Chronic Pain and the Gut Microbiome

The Brain-Gut Microbiome System
There are trillions of microorganisms (bacteria, archae, fungi, and viruses) living in our gut, making up the gut microbiome. They not only interact with each other but communicate with the gut and the brain through different cell types and sensors, nerve cells, immune cells, and hormone-producing cells. The microbial organisms are not only similar in total numbers to our human cells, but their gene pool greatly surpasses the number of our human genes!

This brain-gut microbiome (BGM) interaction goes in both directions: the microbes produce signaling molecules that act on the different cell types and receptors in the gut, and the gut releases molecules – such as serotonin, norepinephrine, and dopamine – that talk back to the microbes and influence their behavior as well as their interactions with the host.

The Wisdom of the Gut Microbiome
Microbes are the oldest and most abundant life forms on the planet. They have spent billions of years in the planet's oceans, developing an incredible, sophisticated intercellular communication system. Their shared biological language has allowed them to talk to each other and communicate with their environment – and with our gut and brain – in unparalleled ways. Tapping into the wisdom stored in millions of microbial genes, gut microbes can rapidly adapt to different habitats and develop synergistic relationships with their hosts.

Even though the interactions of microbes with their hosts started with very primitive marine animals hundreds of millions of years ago, if you look at any animal on this planet today – bees, cockroaches, elephants, giraffes, humans – you will find microbes living in symbiosis with their guts.

The large intestine has the highest number and concentration of microbial organisms of any place on the planet – some 40 trillion – almost as many human cells as our bodies contain. These organisms contain over a hundred million genes, severalfold the amount of our mere 20,000 human genes. So, gut microbes clearly know to whom they're talking, and they know what messages and signals are best for the animals that are their hosts.

How the Gut Microbes and the Brain Communicate with Each Other
There are four major communication channels through which the gut microbes communicate with our brains. This communication is made possible by the ability of certain gut microbes to break down various components in our diet into absorbable molecules, so-called metabolites. Using these molecules, gut microbes can signal to the brain via the vagus nerve through systemic circulation.

Communication can also happen via molecules that involve the immune system. At the same time, the brain can influence microbial behavior via the autonomic nervous system. This can involve the stress mediator norepinephrine acting on microbial receptors, or it can result from a change in the habitat of microbes through stress-induced changes in gut motility and secretion.

Microbial cell membranes contain molecules that interact with special receptors on immune cells called “Toll-like receptors.” Such interactions are normally prevented by the intestinal barrier, made up of the intestinal wall and a thick mucus layer. If this barrier is compromised by chronic stress or an unhealthy diet – a situation referred to as “leaky gut” – sensory immune cells come in contact with the microbes in the gut. The immune cells don’t care if the contact is made by good microbes (so-called commensals) or by pathogens that can cause infections. Once the microbes come in contact with the gut’s immune cells, they activate them to release inflammatory substances – the cytokines – which can lead to low-grade inflammation in the gut, in our blood, and in the brain.

The Clinical Implications of the Gut Microbiome
Microbiome science has revealed remarkable insights during the past decade. This has led to a paradigm shift in our understanding of the importance of the gut microbiome for many aspects of our health and in the possible causal involvement of gut microbial alterations in several chronic diseases, including cancer, diabetes, neurodegenerative disorders, and chronic pain.

Even though a causal role of the gut microbiome in chronic pain has not been established, there are several plausible hypotheses of how this may occur. While diet and mindfulness strategies are currently the most effective ways to normalize the communication between the gut microbiome and the brain, future strategies will involve so-called second-generation probiotics and genetically engineered microbes.

Register for CHYP's May Webinar scheduled for May 21 at 10 a.m. PT, where Dr. Mayer will discuss “The Gut Microbiome: Why Those ‘Buggers’ Are Important in Emotions and Chronic Pain."