When we think of sensory experiences, we think of sights, sounds and smells; touching and tasting. Seldom do we think of the vast amount of sensory information encoding that occurs somewhat removed from our five senses: inside of our gut.

I was surprised when I first learned about how important a role the gut plays for our direct interactions with the environment. Since researching this a little more I've become absolutely fascinated by the exciting research questions that surround the topic. These questions are of interest, not only to Neurogastroenterologists who study digestive systems (and whom I imagine must be generally skilled at spelling ridiculously long words), but also to Cognitive Scientists trying to understand the brain, Psychologists studying depression, and even Economists -like myself- researching human decision making.

While proverbial butterflies in our stomach and presidential gut decisions may be linguistic indication of an intuition that certain emotional states and behaviors may originate in the abdomen rather than the head, to most people the hard fact that our gut houses a nervous system so very similar to the brain in the way it encodes and signals information about the environment that it has been referred to as the second brain, can be alienating (read: freaked me out). Yet, at closer consideration the gut does quickly reveal itself as an optimally suited location for any organism developing a complex system for gathering and processing environmental information:

Consider first the basic dimension of surface area available for interacting with environmental substances. By folding intricately, (but most of all often) the gut achieves an internal surface area that is about 100 times larger than the surface area of our skin. All of this surface area is in constant contact with what would technically be labeled environment, if you're willing to concede that simply swallowing something is not enough to make something truly part of your body. Instead, actual absorption and assimilation into the body, requires that entering substances are broken down and subsequently transported through the walls of our internal organs. Generally speaking such is the basic responsibility of the nervous system in our gut: Most of what it is utilized for relates directly to digestion and determining the passage of substances into our bloodstream.

Since aspects of these fundamental gut responsibilities are immune related, it may not come as a surprise then to find that roughly two thirds of the body's immune cells are in fact located in the gut.

Add to these body-own immune cells the activity of some 100 trillion microorganisms (about 40K species, with about 100 times the amount of genes than are present in the human genome), and one quickly grows comfortable with the gut's moniker as the body's largest immune system.

Returning to the idea of a second brain however, the most impressive property of our gut in this context might be the lavish number of neurons located inside of it: The number of neurons - our body's electro-chemically excitable signal transmission cells - located inside the gut lies between 200 and 600 million. These numbers (and the admittedly wide range) are put into perspective by considering that they amount to basically the same number of neurons as are located in the spine.

This truly vast amount of neurons, together with the mentioned majority of our immune cells, and the so called enteroendocrine cells which secrete most of our digestive peptides, but also prominent neurotransmitters such as serotonin (in fact 80% of the body's Serotonin is produced or stored in the gut), account for the three basic mechanisms via which the gut interfaces with our external environment and exchanges information content with the rest of the body, including the brain. This threefold signal exchange system of the gut is called the enteric nervous system, and it is considered the third branch of our autonomic nervous system.

From an evolutionary perspective it has been noted that even evolutionary distant animals, such as spineless helminthes (parasitic worms like this friendly fellow) possess nervous systems very similar to our enteric nervous system; which (in combination with other observations) suggests - as noted in a recent review by UCLA researcher Emeran Mayer for the journal Nature - that

"the ganglia that form the primitive brains of helminthes and eventually the brains of higher mammals, were derived from the more primitive but homologous enteric nervous circuit. Thus, neural circuitries and transmitter systems that have evolved to assure optimal responses to the challenges presented in our internal environment may have been incorporated into the [central nervous system] during evolution.".

The enteric nervous system, so Mayer concludes further,

"can be viewed as a peripheral extension of the limbic system into the gut, where it is exposed closely to our complex internal environment.

The central and enteric nervous systems are closely related in this evolutionary sense. Moreover, strong innervation between the enteric and central system makes the academic distinction between the two appear almost artificial. The distinction is justified, however, not at last on the grounds that the systems can indeed operate somewhat autonomously.

This autonomy, nonetheless, must not be mistaken for the ability to act in isolation: It remains that both systems have so much overlap in functional pathways and the transmitter molecules they utilize that whatever happens in the central nervous system - and now I am especially thinking of the brain - will influence the nervous system that is seated in the gut. What happens in the gut, also will influence communication of neurons inside the brain; and by extension will have an impact on behavior. It is this realization that central and enteric nervous systems necessarily communicate in a bi-directional manner, which gives reason to medical researchers studying e.g. depressive symptoms, Parkinson's, or anxiety to turn to their patient's gut's, and why investigations of ulcers and constipation can justifiably focus on aspects of brain functioning.

For the last 15 years, scientific studies that focused on the role of brain-gut communications for specific physiological and psychiatric disorders have increasingly gained attention (a notable contribution is the 1998 book The Second Brain by Columbia University Anatomist Michael Gershon), and citing again Emeran Mayer, it can be said that

"tremendous progress has been made in our understanding of the bi-directional crosstalk between the brain and the digestive system This includes the remarkable success in mapping the functional neuroanatomy of the enteric nervous system, in out understanding of how the brain modulates these [enteric nervous system's] circuits and gut functions, and in unraveling the complexity of gut to brain signaling through multiple parallel but interacting communication challenges".

These terrific successes aside, the most striking thing to me, however, remains the assessment that

"many aspects of gut to brain signaling [...], in particular the role of this signaling in emotional and cognitive function, remain speculative at this point."

Indeed there is - as I mentioned at the beginning of this post - no shortage in yet-to-be-answered, but utterly fascinating questions surrounding this topic:

For example who would not want to investigate the role of gut-brain signaling in brain development during early life and it's influence in adulthood. More concretely Mayer formulates this question as 

"does gut to brain signalling early in life influence the development of adult ingestive behaviour, visceral pain sensitivity, mood and affect, interoceptive memory and intuitive decision making?"

Add to this - and related queries - questions about the role that the gut's fleet of microorganisms play for all of these processes and you are looking at an electrifying frontier of highly interdisciplinary scientific research.

As part of my academic background then, I am naturally inclined to wonder what kind of contribution economists might make in this type of research, which certainly appears to have strong implications for decision making and many other things economists are traditionally concerned with.

Possibly surprising to many people (certainly to non-economists), I believe that economics indeed has a lot to offer here (which, admittedly, is a biased position I endorse more generally). I believe this mostly because of two things that are central to the investigation of brain-gut commincation as it relates to behavior: These two things are the bidirectional nature of brain-gut communication and the central theme of homeostasis for the biology of organisms:

Regarding homeostasis - the dynamic equilibrium tendencies of organisms to maintain a stable internal millieu against changes in the outside environment - it is enough to note, that this central biological idea has a direct equivalent in the behavioral equilibrium that economists consider in virtually all of their research. To some extent, I am tempted to argue that economist's appreciation of dynamic equilibria is what sets the discipline apart from other social sciences, but this may be an extensive argument better saved for another blog post...

Regarding bidirectionality, it needs to be noted that truly bidirectional systems are not easily investigated with what might be called the "intuitive" scientific method - which is to systematically isolate and manipulate elements in a causal chain, observe how the system operates under these changes, and then piece back together how the system functions as a whole. Part of the difficulty that bidirectional systems present to the intuitive method (even when performed via sophisticated statistical analysis) arises because it is not really possible for us to meaningfully vary one variable while holding the other constant when the relationshp we're interested in is precisely how the two variables interact in concert.

As it turns out, however, economists are no strangers to such bidirectionlity (think about supply, demand and market prices being mutual causes of each other), and in fact, economics has brought forth an entire discipline (Econometrics) essentially devoted to identifying causality in systems which are - for some reason or another- not routinely accessible through "standard" statistical analysis and controlled experimentation. These methods have already found their way into other disciplines, and -so I believe - will continue to be helpful in many areas of interdisicplinary research. At least this is what my gut tells me. 

Main Reference: Mayer, E. "Gut-feelings: The emerging biology of gut-brain communication". Nature Reviews Neuroscience 12, 454-466 (August 2011) | doi: 10.1038/nrn3071

About the Authors

Kimberlee D’Ardenne, Ph.D.

Kimberlee D’Ardenne, Ph.D. is a neuroscientist by training, science writer by choice.

Rachael Grazioplene

Rachael Grazioplene is a graduate student in Psychology at the University of Minnesota. Her research is focused on individual differences and behavioral genetics.

Daniel Hawes

Daniel R. Hawes is a social psychologist stuck in an applied economist's body.

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