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Neuroscience

The Intimate Gut-Brain Connection

Introduction:

In the last decade, research in the field of the gut-brain connection has tremendously increased, providing advanced neurobiological insights to the treatment of mental illnesses like clinical depression and anxiety. When scientists worldwide recognized the medical implications of the bidirectional gut-brain axis, the biochemical signaling between the cognitive centres of the brain and the intestinal tract, several psychological and neurodegenerative diseases such as Alzheimer’s and Parkinson’s were re-evaluated to a large extent. Moreover, new therapeutic approaches for type 2 diabetes, obesity, and others were deduced. Although this field of research is still in its infancy, through the exploration of various studies conducted, this article will explain how the gut-brain connection influences intuitive decision-making, emotional states, and the mere functionality of the human brain. 

What is the ENS?

The brain is often mistaken as the most diverse organ when the gut clearly supersedes it by possessing 5 times the number of neurons present in the brain. Surprisingly, the gut has a brain of its own which medical practitioners call the Enteric Nervous System (ENS). Comprising 2 fine layers of 100 million neurons and more, the ENS can be traced through the gastrointestinal tract, beginning in the esophagus and ending in the rectum. Fundamentally, the ENS orchestrates the process of digestion, from the mastication of food in the mouth to the elimination of waste. Throughout this process, the ENS has been found to communicate back and forth with the brain. One example of the intricate gut-brain bidirectional system is the involuntary flight or fight response. The Central Nervous System is triggered and the Enteric Nervous System responds by completely halting digestion or reducing its speed so that energy spent on it can be redirected to muscles elsewhere to act upon the danger which initiated the fight or flight response. 

History of Research

Historically, advances in findings of the ENS were minimal; scientific trade was limited because it was seen as a collective endeavor of only a few communities. Furthermore, the economic model for bioengineering didn’t provide enough financial incentive to motivate scientists to carry out research back then. However, our triumphantly digitized contemporaneity has enabled us to improve our understanding through sophisticated scientific apparatus. Gut microbiomes are unique to each individual like DNA, and it appears to colonize at birth itself. Aiding in digestion, metabolizing medications and so much more, our gut microbiomes hold enormous significance to our body. Until 2004, it was highly doubted that the gut microbiota could affect mental health. However, Nobuyuki Sudo disproved this theory when he declared the observations of the study he conducted at Kyushu University, Japan. He confirmed that the mice which were so-called germ-free exhibited a fiercer reaction when exposed to stressors compared with the normal mice. Germ-free mice are organisms grown in a controlled and quarantined environment so that they have no microorganism exposure at all This experiment garnered international attention after which researchers began exploring this department in depth. 

The Vagus Nerve and the Forced-Swimming Experiment:

Prior to this, the concept of alteration of behavioral appearances of mice by making changes to their gut was unprecedented. In the year 2010, the European Union authorized the simulation of the vagus nerve in medical treatment for patients suffering from depressive disorders. The vagus nerve is distinguished for the extensive range of organs it connects to the medulla oblongata, a grape-sized tissue at the base of the brain. Being complex and long, it serves as a platform of communication between the brain and the gut. Essentially, the modulation of this nerve affects the psychological and physiological states and alters any bodily processes dependent on information exchange between the two. A pioneer in this field, Jay Pasricha, M.D., director of the Johns Hopkins Centre for Neurogastroenterology, whose research has been recognized globally, explains that these findings better demonstrate why patients suffering from irritable bowel syndrome, constipation, and diarrhea have been found to develop depression on a more-than-normal scale. This emphasizes how important this is because up to 30 to 40 percent of us go through irritable bowels at least once in a lifetime. Following the approval of modulation of the vagus nerve, an innovative experiment was engineered by a team commanded by an Irish scientist, John Cyran, whose forced-swimming test  revolutionized medicine permanently.

The forced-swimming study was primarily designed to test out antidepressants on mice. Mice are placed in identical containers of deep water, coercing them to try to remain afloat by swimming. The principle of this experiment epitomizes the significance of life and how determined the mice were to strive towards something abstract and intangible like happiness. Mice with depressive tendencies gave up quickly; in fact, they did not even make an effort and apathetically anticipated death. This displays that inhibitory signals were distributed around more productively than motivational signals resulting in stronger reactions to stress in their brains. Antidepressants were then tested on these mice and, if they made an effort to swim or outdid their recorded time compared to their previous attempt, it indicates that the drug has worked. What was a simple experiment was redesigned by Cyran by giving half of these mice Lactobacillus rhamnosus JB-1, a strain of bacteria typically found in yogurt, resulting in the mice fed with the bacteria strain exhibited improved behavioral, physiological, and cognitive functions proving that the wellbeing of the gut influences the functionality of the brain. Remarkably, the mice fed with this strain were more driven and to swim longer. Additionally, fewer stress hormones were detected when compared to the previous blood samples, and this set of mice achieved better than the other set in both learning and memory tests.

Stimulation of the Brain to Establish a Connection Between the Gut and the Brain

Following Cyran’s research, in 2013, the first study on the effect of gut health on human brains was published. The scientists who pioneered this research at UCLA were astonished by the results. What they had expected were no visible changes in the brain. However, after 4 weeks of observations with 3 groups of women -one group being fed with a culture of probiotics, another with a placebo (a product that looked and tasted like yogurt, in this case), and another with nothing at all – the results were extraordinary. 

All the 3 groups were scanned in 2 different states, one resting and when performing an emotion-recognition test. This test measures the ability of the subjects to identify six basic emotions by recognizing facial expressions when viewing a picture. This test was picked due to the exposure of visual stimuli which will help in determining the differences in the cognitive area of the brain. The scientists reviewed the Functional Magnetic Resonance Imaging (fMRI) scans before and after the experiment and then established that some areas of the subject’s brains were undoubtedly modified, particularly in the areas responsible for managing emotions and physiological  states. 

Conclusion:

After 30 years of correlating intestinal health with the brain, it can be unequivocally said that the gut microbiome does influence certain parts of the brain controlling behavior and brain function. What followed was using this information to alter treatments by regulating the gut microbiota of an individual. The over-intake of high energy foods combined with inadequate exercise is blamed to be the primary cause of obesity. Since the 1980s, 13% of adults started battling obesity which was a very concerning case. 

This led pharmaceutical companies to spend billions on manufacturing “diet pills” and formulating drugs in vain. Medical representatives globally speculated an escalation of cases of cardiovascular diseases, osteoarthritis, sleep apnoea, immune weakening, endocrine complications, and low degree inflammation, but the most distressing one was type 2 diabetes. 

When the gut microbiota was explored in obese patients, it was found that there were excessive microorganisms that obtained more energy from the diet. However, the increase in fat mass is not only due to a more efficient harvest of energy, but also the microbiota participating in changes in systemic inflammation, bowel permeability, insulin resistance, and other protein synthesis processes like lipogenesis. Therapeutic approaches for obesity including the modulation of the gut microbiota include: the usage of prebiotics and probiotics, impressive antibiotic therapies, gut microbiome transplants, and other upcoming cures for mitigating metabolic disorders like pre-diabetes and resistance to insulin. This was very contributive to the diabetic community because even though insulin was discovered in the early 1920s, it was not procurable until a lot later. 

To conclude, this connection is revolutionizing medicine’s perspective of mental and psychological disorders, changing the course of prognosis for a multitude of illnesses and providing a ray of hope for finding cures for chronic diseases. 

Parineeta Karumanchi, Youth Medical Journal 2021

References:

Carabotti, M., Scirocco, A., Maselli, M. A., & Severi, C. (2015). The gut-brain axis: Interactions between enteric microbiota, central and enteric nervous systems. Annals of gastroenterology. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4367209/.