Yuka Masamura '21

Have you heard of folklores such as “Japanese ginger makes you forgetful” “drinking tea enhances oral hygiene,” or “Manuka honey is good for your health”? Is there really a direct cause and effect relationship between these foods and human health? I began to wonder about these different ideas while trying to find a way to prevent disease through lifestyle.

To explore this topic in depth, I met some scientists, most of whom were researching in the field of microbiome. I began to think of how the human microbiome and its balance affect our health after hearing a variety of stories. For instance, in one event that I attended during summer of 2019, I learned how the amount of lactic acid bacteria can positively affect the health of pregnant women and their infants, especially in regards to their success in delivering babies. While I received feedback from researchers and researched more about the correlation between health and the microbiome, I discovered the brain-gut axis, which has become the center of my research.

Brain-gut axis is “a bi-directional system of communication between the brain and the gastrointestinal tract, linking emotional and cognitive centres of the brain with peripheral control and function of the gut” (Jenkins et al.). Let me explain what that means with some studies that have shown how a change in gut microbiota influences the host’s mental condition.

In a study done at Karolinska Institutet in Sweden regarding the relationship between gut microbiota and behavior of mice, Dr. Heijtz’s team found that when the gut microbiota is absent, mice become aggressive and have unstable behavioral patterns. However, mice with normal gut microbiota and GF(germ-free) mice which received gut microbiota earlier in life had normal behavioral patterns (Heijtz et al.). The result demonstrates that the presence or absence of gut microbiota possibly affect the behavior of mice.

Studies on the relationship between gut microbiota and host’s mental health includes that of fecal transplant. Fecal transplant is a process in which the bacteria extracted from a healthy person’s feces is transplanted to another person to cure conditions like Clostridium difficile colitis. In one study, it has been reported that fecal microbiota transplant can cure mental illnesses such as chronic fatigue syndrome. 43 patients of this illness went through fecal microbiota transplant. After 15-20 years, 12 out of 43 patients reported that they fully recovered and 5 other patients also didn’t experience symptoms of chronic fatigue syndrome for a short period of time (Evrensel and Ceylan).

Based on this research, in addition to other studies, the brain-gut axis is believed to be the key to finding ways to improve mental health with a change in gut microbiota.

Our current world has sources of great stress, such as COVID-19 pandemic, natural disasters, and racial discrimination. My homeland, Japan, is said to have a high level of stress in its society as well. It is considered possible to improve mental health with a change of gut microbiota through the improvement of diet and fecal transplant. I hope to contribute this effort through my current research.

My research started with researching the topic I am working on and finding connections between information that I find. Once I had enough information to conduct data analysis, I became an intern at Cykinso, a startup that specializes in intestinal flora analysis, and used its data to conduct a data analysis. Through the data analysis, I would like to find “factor X”, the difference in gut microbiota between the healthy and the people who struggle with their mental health. This “factor X” could be the presence of, compositional balance of, or the variety of gut microbiota.

To start off, I prepared data samples using Jupyter Notebook, a software used for data analysis, and Jupyter, one of programming languages, for preparing and analyzing data from Cykinso. The data collected by Cykinso comes with survey responses. The survey included a test called CES-D (an abbreviation for The Center for Epidemiologic Studies Depression Scale), a self-evaluation system for depressive symptoms.

I then eliminated the samples that had no survey response regarding CES-D. I used the result of the survey to calculate the CES-D score of the samples remaining. As a result, I was left with 3,782 samples. Among those, I eliminated the samples that had major causes for the change in gut microbiota other than mental health. I will list the survey topics and the number of samples that were consistent with the topic as follows.

• has chronic illness (1281 samples)

• has Helicobacter Pylori treatment experience (508 samples)

• has been diagnosed with Colon cancer in the past (245 samples)

• has recently been diagnosed with bacterial enteritis (53 samples)

The number of samples I had left after eliminating the above was 2105. The graph below shows the distribution of CES-D score of those 2105 samples.

I separated these 2105 samples into 2 groups based on the CES-D score; Group A, a group with strong depressive symptoms, and the rest in Group B. Group A had 462 samples, and Group B had 1643 samples.

For reference, I also examined the breakdown of the sample for the following four sections of the survey that are likely to affect the changes in intestinal bacteria.

Medicine intake

Yes: 389

No: 1691

N/A: 25

Supplement intake for more than 4 days a week for a past month

Yes: 758

No: 1347

Frequency of diarrhea in the last 3 months

Always（more than 2/3）: 70

Yes（less than 2/3）: 718

No/Never: 1317

Constipation in the past 3 months

Yes: 383

No: 1722

These will be excluded from the analysis sample when necessary.

I plan to look for changes in intestinal bacteria between a group of people with a depressive tendency and a group of healthy people. The goal is to find strains that are more or less common in people with depressive tendencies, or to find structural differences. I would like to find out the characteristics of the flora of people with a depressive tendency, and to lead to treatments useful for health and changes in lifestyle.

Bibliography

Evrensel, Alper, and Mehmet Emin Ceylan. "Fecal Microbiota Transplantation and Its Usage in Neuropsychiatric Disorders." Clinical Psychopharmacology and Neuroscience, vol. 14, no. 3, 31 Aug. 2016, pp. 231-37, doi:10.9758/cpn.2016.14.3.231.

Heijtz, R. D., et al. "Normal Gut Microbiota Modulates Brain Development and Behavior." Proceedings of the National Academy of Sciences, vol. 108, no. 7, 31 Jan. 2011, pp. 3047-52, doi:10.1073/pnas.1010529108.

Jenkins, Trisha, et al. "Influence of Tryptophan and Serotonin on Mood and Cognition with a Possible Role of the Gut-Brain Axis." Nutrients, vol. 8, no. 1, 20 Jan. 2016, p. 56, doi:10.3390/nu8010056.

Moayyedi, Paul, et al. "Faecal Microbiota Transplantation for Clostridium Difficile ‐associated Diarrhoea: A Systematic Review of Randomised Controlled Trials." Medical Journal of Australia, vol. 207, no. 4, Aug. 2017, pp. 166-72, doi:10.5694/mja17.00295.