Team:SUSTech Shenzhen/Implementation

  • SUSTech_Shenzhen

    • Implementation

    Implementation of the designed biological system

    About Implementation

    CONTENT

    Overview

    The proposed end-users
  • People who need to prevent predictable diarrhea, including menstrual diarrhea, stress diarrhea, etc.
  • People in areas with poor hygiene and medical conditions
  • Acute diarrhea caused by bacterial infection, take cholera as an example
  • Elderly people who need to take multi-type medicines
  • Special groups who reject medicines Popular science

    • Popular science

    Safety

    Follow-up risk control

    Reference

    Overview

    Diarrhea is a common illness in the world. In 2010, Diarrhea cause approximately 0.801 million deaths of children in the first 5 years of their life (UR 0.555–1.182 million), accounts for 10.5% of all death under 5 years of age, more than AIDS, malaria, and measles combined1,2. Additionally, as the COVID-19 pandemic outbreak worldwide, the number of diarrhea cases increases. According to the research data regarding clinical characteristics of 1099 patients with laboratory-confirmed COVID-19, 3.8% of patients develop a symptom of diarrhea3.

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    Diarrhea can cause great inconvenience to people's lives, and severe cases may lead to death. The main cause of diarrhea-related death is dehydration and infection. The engineering microbiome we designed has the functionality of retaining water and killing pathogenic bacterium-caused diarrhea. We want to help deal with diarrhea in a patient-friendly way.

    The proposed end-users targeted by our products are:

  • Patients with unexplained diarrhea and long-term diarrhea

  • Toddlers who have difficulty taking common drugs

  • People who need to prevent predictable diarrhea, including menstrual diarrhea, stress diarrhea, etc.

  • People in areas with poor hygiene and medical conditions

  • Acute diarrhea caused by bacterial infection, take cholera as an example

  • Elderly people who need to take multi-type medicines

  • Special groups who reject medicines Popular science

    • Patients with unexplained diarrhea and long-term diarrhea

    In our initial social survey, we collected 791 questionnaire responses from different age groups. The results of the questionnaire showed that after the occurrence of diarrhea, 35.15% of people did not know the cause of their diarrhea, and there are currently a large number of patients with long-term diarrhea who cannot find the specific cause of diarrhea. Regarding the impact of diarrhea on everyone, 50.44% of people think that diarrhea has a greater impact on their studies and life. Our engineered bacteria can help them reduce diarrhea in daily life, thereby alleviating this long-term problem.

    Toddlers who have difficulty taking common drugs

    Young children cannot take pills, capsules, etc., and are also very repulsive of granular drugs. Although there are many drugs on the market that can be mixed into milk powder without affecting the effect of the drug, these drugs will also be rejected by young children because of the taste, and it is difficult to take drugs for relatively long-term to young children. Our engineered bacteria can be added almost odorless in food, and through the regulation of intestinal flora, it can ensure a certain time of action, reduce the number of medications, and have fewer side effects on young children.

    People who need to prevent predictable diarrhea, including menstrual diarrhea, stress diarrhea, etc.

    here are many diarrhea that can be predicted, such as diarrhea caused by menstruation, anxiety, or stress. The patient will know before the occurrence of diarrhea, but if the patient has some important events during the imminent diarrhea period, such as exams, interviews, presentations, etc., the patients will need a drug that can prevent diarrhea in advance to help them avoid trouble. However, there are few such drugs on the market at present. Our engineered bacteria can achieve this effect. By eating in advance, the engineered bacteria can react quickly in the body when diarrhea is about to occur, and reduce the trouble in patients' lives.

    People in areas with poor hygiene and medical conditions

    Worldwide, 780 million individuals lack access to improved drinking water, and 2.5 billion lack improved sanitation4. Diarrhea due to infection is widespread throughout developing countries. In low-income countries, children under three years old experience on average three episodes of diarrhea every year4. In addition to water and food problems in most of these areas, medical and sanitation needs to be strengthened. When in this situation, it is difficult for the patient to get timely medical treatment and pay for the cost of various medications every time they have diarrhea. Our engineered bacteria provide a convenient and cheap way. Because our engineered bacteria can achieve multiple effects of one drug, without taking a large number of drugs at the same time, it can also prevent and self-treat, reducing the more serious consequences caused by worsening diarrhea.

    Acute diarrhea caused by bacterial infection, take cholera as an example

    Every year, 1.3 to 4.0 million cases of cholera, and 21 000 to 143 000 deaths worldwide due to the infection5. Cholera affects both children and adults and can kill within hours if untreated. Symptoms of Cholera include severe dehydration. The main cause of diarrhea-related death is dehydration6. The engineering microbiome the applicants designed has the functionality of retaining water and killing pathogenic bacterium-caused diarrhea. Construction of this engineering bacteria provides a cost-effective method to treat diarrhea. Application of this engineering bacteria will reduce the number of deaths caused by diarrhea and save millions of children's life, especially in medical resource-poor countries such as India, Nigeria, the Democratic Republic of the Congo, Pakistan, and Ethiopia2.

    Elderly people who need to take multi-type medicines

    Many elderly people need to take a lot of drugs for different aspects of treatment due to their health. When they have diarrhea, medication is more difficult due to drug interactions, and the use of multiple drugs results in the elderly forgetting or being unwilling to treat because of bother. However, due to various chronic diseases and various drugs, the proportion of elderly people with diarrhea is relatively high. Our engineered bacteria can achieve the effect of one drug with multiple effects and can reduce the trouble of medication in the elderly, and can also help long-term protection of diarrhea caused by chronic diseases or drug side effects.

    Special groups who reject medicines

    Some special people may be reluctant to take drugs because of psychological or physical problems. When serious diarrhea coming, it may be very dangerous if it is not treated. At the same time, many people are unwilling to go to the hospital for treatment after diarrhea occurs. In our questionnaire statistics, 56.26% of the population does not do any special treatment after diarrhea occurs. Our engineered bacteria can be like the probiotics in yogurt. Patients only need to drink yogurt to achieve the therapeutic effect, thus avoiding some patients' irritation about taking medicine or going to the hospital.

    Popular Science

    Our project is not only to develop a way to help treat diarrhea but also to help the public popularize knowledge about diarrhea. In our questionnaire survey, we found that although diarrhea is a disease that almost everyone can encounter, the public's awareness and attention to diarrhea is still very low. Although 43.24% of people know that diarrhea can lead to death when it is severe, they are almost completely unaware of the cause of death. At the same time, some people usually don't know the cause of their diarrhea, and some people will not take any measures after diarrhea occurs. Although diarrhea is sometimes a disease that the human body can heal on its own, we hope to raise the public's awareness of diarrhea, so that they can respond quickly in the event of accidental acute diarrhea to reduce the possible subsequent harm.

    Safety

  • The bacteria we used is E.coil Nissle 1917, an identified probiotic that is beneficial to the human body. The recombinant model of this strain has been studied in clinical trials to prove its safety7.
  • The antibacterial peptide we want to use is human milk hydrolyzed protein, which can be derived from human milk, and is a bacteriostatic substance secreted by humans when they are breastfeeding, so it is difficult to cause harm to the human body.
  • Many practices are using this kind of flora for treatment, and a large number of known experiments have proved its safety7.
  • Students who were involved in the laboratory experiment had been taught about laboratory safety and trained by the Department of Biology, SUSTech
  • During our experiment, students were required to strictly follow the aseptic rules to ensure a safe environment. Furthermore, students were not allowed to work alone in the laboratory, which means that fellows and faculty helped to guarantee safety in our experimental process.

    • Follow-up Risk Control

  • Taking into account the risks that the engineered bacteria may cause to the environment, our project was going to plan a suicide mechanism. When the bacteria enter the natural environment, they will initiate a suicide program due to changes in pH.
  • Because our engineered bacteria are to be added to food, we will conduct a large number of tests on all aspects to ensure their safety before the subsequent out-of-laboratory production test is required. We will also study relevant laws and policies, such as China's Biosafety Law, Food Safety Law, etc., to ensure that our products are sufficiently safe and approved before conducting follow-up experiments.

    • Reference

    [1]Prevention, C. f. D. C. a. Diarrhea: Common Illness, Global Killer. https://www.cdc.gov/healthywater/global/diarrhea-burden.html (accessed 2015-12-17)

    [2]Liu, L.; Johnson, H. L.; Cousens, S.; Perin, J.; Scott, S.; Lawn, J. E.; Rudan, I.; Campbell, H.; Cibulskis, R.; Li, M.; Mathers, C.; Black, R. E., Global, regional, and national causes of child mortality: an updated systematic analysis for 2010 with time trends since 2000. Lancet 2012, 379 (9832), 2151-61.

    [3]Guan, W. J.; Ni, Z. Y.; Hu, Y.; Liang, W. H.; Ou, C. Q.; He, J. X.; Liu, L.; Shan, H.; Lei, C. L.; Hui, D. S. C.; Du, B.; Li, L. J.; Zeng, G.; Yuen, K. Y.; Chen, R. C.; Tang, C. L.; Wang, T.; Chen, P. Y.; Xiang, J.; Li, S. Y.; Wang, J. L.; Liang, Z. J.; Peng, Y. X.; Wei, L.; Liu, Y.; Hu, Y. H.; Peng, P.; Wang, J. M.; Liu, J. Y.; Chen, Z.; Li, G.; Zheng, Z. J.; Qiu, S. Q.; Luo, J.; Ye, C. J.; Zhu, S. Y.; Zhong, N. S., Clinical Characteristics of Coronavirus Disease 2019 in China. N Engl J Med 2020, 382 (18), 1708-1720.

    [4]Sack, D. A.; Sack, R. B.; Nair, G. B.; Siddique, A. K., Cholera. Lancet 2004, 363 (9404), 223-33.

    [5]Navasa, N.; Rodríguez-Aparicio, L.; Martínez-Blanco, H.; Arcos, M.; Ferrero, M. A., Temperature has reciprocal effects on colanic acid and polysialic acid biosynthesis in E. coli K92. Appl Microbiol Biotechnol 2009, 82 (4), 721-9.

    [6]Ophir, T.; Gutnick, D. L., A role for exopolysaccharides in the protection of microorganisms from desiccation. Appl Environ Microbiol 1994, 60 (2), 740-5.

    [7]Sarate, P. J.; Heinl, S.; Poiret, S.; Drinić, M.; Zwicker, C.; Schabussova, I.; Daniel, C.; Wiedermann, U., E. coli Nissle 1917 is a safe mucosal delivery vector for a birch-grass pollen chimera to prevent allergic poly-sensitization. Mucosal Immunology 2019, 12 (1), 132-144.