Team:Austin UTexas/HP/Gold Integrated

Gold Medal and Integrated Human 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.

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 communicate and do 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.

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. 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.

In addition to the 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.

References

    Violence Prevention. (2016, April 05). Retrieved June 29, 2017, from https://www.cdc.gov/violenceprevention/childmaltreatment/consequences.html
    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
    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
    Fichna, J., & Storr, M. A. (2012). Brain-Gut Interactions in IBS. Frontiers in Pharmacology, 3. doi:10.3389/fphar.2012.00127
    Gammons, R. (2017, June 21). Cardiologist Perspective [Telephone interview]. 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
    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
    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
    Psychological Distress. (2013, October 04). Retrieved Sptember 08, 2017, from https://www.cdc.gov/mentalhealth/data_stats/nspd.html