The GUT - BRAIN connection

February 11, 2022
Stress and health

If you wonder what the gut-brain connection is, chances are that you already have an idea: a “gut feeling” you might have experienced in a particular situation, feeling “butterflies” in your stomach when you have fallen in love or literally rushing to the bathroom before passing an exam. These familiar events involve very sophisticated molecular mechanisms that allow our gut (also called the ‘second brain’) to communicate with t our head and influence behaviour: what science calls the gut- brain axis.

The gut-brain axis is a communication network between the brain and the gut that exchange information in a bi-directional way (both organs are talking to and influencing each other).  This gut-brain cross-talk is done via our:

  • nervous system: mainly through the vagus nerve
  • immune system: greatly influenced by gut bacteria, inflammation, etc.
  • gut microbiota: through a variety of ‘microbial signaling molecules’. 

This communication is modulated in response to perturbations of the microbiota or the brain.

To understand the basics about how this communication works, let’s have a quick look at a few fundamental aspects of the big players in these pathways.

The vagus nerve is the longest nerve in the body, which inspired its name: in Latin the word ‘vagus’ means  literally ‘wandering’, and it’s also the root for a few other words like ‘vagabond’, or ‘divagation’. Originating in the cerebellum and brain stem, with its numerous ramifications, the vagus travels down from our head on each side of the neck near the carotid arteries, down the chest and then further down to the lower abdomen, reaching almost all the organs along the way (heart, lungs, stomach, spleen, kidney, small and large intestine, external genitalia). 

The vagus is a key component of the parasympathetic nervous system, part of the autonomic nervous system (ANS), the body's unconscious actions connecting the brain and body. While sympathetic activity is linked to our ‘fight or flight’ reaction, parasympathetic activity does the opposite: slows the body down once the stress is gone, bringing back calm and equilibrium  (homeostasis) and preparing for sitting, resting, and relaxing activities. Therefore, it will slow down the heart (decrease the resting heart rate), enhance digestion and bowel movements, favour sexual arousal etc.; the vagus is also involved in speech, eye contact, facial expressions, and more. In addition, the vagus also has an important role in the inflammation and immune response during an invasion by pathogens or tissue injury: it inhibits excessive or chronic inflammation that can be harmful for the body (“the inflammatory reflex”).

The other major player of the gut-brain connection is represented by the microbiome. The human body is the host of trillions of microscopic guests that are living in symbiosis with it: bacteria, viruses and archaea, collectively known as the microbiome. The term microbiota is used when referring to bacteria populations localised in a particular area of the body - i.e. gut microbiota, skin microbiota, mouth microbiota, vaginal microbiota, etc.). As good guests (i.e. Lactobacillus and Bifidobacterium) many of the gut microbiota populations kindly pay their rent to their human host by producing some vitamins (vitamins of group B, K, etc.), neurotransmitters (i.e. Serotonin, GABA, etc), molecules derived from dietary fiber fermentation, short chain fatty acids (SCFA), immune factors, and more  ―all called signaling molecules’. However, not all of these little guests residing in the gut are nice and beneficial; some of them can disrupt the local harmony, acting nasty to their bacterial neighbours as well as the human host, going from dysbiosis and leaky gut to potentially harmful diseases. Therefore, many studies show that there are specific modifications in gut microbiota (gut dysbiosis) in people having a variety of disorders: obesity, type 2 diabetes, cardiovascular, autoimmune diseases, Alzheimer, Parkinson, autism, depression, etc. 

So, having certain bacteria in the gut that will produce a specific network of ‘signaling molecules’  that act like local sensors will send a specific message to the brain and influence behaviour in a particular way.

For example, one of the first experiments in mice regarding the microbiome showed the relationship between gut bacteria and appetite and weight. Transferring stool from a genetically mutated mouse (the genetic mutation making them eat more) to a germ-free mouse (with a sterile gut environment since birth), caused the germ-free mice to have the same eating behaviour (an increased appetite). 

Other studies on germ-free mice show that they have an enhanced response to stress, with the deduction that microbiota influence the hypothalamic–pituitary–adrenal (HPA) axis, the main stress response system.

What’s more, gut microbiota also play a fundamental role in the immunity and inflammatory response that can influence brain function and behaviour. 

To summarise, the gut-brain axis is crucial for health and disease. Although it was originally thought that cognition and behaviour could only be regulated by the central nervous system, we now know that gut microbiota also have a big role to play.

This communication network is immensely complex and although important progress is happening in this field, there are still a lot of things to be understood and translated to clinical use. Just think of the fact that the microbial genome has in total 20 million microbial genes, and compare that to the ‘modest’ numbers of the human genome: 23,000 genes. You can imagine why we still have work in progress to understand them :) But there is a lot of hope coming from new advancements in sequencing technologies and the multi-omics field.

9 tips to improve your gut-brain connection:

  • Improve your diet: rich in fibers and nutrients and low in sugar; fermented food (miso soup, pickles, yogourt, etc.); you want to have a high diversity in your gut bacteria populations as well as optimal levels of butyrate, SCFA, neurotransmitters, vitamins (the signaling molecules that talk to your brain)
  • Prevent/control inflammation: mostly through a healthy diet (sugar is the most responsible for setting the body “on fire” with inflammation); if you have chronic intestinal symptoms, ask your doctor for help with further tests and solutions 
  • Exercise: recent studies suggest that aerobic exercise may increase gut bacteria diversity and the abundance of Firmicutes phylum that seems to protect against depression, among other things.
  • Avoid unnecessary antibiotics: especially during early life and childhood when it’s a developmental window for the gut microbiota, with future consequences for health in adulthood
  • Check your gut microbiota: ask your doctor how you can check on your gut bacteria 
  • Mindfulness: deep breathing, meditation, relaxation techniques- all these will please your vagus and your parasympathetic nervous system (for “calming down”) 
  • Massages, hugs and body therapies:will also increase the parasympathetic tonus
  • Pre- and probiotics: ideally prescribed by a professional, depending on your gut bacteria composition and your needs
  • Socialise (with humans and pets:): not only because we are social creatures (loneliness can kill us), but also because we will exchange and diversify our bacterias when we spend time in company of other people and/or pets; i.e., going to a gym will “contaminate” us with some specific beneficial bacteria found in sporty people but not in sedentary ones.


To learn more: 

Georgia Caspani et al.: Gut microbial metabolites in depression: understanding the biochemical mechanisms

Dalton A. et al.: Exercise influence on the microbiome-gut-brain axis

Dinan et al.: The Microbiome-Gut-Brain Axis in Health and Disease

Giulia Enders: Gut: The Inside Story of Our Body's Most Underrated Organ

Kim N. et al.: Mind-altering with the gut: Modulation of the gut-brain axis with probiotics

Mayer et al. : Gut/brain axis and the microbiota

Porges SW. :The Polyvagal Theory: Phylogenetic substrates of a social nervous system

Sibo Zhu et al: The progress of gut microbiome research related to brain disorders

Tamar L. et al.: Stress and the Commensal Microbiota: Importance in Parturition and Infant Neurodevelopment