Team:KUAS Korea/HP/Gold Integrated

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Integrated Practices

Possible Practical Problems in Commercialization

The interview with Asia’s first stool bank, Gold biome influenced us in strain selection and factors to consider in the industrialization process. Our team met Suk Jin Kim of Suk Jin Kim laboratory institute and discussed the MSA, FMT(Fecal microbiota transplant) of the company and the product developing a process for our project. We tried to compensate our project by reflecting the feedback and make our design into a real product which can make people more convenient. Utilizing bacteria in the food/medicine industry needs to conform to exceeding regulations of KFDA, and the institute recommended us to select target strains among the 19 authorized bacteria. When we proposed our initial experiment plan that used Lactobacillus Casei, the director stated that the percentage of lactobacillus consisting human fetus is below 1% and would not be the most appropriate bacteria for fetus pigmentation. He recommended using Bacteroides or Prevotella, which are dominant species in human gut in order to produce enough amount of pigment for visualization. In addition, they told us that the number of micro bacteria permitted to be included in food products is below 10 million, so we should also consider a number of micro bacteria that is being taken in at a time. However, the researchers do agree to the fact that lactobacillus is the most commonly used bacteria in the food industry, and has the high possibility in application to various products.They advised that if we solved the problem of sufficient pigment production for visualization, it would be suitable for actual product making with Lactobacillus.

Also, when we discussed the product description of our project, we got practical feedbacks that focused on fulfilling the government requirements and safety issues. Korean media and the society are showing negative response towards genetically engineered products, and the strict government regulations do not easily allow GMOs until they pass the examination process of KFDA. These obstacles will make it hard for the release of the probiotics using synthetic biology. Apart from product release in the market, our consultation of product design process was mainly divided into delivering form and number of micro bacteria needed per intake. Our team previously thought of capsules that are only activated in intestines by pH condition. The director responded that capsule was a great idea to deliver as much lactobacillus to the intestine and fetus, but in that case, we should target specific conditions of the intestine that is not available in other organs. Furthermore, during the digestion process, the product will pass the stomach of the PH2 condition, which will not leave the bacteria alive until they make it to stomach. The capsule will be an efficient protection gadget for lactobacillus. Furthermore, the number of bacteria that should be loaded for one product also needs to follow government regulations. The CFU that is needed to be in one product is above 100 thousand and below 10 million bacteria. The probiotic product of Gold Biome includes 45 million bacteria due to the special government patent they registered. Regarding the small number of bacteria remaining in the fetus, we should put as many micro bacteria as possible in the capsule. Not all bacteria we intake survive, so the upper boundary for a number of bacteria may not be enough to show a dramatic change in fetus color. This is another problem we should solve. Adding to this, a trivial feedback was also about pigment color. The color of a human fetus is more various than we could imagine, so the pigment color should be either fluorescence or color that cannot appear on the normal human fetus.

Based on the feedback we received from the Gold Biome, we could think about practical problems that could occur when commercialized and resolution for them.

Consulting with Gut Microbiome Specialist

An interview with professor Kim Hui Nam, who majors the rumen microorganism was our first attempt to get advice regarding our project, POO-robiotics, and simultaneously an approach to see our project in academic perspective from outside, as one of our efforts to inspect our idea in three kinds of perspective- scholar, businessman, and patients.

Our major interest was whether our project has practicality, reliability, and feasibility. After we presented our project, professor Kim expressed his concern that the pigment method is not much feasible since it is hard for one to distinguish the color of the pigment expressed by microorganism and foods that a person ate if those two has a similar color. What he pointed out was that the problem is not about the expression itself but how to make a significant amount of expression enough to be detected by a naked human eye.

Discussion with professor helped us to deduce three solutions. One was to consider the method for an uptake of ‘POO-robiotics’. We expected that If patients avoid certain foods that have the high opportunity of confusing, there would be much higher chance of an accurate detection. Another was to use another signaling method, which is the fluorescence method. Instead of expressing pigment, we decided to manipulate Lactobacillus to express fluorescence. Unlike pigments, fluorescence proteins can be clearly distinguished under UV conditions. In addition, the fact that fluorescent proteins do not require precursor is one of its strength. The last was to design a signal-amplification pathway. We thought of using microorganism’s quorum sensing molecule, which was beyond our capacity to prove results by experiments. So, instead of performing the actual experiment, we incorporated our concept into the modeling to compare the outcomes.

We also asked about the intaking method of the Lactobacillus. Since our project’s major goal was to make easily consumable probiotics, using capsules were not acceptable for it has no difference with the conventional approach. What we have previously thought was to make it as dairy products, like yogurt. However, there was a general concern whether lactobacillus can safely reach the intestine, through stomach acids. Professor’s explanation was that, even though some of the probiotics die, rest of them would eventually reach the intestine and fully function as they designed. Besides, oral intake is what many of commercial probiotics has adopted.

So, in the aspects of academia, we could solve the signal-expressing problems and devise the means of probiotic consumption. Our goal here was focused on the materialization of the idea, not considering things such as economic feasibility nor convenience.

Visiting Microbiology Lab at Anam Hospital

While we were working on a collaboration with other teams about legislations of GMM, we found out that current regulations are very limited for scientific progress. Moreover, throughout our visit to the public health center and hospital for an occult blood test, we checked how current tests are executed and their limitations.