The Mind-Gut Connection: How the Hidden Conversation Within Our Bodies Impacts Our Mood, Our Choices, and Our Overall Health

by Emeran Mayer

comprises 1,000 times more cells than exist in your brain and spinal cord, and ten times more than the number of human cells in your entire body. Together, the gut microbiota weigh about as much as your liver, and more than your brain or your heart. This has led some people to refer to the gut microbiota as a newly discovered organ, one that rivals the complexity of your brain.

The symbiosis between the microbes and their hosts that developed in its simplest form millions of years ago continues in our bodies today.

They also gain a free connection to our internal Internet traffic—the constant flow of information transmitted by hormones, gut peptides, nerve impulses, and other chemical signals. This information allows them to keep track of our emotional states, our stress levels, whether we are asleep or awake, and which environmental conditions we are exposed to.

In exchange, the microbes provide us with essential vitamins, metabolize digestive compounds, called bile acids, that are produced by the liver, and detoxify foreign chemicals that our bodies have never experienced—so-called xenobiotics.

The amount of information that is allowed to travel through this system depends in large part on the thickness and integrity of the thin mucus layer lining the gut surface, the permeability of your gut wall (its leakiness), and the blood-brain barrier.

Normally, these barriers are relatively tight, and the flow of information

from gut microbes to the brain is restricted. But stress, inflammation, a high-fat diet, and certain food additives can m...

One means of communication involves specialized immune cells known as dendritic cells,

Dendritic cells have “tentacles” that extend into the gut’s interior, where they can communicate directly with the group of gut microbes that live near the gut wall.

when harmful or potentially dangerous bacteria are detected through these mechanisms, they trigger an innate immune response—a cascade of inflammatory reactions in the gut wall—to keep the pathogens in check.

When microbes penetrate the protective mucus layer that covers the lining of the gut, the molecules of their cell walls trigger the activation of immune cells beneath the gut lining, which then tailor the immune response depending on whether, or to what degree, the microbe poses a danger.

LPS—is

a component of the cell wall of certain microbes called gram-negative organisms, is able to increase the leakiness of the gut, thereby facilitating the ...

when inflammation, stress, or excessive dietary fat has compromised the two natural barriers that keep us separated from the trillions of microorganisms in our gut lumen, the gut microbes or their signaling molecules can cross the gut lining in greater numbers, causing even greater engagement of the gut-based immune system, an inflammatory process that can spread throughout the body.

This process has been referred to as metabolic toxemia.

the gut’s immun...

responds by producing a number of mol...

cytok...

these cytokines can cause local full-blown inflamm...

Alternatively, cytokines may spill into the bloodstream, travel to the brain like a hormone, transverse the blood-brain barrier, and activate immune cells—called microglial cells—inside the brain.

Such long-distance immune signaling from the gut to the brain has been implicated in the development of neurodegenerative diseases such as Alzheimer’s.

Gut microbes

produces several hundred thousand different metabolites,

make it into the bloodstream, where they account for nearly

40 percent of all circulating molecules.

Many are considered ne...

Once in the circulation, the metabolites can then travel to many organs in your body, including the brain, as a hormone does.

Another important way microbial metabolites signal the brain is via the serotonin-packed enterochromaffin cells in your gut wall.

They can also alter your sleep, pain sensitivity, and overall well-being.

gut microbes constantly adapt to regional shifts in acidity, secretion of vital digestive fluids, available nutrients, and how much time they have to digest them before they’re excreted.

when stress or high anxiety causes the brain’s emotional operating programs to create dramatic plots that play out in our guts, it alters gut contractions,

We now have solid evidence that stressful experiences in early life, including a compromised interaction between the primary caregiver and his or her child, can leave lasting traces on his or her offspring’s brain.

In order to develop novel therapies aimed to reverse this early programming in patients, we needed to know how our earliest experiences alter specific neural circuits in our brains that underlie our response to a variety of stressful situations.

His research team took genetically identical rat mothers and videotaped and analyzed their behaviors while the pups were infants. Then they let the pups grow up, and checked how the pups of nurturing rat moms fared compared with the offspring of stressed-out moms.

The pampered pups grew into adults that were more laid-back, less reactive to stress, and less prone to addictive behaviors, such as overdoing it when given a free supply of alcohol or cocaine. They were also more social with other rats, more daring, and more willing to explore new places.

Pups of stressed, negligent moms grew into loners prone to the rat equivalents of anxiety, depression, and addictive behaviors. Studies of monkey moms an...

These early findings were the beginning of a paradigm shift in our understanding of how experiences in childhood can affect our health and the dialogue between the gut and the brain.

a large body of scientific evidence has accumulated that confirms the close relationship between a mother’s stress level and the way the nervous system of the child will react to stress later in life.

Whole brain circuits and connections developed differently depending on the mother’s behavior, and several neurotransmitter systems involved in these connections were altered.

When we stressed mother rats by separating them from their pups for three hours a day during the first weeks of life, as Plotsky had, the pups later showed many

IBS-like features.

In our experiments, the rats that had experienced a less nurturing

childhood presented with similar traits. The animals were more anxious, their intestines were more sensitive, and when stressed they would excrete more small stool pellets, the rat equivalent of diarrhea.

We had demonstrated for the first time in humans that our brains become rewired in response to adverse experiences early in life—and that rewiring can persist throughout our lifetime.

epigenetic,

Poor mothering altered just a few of the bookmarks and highlights. But some of the tagged genes altered brain signaling, which made the adult daughters poor mothers themselves. This caused their own pups to tag their genes, and the cycle continued.

in genetically identical twins there was a higher likelihood that both twins suffered from IBS symptoms, compared to such concordance in dizygotic twins.

Levy also found that having parents with a diagnosis with IBS was a stronger predictor of an IBS diagnosis in their children than having a twin with IBS.

mechanisms other than genes play a crucial role in the intergenerational transmissi...

plausible that epigenetic mechanisms also play an important role in explaining the common family history of stress...