiotic Revolution that I wrote with researchers Ted Dinan and John Cryan of University College Cork, in Ireland. They are major players in the gut-brain field, and they coined the term psychobiotic to refer to microbes that can improve mood. If you are considering a deep dive into the science of the gut-brain axis, they are essential reading.

Each of the gut-brain channels has its own unique chemical language, but because they also communicate with each other, they need to have some signaling molecules in common. Here are the three main systems and the chemicals they use to chat.

The nervous system

The nervous system relays information to and throughout your brain. It communicates using chemicals called neurotransmitters. Its communication style is fast and point-to-point, but short-acting. The vagus nerve is the primary boulevard for this neural traffic.

Your gut is encased in a tube of nerves called the enteric nervous system. It contains as many nerve cells as your spinal cord, and in honor of its size and importance, it is called the second brain. A big part of its job is to control peristalsis, the rhythmic movement of muscles that squeeze your food from one end to the other. But your gut lining also contains cells that can sense the environment and send messages to the brain. These can be notices of satiety or more ominously, about pathogens and food poisoning.

Incredibly, the microbes in your gut produce neurotransmitters identical to those that your brain uses to communicate from one cell to another. These are partly for microbes to talk to each other, but also to talk to their host. The neurotransmitters include dopamine and serotonin, two of the most important chemicals involved in psychiatry. This is thus an immediate channel of communication for your gut microbes to let your brain know what’s going on down under. It can quickly alter your mood.

This gut-brain connection makes it clear why you should be solicitous of your microbial happiness. Treat your microbes right, and they will be on the front line of defense against pathogens. Abuse them, and they can make you miserable on short notice.

The immune system

The immune system is always primed to rally a defense against pathogens. It uses proteins called cytokines to signal distress. It can communicate quickly, but its urgent chemical effect can be harsh enough to cause tissue damage.

In the first 1,000 days of your life, your immune system is tasked with learning to accommodate your good gut bacteria while still remaining vigilant against pathogens. Immune cells called regulatory T cells can recognize beneficial bacteria and tamp down any attempt to destroy them. After that early education, your immune system settles down to a lifetime of fighting black-hatted germs while protecting your white-hatted good gut microbes.

However, this is situational. Beneficial microbes in your gut are tolerated, but if they breach the gut lining and gain entry into the bloodstream, your immune system will track them down and kill them. Your brain is kept in the loop on these systemic infections and may exhibit sickness behavior, which is similar to depression: you just want to be left alone to let your body heal.

Your brain is protected from blood-borne microbes by the blood-brain barrier. But if a systemic infection rages on without resolution, that barrier can weaken. If toxins or bacteria enter the brain, anxiety or even psychopathy can result. Your immune system will chase these rogue microbes into the brain, killing them but also causing collateral damage. In this scenario, your immune system can do more damage than the microbes that stimulated it.

The endocrine system

The endocrine system uses hormones to monitor and manage growth and metabolism. Its component glands communicate by secreting these hormones into your blood and thus send signals throughout the body. Its operations are slower, more moderate, and systemic, but longer acting than those of the other two systems.

The most pertinent of the endocrine systems connecting the gut and the brain is the hypothalamus, pituitary, and adrenal trio – the so-called HPA axis. The hypothalamus is always testing the blood and when it senses stress, it signals the pituitary to release chemicals that cause your adrenal glands to produce cortisol.

This stress response induces your liver to release sugar so that your muscles can spring into action and avoid a leaping leopard. When a leopard is upon us, we need instant vigor and so we steal it from a very energy-intensive part of our body: the immune system. This seems like a reasonable trade-off. First, escape the leopard, and only then do we worry about dealing with our flu.

That evolutionary response, however, is thwarted by modern-day stressors (your job, for instance) which don’t generally require either flight or fight. In fact, those can be firing offenses. We grit our teeth and bear it. And, with our immune system dialed down, we become more susceptible to infections, including gut pathogens.

In Conclusion

The gut microbiota is so important to our health, mood, and cognition that evolution has built three separate boulevards to ensure proper connections.

To optimize all three, the same advice applies:

increase your consumption of fiber (veggies and berries) and ferments (yogurt, kimchee, pickles).

There’s a caveat here if you have IBD:

fiber and probiotics can exacerbate a flare-up.

Be careful. In addition, get plenty of exercise and proper sleep. These will all improve your microbiota, which will then provide a good report to your brain, often using all three channels. A happy gut will optimize your brain, and we can all benefit from that!