Team:Austin UTexas/HP/Gold Integrated

Gold Medal and Integrated Practices


Collaborative efforts with local professionals in science, medicine and social work allowed us to shape our project in an ethical and effective manner. We focused our human integration efforts on analyzing potential solutions to a problem that directly impacts the Austin, Texas community. According to a 2009 CDC report, roughly 12 percent of the Austin population was diagnosed with a mental affliction compared to a 10 percent prevalence nation wide (9). Because mental health is a significant issue in our region, we aimed to focus our project on the treatment of mental health diseases.


Confirming Our Project Potential

As noted in Human Practices, outreach to professors at the University of Texas was paramount in the development of our project. After reading an article suggesting that GABA may have anxiolytic effects from bacteria within the gut (2), we were unsure of the mechanism that this could occur. It was our understanding that GABA is unable to, or can only minimally, pass the blood-brain barrier (5). We reached out to Dr. Qingchun Tong, who has researched the influence of GABAergic systems on energy balance, for advice. He suggested that “..GABA may influence pancreas and gut function, which then in turn affects brain function through changes in hormones or other factors.” Essentially, he described the gut-brain axis. The gut-brain axis is a novel concept that describes the ability of our enteric nervous systems to communicate with our central nervous systems through neural and hormonal pathways (6). With confirmation that GABA might have significant effects on the central nervous system via the gut-brain axis, it became our molecule of interest.

Gut-brain_axis.png

Because GABA is inherently produced in small amounts by various bifidobacteria and lactobacilli within the human gut (7), it seemed logical to enhance the GABA production of one of these species so our modified bacteria could theoretically proliferate in the gut. At this point, we chose to manipulate Lactobacillus plantarum. This species is present in the human gut, produces GABA in a significant capacity and it is relatively well characterized in comparison to other lactobacillus strains (7)(8). Using Lactobacillus plantarum, we aimed to form a probiotic with an ability to produce therapeutic levels of GABA. This product could be packaged into a pill and used as medication or as a supplemental treatment for anxiety. Because the bacteria would have the ability to propagate in the gut, this probiotic could continue to produce therapeutic levels of GABA and have more long-lasting effects than a GABA supplement.


How to Improve the Current Medical Marketplace

In addition to anxiolytic effects, there are proposed antihypertensive effects of GABA (3). We discussed this idea with Austin Heart in order to learn how a product like this could fit into the current marketplace of hypertensive medication. Austin Heart, a local cardiology practice, was very helpful and supportive of the project. They explained that often times barbiturates have many negative side effects, such as inhibiting gut motility. GABA regulates gut motility (2), so this issue would be rectified with our proposed medication. However, the best advice they offered was to alter our delivery method. Dr. Roger Gammons said, “There is a lot of research into different types of drug delivery... There are situations where one drug may inhibit the absorption of another one because they may compete for the same pathway.. The treatment used is very specific to the patient. There are a lot of pills out there, but often times, that isn’t the best method.” We are working with bacteria, so it our simple solution was to alter our original probiotic pill into a fermentable food product that may be more beneficial for some patients.

Austin_Heart.png

Drug Delivery and Dosage

The fermentable food product went over well with Micki Marquardt from Helping Hand's Home for Children. She felt that a fermentable food such as yogurt, or dark chocolate would be a great method of drug delivery for children. This would prevent children from associating pills with positive benefits. However, she was concerned about the cells proliferation in the gut due to the higher chance of an overdose. In response we proposed to incorporate a regulation system using an agr quorum sensing mechanism from Staphylococcus aureus. The bacteria would respond to the environment and limit glutamate decarboxylase production after GABA was present in the desired levels. This addition to the project is not yet developed, but remains a future goal that we intend to work on after the iGEM competition.


References

  1. Violence Prevention. (2016, April 05). Retrieved June 29, 2017, from https://www.cdc.gov/violenceprevention/childmaltreatment/consequences.html
  2. Hyland, N. P., & Cryan, J. F. (2010). A Gut Feeling about GABA: Focus on GABA Receptors. Frontiers in Pharmacology, 01. doi:10.3389/fphar.2010.00124
  3. Shimada, M., Hasegawa, T., Nishimura, C., Kan, H., Kanno, T., Nakamura, T., & Matsubayashi, T. (2009, June). Antihypertensive effect of gamma-aminobutyric acid (GABA)-rich Chlorella on high-normal blood pressure and borderline hypertension in placebo-controlled double blind study. Retrieved June 02, 2017, from https://www.ncbi.nlm.nih.gov/pubmed/19811362
  4. Fichna, J., & Storr, M. A. (2012). Brain-Gut Interactions in IBS. Frontiers in Pharmacology, 3. doi:10.3389/fphar.2012.00127
  5. Gammons, R. (2017, June 21). Cardiologist Perspective [Telephone interview].
  6. Eisen, J. S. (2013). Faculty of 1000 evaluation for Gut-brain axis: how the microbiome influences anxiety and depression. F1000 - Post-publication peer review of the biomedical literature. doi:10.3410/f.718013229.793477291
  7. Yunes, R., Poluektova, E., Dyachkova, M., Klimina, K., Kovtun, A., Averina, O. Danilenko, V. (2016). GABA production and structure of gadB / gadC genes in Lactobacillus and Bifidobacterium strains from human microbiota. Anaerobe, 42, 197-204. doi:10.1016/j.anaerobe.2016.10.011
  8. Nguyen, T., Kang, J., & Lee, M. (2007). Characterization of Lactobacillus plantarum PH04, a potential probiotic bacterium with cholesterol-lowering effects. International Journal of Food Microbiology, 113(3), 358-361. doi:10.1016/j.ijfoodmicro.2006.08.015
  9. Psychological Distress. (2013, October 04). Retrieved September 08, 2017, from https://www.cdc.gov/mentalhealth/data_stats/nspd.html