In the early and middle stages of the project, our team conducted in-depth interviews and research with individuals related to inflammatory bowel disease (IBD), including researchers and patients. Through these exchanges, we have learned about the relentless pursuit of researchers in exploring the pathogenesis and drug action mechanisms of IBD, as well as the pain and inconvenience that patients endure in their daily lives. This profound understanding makes us realize the urgency and importance of researching and treating Crohn's disease and ulcerative colitis not only in the scientific field, but also at the societal level. Through interviews and research with IBD related personnel, we have not only deepened our understanding of the pathogenesis and treatment status of IBD, but also enhanced our sense of awe towards our work. This process not only enhances the scientific and social significance of our team's project, but also provides valuable guidance and inspiration for future research directions.
Department of Microbiology, College of Life Sciences, Nankai University, Tianjin 300071, China.
Interviewee: Xiao Huiwen, Nankai University
Zhang：Nowadays, intestinal health issues are receiving increasing attention. What do you think is the biggest misconception or blind spot for the public in terms of intestinal health?
Xiao：Let's start with the people around me. Some of my relatives and friends may have some intestinal problems to some extent, such as constipation or diarrhea. Most people may choose yogurt or use some probiotics. But we know that the number of live bacteria in yogurt may be unstable, and there are many types of probiotic drugs on the market with varying qualities. So the main problem now is that the public doesn't know what standards to use to select these products, nor do they know what products are suitable for themselves. In addition, the relevant departments lack certain experience in the control of these probiotic drugs, and the public also lacks knowledge in this area, which can easily be influenced by misleading propaganda.
Zhang:Indeed, I often encounter these problems in my daily life and find it difficult to choose probiotic agents. I don't know which one is more suitable for me. In addition, IBD has gradually become a highly regarded research direction in the biomedical field. Can you briefly explain the relevant experiments in your laboratory?
Xiao：Our laboratory recently found a small molecule protein in Cordyceps sinensis, which can alleviate the damage to the intestine and hematopoietic system caused by ionizing radiation. The specific mechanism is that this protein can activate our immune system, regulate the activity of B lymphocytes, and thus achieve the effect of relieving intestinal damage and inflammation.
Zhang：Do you think it is feasible to design engineered bacteria using synthetic biology to treat intestinal diseases? What is the difference between it and traditional medicine?
Xiao：According to current research, it is feasible, but in terms of clinical application, I have always been concerned about whether 2.this engineered bacteria can enter our bodies in a controllable way? After entering the intestine, how long will it be cleared? Or will it continue to be expressed, thereby disrupting the intestinal homeostasis? I'm worried about this kind of problem. Did you consider this aspect when designing this engineering bacterium?
Zhang:We have indeed taken this factor into consideration. At the beginning of the project design, we thought that if we only expressed anti-inflammatory factors, engineered bacteria would definitely not be as safe as targeted drugs. Then, in the subsequent process, we tried to add reactive oxygen species activation factors to achieve controlled expression in space. In addition, there is the role of adhesion factors. We identified the diversity of gut microbiota and found that increasing adhesion factors can improve the diversity of gut microbiota, as well as improve the structure of gut microbiota and increase the colonization of beneficial bacteria. Overall, we have made some attempts in this area, but of course, there is still a long way to go before this engineered bacterium can be transformed into a marketed drug. We will definitely not be able to achieve perfection within this short competition period, and there are still many problems to be solved.
Then you can talk about it. What are the differences between our engineered bacteria and traditional drugs?
Xiao: I think the difference between probiotic preparations and traditional medicines is that their effects after entering the body may be multifaceted. Traditional drugs can generally find specific targets of action, but after entering the body, fungal preparations can exert their effects through metabolites and interact with other bacteria, causing changes in the gut microbiota at the community level and producing many unforeseen effects. In addition, the repeatability of the action of fungal preparations is influenced by many factors, which may lead to significant differences in the effectiveness of drugs among different individuals, while traditional drugs have fewer problems in this regard.
Zhang: When we initially designed the experimental content, we also considered exploring the impact of engineered bacteria on gut microbiota at the community level, including colony diversity, metabolome changes, etc. However, considering time and funding factors, we ultimately did not delve into this aspect of influence. Perhaps after the completion of this competition, we can increase relevant experiments in this area, and preferably change the strain carrier to a safer and more reliable one.
I’ve introduced our experimental design to you earlier, which mainly involves using synthetic biology to design engineered bacteria that can colonize and secrete anti-inflammatory factors in the intestine to treat intestinal inflammation. Do you have any suggestions for our design?
Xiao：I suggest that you can also construct a developing element to visually demonstrate through slicing that your engineered bacteria can colonize in the intestine. You can also replace the strains with edible probiotics, which may provide more benefits while ensuring safety. In addition, the changes in the content of Salmonella in the intestinal tract of mice before and after the use of engineered bacteria can be detected to better characterize the function of your engineered bacteria.
Zhang：Okay, okay, thank you for your suggestion. We have one final question. If an engineering bacterium based on a similar approach is successfully developed, would you recommend it to people around you? What kind of people do you think are suitable for using such engineered bacteria?
Xiao:If it can be successfully launched in the end, I may recommend it because my family has also been eating probiotics that have not been modified. If it can eventually become a product, it means that a series of biosafety experiments have been conducted and are effective before that, so I may recommend it.
As for what kind of population may be suitable for such engineered bacteria, the number of patients with inflammatory bowel disease is actually increasing, and the use of antibiotics is also a common treatment method, which involves the problem of antibiotic abuse. Therefore, I believe that such probiotics may be suitable for those who have been taking probiotics for a long time and their gut microbiota has been destroyed. Perhaps they can maintain or even increase their gut microbiota diversity while treating the disease. In addition, I have been working on radiation related enteritis before, and some patients in this area are actually taking unmodified probiotics. Currently, I have not seen any engineered bacteria similar to what you have developed on the market. Therefore, if you really succeed in research and development, I think this group of patients is also suitable for use.
Zhang：Our interview questions have probably come to an end. Thank you very much for taking the time to participate in our interview today.
Interviewee: Xiao Zhou, a college student from Hangzhou, Zhejiang, has been troubled by diarrhea for many years and has been suffering from Crohn's disease for four months
Z：When were you diagnosed with Crohn's disease? Can you briefly introduce the symptoms and development of the disease?
X：The diagnosis was made on September 4th of this year. When I was in high school, my stomach was not very good and I often had diarrhea. At that time, I only had one or two times a day and didn't pay much attention to it. I started experiencing diarrhea and abdominal pain around June this year. The frequency is about four to five times a day, and sometimes I get up in the middle of the night to go to the bathroom.
Later on, there was some rectal bleeding, so I went to the hospital for treatment. The diagnosis was gastroenteritis after only drawing blood, so I prescribed some anti-inflammatory drugs. After taking them, the abdominal pain decreased and the frequency of diarrhea decreased, but it has not yet returned to normal. Around the end of June, I developed an oral ulcer and went to the hospital for some unknown reason. At that time, I had no knowledge of Crohn's disease and did not think about it. I thought it was a common illness because the ulcer had decreased in food intake and abdominal pain began to appear again.
I went home to see a doctor during my vacation in July, and after blood and stool tests, I also took antibiotics. However, there was still no improvement in August, so I went to do a colonoscopy as recommended by the doctor. The first result of colonoscopy showed that there were many ulcers in the intestine, and the preliminary diagnosis was ulcerative colitis. As I had it done at a hospital in Shaoxing, the doctor suggested that I go to Zhejiang University First Hospital for another examination. At the end of August, I went to the First Hospital of Zhejiang University for many examinations. As I had just undergone colonoscopy, I only showed the previous report to the doctor, so the diagnosis was still ulceration. I was hospitalized for a few days and only used mesalazine before being discharged and sent home.
During hospitalization, the diarrhea persisted. After being discharged and returning home, I ate some noodles. Over the next few days, the diarrhea worsened and I also experienced abdominal pain. At this time, I had to pull 7-8 times a day, and I was very weak. Then I went to the hospital and underwent a gastroscopy, which confirmed that I had Crohn's disease. After using hormones for three days, the symptoms of diarrhea and abdominal pain were relieved. On September 13th, I took my first dose of Infliximab for Injection, and now I take it twice a day without any discomfort. I drink Enteral Nutritional Powder every day.
Z：What impact does illness have on your quality of life? (such as work, social activities, etc.)
X：I am still a college student now, and due to hospitalization and long-term severe diarrhea causing low blood pressure, anemia, etc., I had to take a leave of absence for all the courses in the first two weeks of school. Unfortunately, my friends who used to eat together socially were unable to eat together for a long time afterwards, but playing games together did not affect it. It also forced me to stop staying up late and ordering takeout in the future, which can make my lifestyle healthier to some extent.
Z：Will the diagnosis bring you some psychological pressure?
X：As soon as I was diagnosed, I felt very sad and under a lot of psychological pressure. I couldn't eat my favorite foods like fried chicken anymore, and I wondered if it would affect my job search in the future. I've figured it out now, so I just go to the hospital regularly for injections and check ups. I still have to live a normal life, but I need to pay attention to my diet.
Z：If our designed engineering bacteria are found to have good anti-inflammatory effects and safety after extensive experimental verification, and can be successfully marketed through testing by the drug regulatory authority, would you be willing to use them? Or you can also talk about your concerns about these modified biopharmaceuticals
X：I would be willing to use it, but my concern is that if drug resistance develops, it may no longer be applicable. However, there are many types of biologics available now, and it is unlikely that all methods will fail. I also hope that in the future, there will be more solutions that can treat or even completely cure Crohn's disease
Z：What are your expectations for future treatment? From the patient's perspective, what aspects would you like researchers to focus on?
X：I hope local hospitals can pay more attention to the diagnosis and suspicion of Crohn's disease, and reduce some misdiagnosis as ordinary diarrhea that delays treatment. I hope there will be more efficient and convenient treatment methods using bacterial strains and biological agents in the future. My symptoms were actually detected relatively early. The control of Infliximab for Injection is effective, and I can also drink Enteral Nutritional Powder by myself. Many patients need nasal feeding and surgery, which are more uncomfortable and take longer to recover.
As for scientific research, I would prefer researchers to focus on the long-term maintenance of treatment effects, which can help Crohn's disease patients return to a normal diet without too many dietary restrictions.
Z：Mmm, okay, okay. Thank you very much for your cooperation today. It has taken you so long. I hope you can recover soon and have a happy life.