The Gut-Brain Axis

These nerves [to the bowels] are but small, because the parts serving for nutrition, needed none but little nerves, for the performance of the third duty of the nerves, which is in the discerning and knowing of what is troublesome to them - Ambroise Paré, circa 1579

Although phenomena supporting the gut-brain connection have long been part of our history and culture, we are on the frontier in understanding HOW they are connected now with terms such as the Gut-Brain Axis. Yes, medical journals now exist devoted to the study of neuro-gastroenterology, and the term Melancholic Microbes has no doubt been crafted as the title of an academic article in said journals. 

In fact, the stomach contains more neurotransmitter receptors than the brain, and for good reason. At our very basest of needs as an organism is to consume food for energyin our case, sugars and fats. In times of food scarcity (all of history until ca. 1950), a key survival adaptation developed--a feeling of reward and bliss after eating, caused by a stream of dopamine in our brains. The punishment is harsh too: the clinical literature (and Snickers bar commercials) has well established that hunger causes anxiety and psychosis, among many other cognitive dysfunctions. Food addiction, loosely interpreted, could potentially be affecting millions of overeaters among us, and has been considered by some to be worthy of inclusion in the DSM-V as a defined disease.

The gut is also physically connected to the hypothalamus in the brain, directing the major endocrine (hormone) centers such as the pituitary, adrenal, and thyroid glands. Known as the HPA and HPT axes, these connections, based on our health, diet and genetic status, dictate energy metabolism as well as mental and emotional function through hormonal signaling mechanisms. Ingredients that support the HPA and HPT axes may address hunger signaling, in addition to the downstream effects (feelings of hunger and contentedness) that ultimately influence our daily eating behaviors.

As an example of the Gut-Brain Axis as a platform for development of therapeutics, in 2012 FDA approved lorcaserin (Belviq), the first obesity drug approved in several years whose mechanism of action is neurotransmitter activity. Lorcaserin, like serotonin, curbs appetite in the hypothalamus through serotonin receptor 2c agonist activity. However, this small molecule compound not present in the natural world has been the subject of recent safety concerns. Fortunately, herbs such as ginseng and bacopa have also demonstrated activity at serotonin receptors. Saponin glycosides from Bacopa monnieri (subset of the so-called bacosides) have been isolated using HPLC, and shown to bind to human serotonin receptor 5HT1a with agonist activity. Likewise, improvements in measures of mood and anxiety have been shown in multiple clinical trials on these herbs.

Diet can cause changes in the brain, and the gut can be a major source of systemic inflammation (due to gut microflora imbalance) that can elevate basal levels of neuroinflammation. In fact, this connection has been named as a primary target for potential therapeutics in systemic and neuroinflammatory disorders like autism and fibromyalgia. There are some anti-inflammatory compounds that also possess neurotransmitter activity, such as curcumin, blueberry, and green tea. The pleiotropic effects of these powerful dietary compounds are keys to their potential value in supporting health in a broad range of areas affecting both the gut and brain. 

Glutamate, the essential amino acid that tastes meaty and delicious in the form of MSG, also plays a critical role in neuroinflammatory signaling and the aging brain. We are actively looking for natural compounds that can help to support the emotional reward centers stimulated by glutamate, sugar, and fat, which can help to manage the amount of these double-edged ingredients that are generally over-consumed.

Holism and reductionist science have long occupied opposite ends of the spectrum of reality. But todays medical and scientific discoveries speak more to their power when used together, helping us understand how connected each of our bodys systems really are.