It seems like no other phenomenon has so far reaching
consequences as stress. Its past could be stretched to millions of years,
during which it helped our ancestors to trigger most basic reaction of fight or
flight, essential for their survival.
Straight from the evolutionary past comes the gut wrenching
feeling which slowly dawns when presenting a talk in front of large audience. No
matter how confident one might be, there is no escape from these proverbial
butterflies in stomach. Simple act of presentation or impending examination leads
to huge increase in appetite of some but not the others.
Under these normal observations comes a deep rooted scientific question.
How does my gut interact with my brain and vice versa?
Some recent scientific observations reveal that our gut contains as much as 500 million neurons[1]. In comparison, spinal cord is distant third with its 100 million neurons. Nervous system of gut is called Enteric Nervous System (ENS) and it underlines all gastrointestinal activities. Huge numbers of neurons point out the extensive area where ENS function. Digestion is so intricate that nature has given “alimentary brain” separately to handle this task. It evolved around 500 million years ago, long before thinking brains developed. We share stark similarity in our gut brain with our fellow vertebrates. Our main brain might have developed greatly because all the digestion related tasks were handled by the ENS, Some even speculate its origin from ENS.
ENS extends its nervous territorial control from esophagus to anus. Its complicated tasks include timely contraction & relaxation of smooth muscles which moves food items through the alimentary canal. Time and space holds central importance in ENS functionality. As biochemical environment differs in each compartment from stomach to large intestine, correct timing and ratio of enzymes delivered, its pH has to be maintained by ENS. It has to give signals precisely on time to specific cells to secrete its components.
This coherent and concerted activity of so many neurons requires more than 40 neurotransmitters, same as that of brain. ENS is laced with these tiny communicating molecules. About 90% of body serotonin levels & 50 % Dopamine levels reside in ENS.
Importance of ENS could be gauged with diseases that arise due to its under-development –
Esophageal Achalasia (no relaxation of esophagus) – Improper functioning of esophageal neurons leads to condition in which muscle fibers fail to relax leading to difficulty in swallowing.
Gastroparesis (partial paralysis of stomach) – Delayed gastric emptying or When food stays in stomach for abnormally long time leading to nausea & palpation. This occurs when vagus nerve controlling gastric functioning is damaged.
Hirschsprung's disease– due to malfunctioning/absence of neurons in large intestine leading to vomiting and bloody diarrhea.
Chagas Disease – 10% of Patients suffering from this disease develop megacolon (enlargement of large intestine) due to loss of nearly 80% neurons there. This sometimes lead to fecaloma (faecal tumours) as bowels form immovable hard mass inside the colon, it requires surgery to remove it.
Intestinal Pseudoobstruction – When intestine fails to push food it leads to vomiting and bloody diarrhea. This condition can begin at any age and is idiopathic (unknown, spontaneous origin) .
Proper functioning of ENS is so central to our well-being that slight disturbances can wreak havoc on our body homeostasis. It especially comes under light when there are pathogens in our food. It is emphasized that although our body may initially swallow contaminated food but it can’t escape the ‘eyes’ of ENS. Our body quickly responds by going into damage control mode as it induces vomiting and diarrhea to swiftly expel the pathogens. However, the role of other important limb i.e gut immunity cannot be underestimated. Immune cells release histamines affecting neurons of ENS to initiate diarrhea/vomiting. This system is sometimes hijacked by organisms like Vibrio Cholera and Rotavirus. They release toxins which have been shown to directly effect secretory neurons of the gut.
Recent observations shed some light on whether gut has any influence on mood or vice versa?
In a study, Vagus nerve stimulation led to treatment of chronic depression (2). Of all the signals the Vagus nerve or pneumogastric nerve carry 90% of the signals from gut to brain [3]. This is direct link between ENS and Brain. Some studies are trying to find out agents which might pass upward from ENS to brain and cause diseases like Parkinson.
Also, Higher doses of fatty acid led to lower sadness in a group of volunteers versus participants who were given saline (4). Ghrelin (hunger hormone secreted by specialized cells) production is increased during hunger but it also reduces anxiety and depression. These traits were helpful in our ancient past as it kept our ancestors calm when venturing out for food.
Patients with Parkinson disease loose dopamine producing cells in their brain. Lewy bodies, protein aggregates slowly degenerates the neurons. But strangely, same protein clumps are also found in dopamine producing neurons in gut. Similarly, Alzheimer disease showcases similar pathology in gut too. There is also a positive correlation between Autism and gastrointestinal problem. Similarly, Gut infection or stress early in childhood is risk factor for developing Irritable Bowel Syndrome (IBS) later in adulthood.
Above observations proves that we have just started to scratch the surface. More questions arise but the answers are already burdened by multitude of questions.
How are both ‘brains’ connected , as they malfunction simultaneously? How does it ‘spread’?
Which ‘brain’ begins to degenerate first?
In another pioneering experiment, mice exposed to mild stomach irritant remained depressed even long after physical damage was gone [5]. This didn’t happen in negative control in which there was skin irritation. Only mice with digestive irritant showed depression but not the other.
One thing that goes simultaneously is the complexity of the whole operations. Neurons, Immune cells, Muscle cells, secretory cells and countless other types of cells with their concerted actions help to maintain homeostasis and sustain life. Many more factors are still not known. With more than 100 trillion friendly microbes (ten times number of cells in our body) sitting in our gut, there might be active interaction going on between our second brain and this microbiome. It just needs an eavesdropper to just observe and report it. Many more breakthroughs awaits in this wonderful field of neurogastroenterology.
Reference:
1. Furness, John Barton. The enteric nervous system. John Wiley & Sons, 2008.
2.
Nahas,
Ziad, et al. "Two-year outcome of vagus nerve stimulation (VNS) for
treatment of major depressive episodes." The Journal of clinical
psychiatry 66.9 (2005): 1097-1104.
3.
Powley,
Terry L., and Robert J. Phillips. "I. Morphology and topography of vagal
afferents innervating the GI tract." American Journal of
Physiology-Gastrointestinal and Liver Physiology 283.6 (2002):
G1217-G1225.
4.
Van
Oudenhove, Lukas, et al. "Fatty acid–induced gut-brain signaling
attenuates neural and behavioral effects of sad emotion in
humans." The Journal of clinical investigation 121.8 (2011):
3094.
5.
Al–Chaer,
Elie D., Motohiro Kawasaki, and Pankaj J. Pasricha. "A new model of
chronic visceral hypersensitivity in adult rats induced by colon irritation
during postnatal development." Gastroenterology 119.5 (2000):
1276-1285.
More to explore:
1. Young, Emma. "Alimentary thinking." New Scientist 216.2895 (2012)
2.
Hadhazy,
Adam. "Think twice: How the gut’s “second brain” influences mood and
well-being." Scientific American 12 (2010).
3.
Furness,
John B. "The enteric nervous system and neurogastroenterology."
Nature Reviews Gastroenterology and Hepatology 9.5 (2012): 286-294.
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