This article was written with reference to the article contributed to the New York Times on January 28, 2019 (https://nyti.ms/2CV37me) and permission to quote parts of the article has also been obtained.

1. Master of Your Mind

There is a saying to be the master of your mind. It means to maintain calm and not be influenced, even when something bad happens. Whether it’s when your scalp tingles from consecutive deaths in a game, or when unexpected rain on a day you planned to go out makes you depressed. Whether it’s when soup splashes onto your white shirt that you wore with a great deal of effort, and you feel bad - it’s about taking a deep breath and calming your mood.

However, there is one premise to this maxim. It is the assumption that our mind is up to us. But this is not as simple as it sounds. As psychology and neuroscience have advanced, we have come to understand that the mind is not just our own will, but the result of complicated neural activities. Depression, for instance, doesn’t get better just by deciding to ‘be happy’.

Here, I want to add one more reason why our mind doesn’t go as we wish. It’s the food we eat every day.

Eating delicious food makes you feel good. Even just looking at it too. Isn’t it such an obvious and happy story?

2. What Are Gut Bacteria?

It’s not simply saying that eating delicious food makes you feel good. Of course, if you fail to select a good lunch menu, you’ll feel down all day until you refresh yourself with a delicious dinner. But there is another fundamental reason that the food we eat every day affects our mind. It is the gut bacteria that grow by eating the food we intake.

Gut bacteria, as the name implies, are bacteria residing in our intestines. Even if you are hearing the term ‘gut bacteria’ for the first time, you might have heard of E. coli. It’s named E. coli not because it’s the boss of all bacteria, but because it resides in the colon. Anyway, there are about 1,000 types and approximately 10 trillion bacteria like E. coli existing in our intestines. [1] The reason why products like probiotics are sold for health is based on this fact.

It’s no longer surprising that these microorganisms affect our gut health. In fact, gut microorganisms are considered a cause of many gastrointestinal diseases, and fecal microbiota transplantation (FMT), which replaces gut microorganisms, is being anticipated as a potential treatment for gut diseases. There is still debate about whether it is practically effective, though.

Microorganisms that can cause gastrointestinal diseases

For example, Clostridium difficile is famous for causing pseudomembranous colitis, a type of diarrhea, when the balance of gut microorganisms is disturbed by antibiotics usage. FMT is being noted as a potential treatment for this disease. [2] It’s also known to be effective in improving inflammatory bowel disease, obesity, and metabolic disorders. [3][4]

The reason FMT shows such effects on gastrointestinal diseases is known to be because it influences the activation of immune functions in our intestines. Exposure to antibiotics during childhood can disrupt the balance of gut microorganisms, increasing the likelihood of inflammatory bowel disease later. On the other hand, people who suffered from gastrointestinal or respiratory diseases during childhood have a lower probability of suffering from inflammatory bowel disease as their gut immunity is activated.

But what if these gut microorganisms also affect our brain? Intuitively, it might be hard to understand. What could be the connection between what’s happening inside our gut and brain activities? For example, the words gut bacteria and Alzheimer’s might seem unrelated at first glance. This was also the reaction of those listening to Dr. John Cryan’s claims at the Alzheimer’s Association International Conference in 2014. [5]

The connection between brain activity and the digestive system, including gut microorganisms, is also described as the Gut-brain axis.

3. Hotline Between Brain and Gut

Dr. John Cryan, a researcher in microbiology at University College Cork in Ireland, argued at the conference that the microorganisms symbiotic in our bodies affect our thoughts and behaviors and could influence the progression of Alzheimer’s. This was not well accepted at the time. It’s logical to say that microorganisms influence gut health since the gut is where they reside, but our brain is a crucial organ protected by the blood-brain barrier (BBB). It was initially unacceptable to think that gut microorganisms could influence the brain through the barrier that allows only certain types of molecules to pass through.

Subsequent evidence, however, supported the relationship between our brain and gut bacteria. Dr. Sangram Sisodia at the University of Chicago found some evidence to support Dr. Cryan’s thoughts. Alzheimer’s progresses as a type of protein debris called beta-amyloid plaque accumulates in the brain. In 2016, Dr. Sisodia reported that administering antibiotics to genetically modified mice prone to Alzheimer’s reduced gut microorganisms, resulting in less beta-amyloid plaque. This suggested that gut microorganisms might be involved in the progression of Alzheimer’s.

Research suggesting the connection between gut bacteria and brain activity has continued. For example, mice without gut bacteria were reported to feel loneliness more easily compared to other mice, a result caused by abnormal protein production in the amygdala of those mice. [6] Moreover, in 2016, it was reported that the gut bacterial patterns of children with autism spectrum disorder differ from those of normal children. [7]

However, these studies were insufficient to determine causal relationships between neurological disorders and gut bacteria. It was unclear whether having the disease changes gut bacterial composition or different gut bacterial compositions cause the disease.

To clarify this, some researchers conducted studies using fecal transplantation. For example, feces from genetically modified mice prone to obesity due to increased appetite were transplanted into germ-free mice’s guts, and the recipient mice also showed increased hunger. [8] There were also studies where feces from depressed individuals were transplanted into mice, and those mice showed symptoms of depression. Recently, fecal transplantation was even reported to potentially improve depression in humans. [9]

Does it mean that cultivating good gut bacteria through a healthy diet is involved in brain health?

4. There Is Still a Long Way to Go

Looking at the above studies, one can envision a future where various diseases are treated by enhancing beneficial gut bacteria and eliminating harmful ones. However, to achieve this, we must overcome a major limitation in gut bacteria research, which is the difficulty in identifying exactly which microorganisms alter our behavior. The aforementioned studies inform us that gut bacteria of individuals with depression affect their behavior, but exactly which microorganism causes the disease is still unknown. In fecal transplantation studies, it’s challenging to determine the exact effect of specific microorganisms since hundreds of species are transplanted at once.

Additionally, how to safely use gut microorganisms in treatment requires further consideration. On the 13th, the FDA warned about the risk of multi-drug-resistant bacteria, so-called “superbugs,” spreading through fecal transplantation and causing patient death. Fecal transplantation is used experimentally to treat gastrointestinal infections caused by C. Difficile. In the reported case, recipients with immunosuppression were infected and killed by E. coli producing specific enzymes from the donor’s feces. [10] The FDA proposed strengthening the donor screening process to prevent multidrug-resistant bacteria from being selected as donors. Before using gut microorganisms for medical purposes, determining how to safely control and utilize bacteria that might cause unexpected infections is essential.

However, there are signs that the difficulty in identifying the benefits provided by bacteria in our body will be resolved. It is because more reports are revealing the specific effects of certain gut bacteria on brain activities. A research team led by Costa-Mattioli at Baylor College of Medicine reported that transplanting specific microorganisms could improve the antisocial behavior of mice showing symptoms of autism. It was because the social behavior of antisocial mice improved after injecting Lactobacillus reuteri, commonly used in probiotics medication.

L. reuteri secretes substances that stimulate the vagus nerve, one of our brain nerves, and this stimulation activates oxytocin secretion, which promotes social activities. [11] Increasingly, studies suggesting the relationship between gut microorganisms and neurological symptoms are being reported. Recent studies even suggest that the presence of particular gut microorganisms might cause locomotor ataxia, a symptom of Parkinson’s disease. [12] Besides the neurological symptoms caused by gut microorganisms, active research continues on their effects on our bodies, for example, a Harvard Medical School team linking Ruminococcus gnavus to irritable bowel syndrome represented by Crohn’s disease. [13]

Is it possible that being inoculated with ‘popular bacteria’ like L. reuteri makes one more sociable?

5. Conclusion

There’s a saying heard frequently when you go to the gym to get in shape: exercise is half about diet. Indeed, our diet becomes a part of who we are. It means consuming high-quality protein and reducing fats and carbohydrates to build muscle, and taking a healthy diet for a healthy body. This saying is about to have a new meaning. Maintaining a healthy diet for healthy gut bacteria leading to a healthy brain is becoming the norm. Food affects our gut bacteria, and these gut bacteria, in turn, influence our brain activity.

The saying “a healthy mind in a healthy body” might become outdated. In the future, we may start saying “healthy gut bacteria create a healthy mind.” Gut microorganisms are not the sole cause of neurological diseases, and consuming probiotics is not a panacea. However, as the correlation between our gut inhabitants and our brain activities becomes thoroughly elucidated in the future, isn’t there a chance that a simple diet adjustment could enable people to live a mentally healthy life someday? Hoping that such a day will come soon, I conclude this article.

References:

[1] https://www.gutmicrobiotaforhealth.com/en/about-gut-microbiota-info/

[2] Hamilton MJ, Weingarden AR, Sadowsky MJ, Khoruts A.Standardized frozen preparation for transplantation of fecal microbiota for recurrent Clostridium difficile infection. Am J Gastroenterol 2012; 107:761-7; PMID:22290405;

[3] Gupta, Shaan et al. “Fecal microbiota transplantation: in perspective”Therapeutic advances in gastroenterology vol. 9,2 (2016): 229-39.

[4] Weingarden, Alexa R and Byron P Vaughn. “Intestinal microbiota, fecal microbiota transplantation, and inflammatory bowel disease” Gut microbes vol. 8,3 (2017): 238-252.

[5]https://www.nytimes.com/2019/01/28/health/microbiome-brain-behavior-dementia.html

[6] Stilling, R., Moloney, G., Ryan, F., Hoban, A., Bastiaanssen, T., Shanahan, F., Clarke, G., Claesson, M., Dinan, T. and Cryan, J. (2018). Social interaction-induced activation of RNA splicing in the amygdala of microbiome-deficient mice. eLife, 7.

[7] Vuong, Helen E and Elaine Y Hsiao. “Emerging Roles for the Gut Microbiome in Autism Spectrum Disorder” Biological psychiatry vol. 81,5 (2016): 411-423.

[8] Vijay-Kumar, Matam et al. “Metabolic syndrome and altered gut microbiota in mice lacking Toll-like receptor 5” Science (New York, N.Y.) vol. 328,5975 (2010): 228-31.

[9] Kurokawa, Shunya, et al. “The Effect of Fecal Microbiota Transplantation on Psychiatric Symptoms among Patients with Irritable Bowel Syndrome, Functional Diarrhea and Functional Constipation: An Open-Label Observational Study.” Journal of Affective Disorders, vol. 235, 2018, pp. 506–512., doi:10.1016/j.jad.2018.04.038.

[10] https://www.fda.gov/vaccines-blood-biologics/safety-availability-biologics/important-safety-alert-regarding-use-fecal-microbiota-transplantation-and-risk-serious-adverse

[11] Sgritta, Martina, et al. “Mechanisms Underlying Microbial-Mediated Changes in Social Behavior in Mouse Models of Autism Spectrum Disorder.” Neuron, vol. 101, no. 2, 2019, doi:10.1016/j.neuron.2018.11.018.

[12] Sampson, Timothy R., et al. “Gut Microbiota Regulate Motor Deficits and Neuroinflammation in a Model of Parkinson’s Disease.” Cell, vol. 167, no. 6, 2016, doi:10.1016/j.cell.2016.11.018.

[13] https://hms.harvard.edu/news/microbiome-malefactor?utm_source=twitter&utm_medium=social&utm_campaign=hms-twitter-general