In August 2025, our research team—focused on developing probiotic-based interventions for hyperuricemia—visited the Second Affiliated Hospital of Anhui University of Chinese Medicine, a renowned institution integrating traditional Chinese medicine (TCM) and modern clinical practice. During this visit, we conducted an in-depth interview with Chief Physician Jiang Liushun from the Rheumatology and Immunology Department, who has over 20 years of clinical experience in managing metabolic diseases like hyperuricemia and gout. This interview aimed to bridge the gap between TCM wisdom and our ongoing GoutBuster project, seeking insights to refine both our experimental protocol and Human Practice initiatives.

Prior to this hospital visit, our team’s understanding of TCM remained superficial. Most of us had only encountered TCM through public knowledge—limited to basic therapeutic techniques such as acupuncture (inserting fine needles into specific acupoints to regulate qi flow) and cupping (creating suction on the skin to alleviate muscle tension)—and lacked systematic awareness of TCM’s theoretical framework, such as the concepts of “yin-yang balance” and “meridian circulation.” Given this knowledge gap, and aligned with the core objective of our GoutBuster project (developing engineered probiotics to manage hyperuricemia), we formulated targeted questions for Dr. Jiang, with a particular focus on: “What unique strategies does TCM employ for the prevention and clinical treatment of hyperuricemia, and how might these approaches complement modern biotechnological interventions?”

In response to our inquiry, Dr. Jiang began by elaborating on TCM’s holistic diagnostic paradigm, emphasizing that hyperuricemia, like other diseases in TCM, is not treated as a uniform condition but classified into distinct syndromic types based on the “Four Diagnostic Methods” (Si Zhen)—a cornerstone of TCM practice. Specifically, “observation” involves assessing patients’ facial complexion (e.g., a reddish complexion may indicate internal heat accumulation), tongue coating (thick yellow coating often suggests damp-heat in the body), and physical posture (stiff joint movements may signal qi and blood stagnation); “auscultation-olfaction” focuses on abnormal breathing sounds or body odors (e.g., a sour smell might relate to digestive imbalance); “inquiry” entails detailed questioning about symptoms (such as the timing of joint pain, dietary habits, and sleep quality); and “pulse-taking” involves palpating radial pulses to gauge the state of qi, blood, and internal organs (a rapid, forceful pulse often correlates with excess heat). Based on these assessments, Dr. Jiang explained that hyperuricemia is typically categorized into three main syndromic types in clinical TCM practice: damp-heat obstruction (characterized by acute joint swelling and pain), qi-blood stagnation (manifested by chronic joint stiffness), and deficiency of the liver and kidney (common in elderly patients with recurrent gout).

“Treatment must be tailored to the syndrome,” Dr. Jiang emphasized. For patients in the latent stage of hyperuricemia—those with elevated serum uric acid but no obvious joint symptoms—TCM prioritizes herbal conditioning to regulate metabolism and prevent disease progression. Common herbal formulas include Simiao Powder (composed of Atractylodes lancea, Phellodendron chinense, Coix lacryma-jobi, and Achyranthes bidentata), which clears damp-heat and promotes uric acid excretion through diuresis. For patients experiencing acute gout attacks (a typical presentation of the damp-heat obstruction type), TCM combines internal herbal administration with external interventions to rapidly relieve pain: hot compresses using herbs like Angelica sinensis and Ligusticum chuanxiong improve local blood circulation, while tuina (Chinese therapeutic massage) targeting specific acupoints (such as Sanyinjiao and Zusanli) helps alleviate muscle spasms. Notably, Dr. Jiang highlighted that TCM’s personalized approach extends beyond symptom management: “We do not rely solely on traditional diagnostic indicators. We also monitor patients' gastrointestinal health—for example, whether they experience bloating or irregular bowel movements, as digestive function directly affects purine metabolism—and even their work efficiency, which reflects overall qi and blood status. Integrating these factors allows us to adjust treatments more precisely.”

Dr. Jiang's detailed explanation provided our team with profound insights, particularly regarding the convergence of TCM and modern medicine in core philosophy. While TCM and modern medicine differ drastically in their treatment tools—TCM uses herbs, acupuncture, and tuina, whereas modern medicine relies on synthetic drugs and biotherapeutics—both adhere strictly to the principle of “accurate diagnosis and precise treatment.” This realization prompted us to reflect on a critical limitation in our GoutBuster project's initial design: our mathematical modeling team had initially proposed calculating the daily probiotic dosage solely based on patients' height and weight, a one-size-fits-all approach that overlooked individual variability. Dr. Jiang's emphasis on personalized TCM treatment reminded us that hyperuricemia management is far more complex: factors such as a patient's underlying health status (e.g., whether they have comorbidities like renal insufficiency), intestinal absorptive capacity for purines and probiotics (influenced by gut microbiota composition), and even lifestyle habits (e.g., dietary preferences) all significantly impact the efficacy of probiotic interventions. For instance, patients with impaired renal function may require lower probiotic doses to avoid potential metabolic burdens, while those with slow intestinal transit may need adjuvant measures to enhance probiotic colonization. Incorporating these physiological indicators into our dosage calculation formula, we realized, would enable us to develop more accurate, patient-specific medication guidelines—aligning our project with the “precise treatment” ethos shared by both TCM and modern medicine.

The interview also yielded valuable insights into hyperuricemia prevention, an area often overlooked in modern clinical practice but emphasized in TCM’s “preventive treatment of disease” (Yu Fang Zhi Bing) concept. Beyond conventional recommendations—such as limiting high-purine foods (seafood, animal offal, beer) and regular serum uric acid monitoring—Dr. Jiang specifically highlighted tai chi, a traditional Chinese martial art with a history of over 400 years, as an ideal preventive exercise for hyperuricemia. “During the latent stage, patients may not feel joint pain, but their metabolic system is already imbalanced,” she explained. “Intense exercises like running or weightlifting can increase purine catabolism and trigger gout attacks, whereas tai chi—with its principles of ‘calm mind, relaxed body, and uniform movement’—promotes gentle energy flow and improves microcirculation without straining the body. Long-term practice also regulates the autonomic nervous system, which indirectly supports uric acid metabolism.”

This suggestion resonated strongly with our team, as East China University of Science and Technology (ECUST) offers a specialized tai chi course as part of its physical education curriculum—designed to integrate traditional culture with health promotion. Inspired by Dr. Jiang’s advice, we have since developed a collaborative plan with the course instructor: we will revise the curriculum to include modules on hyperuricemia prevention, where students will learn about the disease’s risk factors and TCM’s preventive strategies while practicing tai chi. For example, during warm-up exercises, instructors will explain how tai chi’s slow, controlled movements benefit purine metabolism; during cool-down sessions, we will introduce our GoutBuster probiotic project, explaining how engineered probiotics complement TCM by targeting intestinal purine absorption. This “education-through-sport” approach not only raises awareness about hyperuricemia among ECUST students of all majors but also enhances the public engagement impact of our project—turning a routine physical education class into a platform for combining traditional health wisdom with cutting-edge biotechnology.

In summary, this interview with Chief Physician Jiang Liushun was a pivotal milestone for our GoutBuster project. It not only deepened our understanding of TCM’s holistic approach to hyperuricemia management but also provided actionable guidance to refine our project design—from optimizing probiotic dosage calculations to developing innovative Human Practice initiatives. By bridging TCM’s personalized treatment philosophy with modern synthetic biology, we aim to develop more effective, patient-centered solutions for hyperuricemia, ultimately contributing to the integration of traditional and modern healthcare practices in metabolic disease management.

In May 2025, at the initial stage of our research project focused on hyperuricemia intervention, our team conducted a special interview with a senior physician from the Department of Internal Medicine at Nanjing Hospital of Traditional Chinese Medicine. The primary objectives of this interview were to gain in-depth insights into the commonly used clinical treatment methods for hyperuricemia, identify the practical dilemmas faced in therapeutic practice, and explore how our research project could address these unmet clinical needs. Below is a detailed account of the interview content and the inspiration it provided for our project.

The physician began by sharing key observations from clinical practice, particularly regarding the challenges in treating patients with refractory gout—a severe form of hyperuricemia characterized by recurrent, difficult-to-manage symptoms. He noted that traditional urate-lowering drugs such as allopurinol sometimes fail to achieve the desired therapeutic outcomes in these patients. However, he was careful to clarify a critical misconception: unlike antibiotics, which can induce drug resistance in bacteria through prolonged use, gout medications (including allopurinol, febuxostat, and benzbromarone) do not trigger “typical drug resistance” in the conventional sense. The “treatment failure” mentioned in clinical settings, he explained, primarily falls into two categories: suboptimal treatment response and actual therapeutic ineffectiveness.

On one hand, drug-related adverse reactions often become a major barrier to sustained treatment. For instance, allopurinol—one of the most widely used xanthine oxidase (XO) inhibitors—can induce severe hypersensitivity reactions in 0.4% to 2% of patients. These reactions range from mild skin rashes and fever to life-threatening conditions such as Stevens-Johnson syndrome, a rare but devastating skin disorder. Such adverse events often force clinicians to discontinue allopurinol prematurely, even if the drug initially showed promise in lowering serum uric acid levels. On the other hand, comorbidities in patients further complicate treatment efficacy. The physician emphasized that a significant proportion of hyperuricemia patients also suffer from renal insufficiency, metabolic syndrome, or hypertension. These concurrent conditions not only disrupt the body’s normal purine metabolism and uric acid excretion pathways but also require the use of auxiliary medications—such as diuretics for hypertension or insulin for diabetes—that can interfere with renal uric acid excretion. For example, loop diuretics like furosemide reduce the reabsorption of water in the renal tubules, which inadvertently increases the reabsorption of uric acid, thereby weakening the urate-lowering effect of gout medications.

A particularly noteworthy point raised by the physician was the issue of uric acid precursor (xanthine) accumulation caused by existing therapies. He explained that the current mainstream treatment for hyperuricemia relies heavily on XO inhibitors, which work by blocking the final step of uric acid synthesis: the conversion of xanthine to uric acid. While this mechanism effectively reduces uric acid production, it also leads to the gradual accumulation of xanthine in the body—a pharmacological phenomenon that is often overlooked but carries potential toxicity risks. For patients with normal renal function, the kidneys can typically excrete excess xanthine without obvious complications. However, in patients with renal insufficiency, the reduced renal excretion capacity means that high-dose XO inhibitor use can cause xanthine to crystallize in the renal tubules, forming rare but severe xanthine stones. In extreme cases, this crystallization can further induce acute renal injury, creating a vicious cycle where treatment for hyperuricemia inadvertently damages kidney function. This not only reduces patients' tolerance to long-term treatment but also undermines the sustainability of therapy.

More critically, the physician highlighted a fundamental limitation of existing hyperuricemia medications. He elaborated that current drugs either block the final step of uric acid synthesis (“xanthine → uric acid”) or promote the excretion of already formed uric acid (e.g., benzbromarone, which inhibits renal uric acid reabsorption). However, none of these approaches can effectively reduce the total pool of purine nucleotides in the body or the precursor load (hypoxanthine and xanthine) generated by purine catabolism. This explains a common clinical phenomena that most patients require long-term or even lifelong medication to maintain normal serum uric acid levels—once treatment is discontinued, the body's continuous production of purine precursors quickly drives uric acid levels back to pathological ranges.

This detailed explanation from the physician sparked a brand-new idea within our research team: if blocking the metabolic pathway from purines to uric acid only leads to the accumulation of harmful purine precursors, could we instead develop a strategy to directly ABSORB these precursors (especially xanthine) and TRANSPORT them out of the body before they are converted to uric acid?

Prior to the interview, our team had conducted extensive literature reviews, which revealed that purines—whether from dietary intake or endogenous metabolism—are primarily absorbed in the intestinal tract before entering the bloodstream and being metabolized to uric acid. The key term “intestinal tract” immediately directed our thinking toward a novel intervention approach: intestinal probiotics. We hypothesized that if we could use gene-editing technology to engineer a probiotic strain capable of absorbing purines (such as xanthine and hypoxanthine) in the intestinal tract and transporting them out of the body via feces, this strategy would address two critical shortcomings of traditional treatments: it would avoid the renal side effects associated with conventional drugs (which target the kidneys for uric acid excretion) and prevent the accumulation of purine precursors in the body—effectively achieving “two goals with one approach.”

We shared this conceptual framework with the physician, who expressed strong approval and encouragement. However, he also candidly outlined the practical challenges that our proposed approach might face in clinical translation. He noted that live biotherapeutic products (LBPs)—a category that includes engineered probiotics—are currently not widely used in clinical practice, primarily due to unresolved issues in safety, efficacy consistency, and public acceptance. In terms of safety, the most significant concerns include the risk of horizontal gene transfer: if the engineered probiotic strain carries exogenous functional genes (e.g., genes encoding xanthine transporters), there is a theoretical possibility that these genes could be transferred to other indigenous gut microorganisms, potentially altering the normal metabolic balance of the gut microbiota. Additionally, LBPs may trigger adverse reactions such as allergies (especially in patients with a history of food allergies) or localized intestinal infections (particularly in immunocompromised individuals). Beyond technical challenges, the physician also pointed out that public acceptance of gene-edited microbial products remains low, with many patients harboring concerns about “genetically modified organisms” (GMOs)—a sentiment that could hinder the clinical adoption of our probiotic-based intervention.

Armed with this refined research direction and a clear understanding of the pending challenges, our team actively sought collaboration with experts from the State Key Laboratory of Bioreactor Engineering (SKLBE) at East China University of Science and Technology (ECUST). SKLBE has a long-standing research focus on engineered probiotics, with established platforms for microbial gene editing, strain characterization, and safety assessment. After presenting our research concept to the SKLBE team, we formally launched a collaborative project focused on developing “purine-transporting probiotics.”

Over the subsequent months of project implementation, we specifically addressed the safety concerns raised by the physician. Our Human Practice team designed and distributed a public survey to collect opinions and improvement suggestions regarding gene-edited pharmaceutical products. Those data were promptly shared with our experimental team, which then implemented a series of targeted safety measures: first, we conducted rigorous gene transfer assays to verify that the exogenous xanthine transporter genes in our engineered probiotic strain could not be transferred to other common gut bacteria (such as Escherichia coli and Bacteroides fragilis); second, we removed the antibiotic resistance genes from the probiotic’s expression vector to eliminate the risk of antibiotic resistance gene dissemination. These safety validation steps are detailed in the “Wet Lab” section of our project report.

In summary, this interview with the senior physician from Nanjing Hospital of Traditional Chinese Medicine was a pivotal turning point for our research project. It not only clarified the limitations of existing hyperuricemia treatments but also provided the critical inspiration needed to shift our research focus toward intestinal probiotic engineering. Moreover, the physician's insights into the challenges of LBP clinical translation guided us to proactively address safety and public acceptance issues—ensuring that our research remains grounded in real-world clinical needs while advancing innovative biotechnological solutions.

In July 2025, the early stage of our project, our team visited Shanghai InnoGeco Biotechnology Co., Ltd., a company specializing in microbial preservation and fermentation technologies. The purpose of this visit was to better understand strain preservation techniques and to discuss the scaling-up process for engineered strains—two critical steps for bridging laboratory research with practical applications.

During the visit, the InnoGeco team introduced us to the principles and practices of strain preservation technology. They emphasized that reliable long-term preservation is essential for maintaining genetic stability, viability, and functionality of engineered strains, especially when considering downstream applications in live biotherapeutic products. This knowledge helped us design our own experimental workflow with an early focus on stability and safety.

The discussion then turned to the strain scale-up process. InnoGeco scientists explained how laboratory-scale cultures differ significantly from industrial-scale fermentation in terms of oxygen transfer, nutrient supply, and contamination risk. They highlighted the importance of controlled bioprocess design, including bioreactor optimization, sterilization procedures, and quality control checkpoints. These insights gave our team a clearer picture of how future translation of engineered probiotics would require not just genetic design, but also robust production pipelines.

This visit was particularly valuable for our project because it grounded our experimental work in real-world technical practices. By learning directly from industrial experts, we were able to anticipate potential challenges in strain stability and large-scale production, ensuring that our design philosophy was aligned not only with biological innovation but also with practical feasibility.

In July 2025, during the early stage of our project, our team visited Bright Dairy & Food Co., Ltd., one of the leading enterprises in the dairy industry. The purpose of this visit was threefold: to gain a better understanding of the current dairy and probiotic market landscape, to learn about practical techniques in probiotic product preparation, and to consult industry experts on the development prospects of the probiotic sector.

The Bright Dairy team first introduced us to the current probiotic market. They explained how probiotics have become an essential element in functional dairy products, with consumer demand increasingly focused on health benefits, safety, and scientific credibility. This overview helped us recognize the strong market potential and consumer interest in probiotic-based interventions.

We then discussed the technical aspects of probiotic preparation. Bright Dairy experts explained key steps such as strain cultivation, encapsulation, stabilization, and product formulation. They highlighted the importance of maintaining strain viability throughout processing and storage, which directly determines product quality and consumer trust. For our project, this provided important practical insights into how engineered probiotics might be manufactured and delivered in future applications.

Finally, the company shared their view on the future prospects of the probiotic industry. They emphasized that the field is moving beyond traditional health foods toward more scientifically grounded, clinically validated live biotherapeutic products (LBPs). This perspective confirmed that our research direction—engineering probiotics for uric acid control—fits within an emerging frontier of the industry where scientific innovation and consumer demand intersect.

This visit gave us valuable inspiration in connecting our lab-based research to real-world industry practices. By learning from Bright Dairy’s experience in probiotic product development, we gained both technical knowledge and market awareness, which will guide us as we consider the translational potential of our engineered probiotic design.

In September 2025, at the later stage of our project, our team visited Shanghai Baoteng Biotechnology Co., Ltd., a company at the forefront of live biotherapeutic drug innovation. The primary objectives of this interview were to understand how enterprises are strategically planning in the field of live biotherapeutics, how AI technologies are being integrated into precision medicine, and how industry-academia-clinical collaboration is shaping the future of preventive healthcare.

During the discussion, the Baoteng team shared their perspective on the original innovation of live biotherapeutic products (LBPs). They emphasized that while the global market for LBPs is rapidly expanding, long-term competitiveness requires independent innovation in strain design, safety evaluation, and delivery technologies. This resonated deeply with our project’s core ambition to engineer probiotics that could intervene in purine metabolism at an early stage.

A second key theme was the integration of AI in precision medicine. Baoteng scientists highlighted how AI-driven platforms are being used to model complex biological interactions, predict patient responses, and optimize clinical trial design. They noted that AI not only accelerates discovery but also helps bridge the gap between laboratory innovation and real-world application. For our team, this provided strong inspiration to explore computational modeling as a tool to predict the safety and efficacy of engineered probiotics in diverse patient populations.

The company also underscored the importance of collaborative innovation across industry, academia, research institutes, and clinical practice. They described how successful LBP development requires a synergistic ecosystem: academia to provide cutting-edge scientific breakthroughs, enterprises to drive translational development and regulatory strategy, and clinical partners to validate safety and therapeutic value in real-world settings. This vision of integrated collaboration echoed with our own approach to Human Practices, in which we seek to weave together voices from patients, clinicians, and industry partners to guide project design.

This interview reinforced a crucial insight for our team: engineered probiotics for uric acid control cannot exist in isolation as a laboratory concept. Instead, they must be conceived as part of a broader ecosystem that unites scientific creativity, technological enablers such as AI, and cross-sector collaboration. By embedding these principles into our project, we not only align with the current trajectory of the biotherapeutics industry but also ensure that our work remains meaningful and applicable in the context of future preventive healthcare.

On September our iGEM team members visited Xellar Biosystems, a pioneering enterprise in biotech automation and organ-on-chip technology. The visit focused on exploring cutting-edge life science automation and potential collaborations for interdisciplinary innovation.

During the visit, the company's leadership introduced their breakthroughs in automation and AI-integrated biotechnology platforms. They demonstrated China's first AI-driven intelligent cell culture system and shared their extensive collaboration network with top pharmaceutical companies and academic institutions.

The company also underscored the importance of collaborative innovation across industry, academia, research institutes, and clinical practice. They described how successful LBP development requires a synergistic ecosystem: academia to provide cutting-edge scientific breakthroughs, enterprises to drive translational development and regulatory strategy, and clinical partners to validate safety and therapeutic value in real-world settings. This vision of integrated collaboration echoed with our own approach to Human Practices, in which we seek to weave together voices from patients, clinicians, and industry partners to guide project design.A significant part of the discussion revolved around the application of organ-on-chip technology for validating engineered probiotics - a key focus of our iGEM project. The experts elaborated on how organoid models can simulate human intestinal environments to assess the efficacy, safety, and host-microbe interactions of probiotic strains. This approach provides a more physiologically relevant alternative to traditional in vitro tests and animal models.

This visit provided crucial insights into how advanced organoid and automation technologies can bridge the gap between laboratory research and real-world applications. By integrating these methodologies, our team can enhance the robustness and translational potential of our engineered probiotics, ensuring they meet both scientific and industrial standards.

We are excited about the potential collaboration opportunities. The expertise in organ-on-chip technology and automated systems could greatly accelerate the validation phase of our project, bringing us closer to developing a reliable and effective solution for managing hyperuricemia.

Through face-to-face conversations with patients suffering from hyperuricemia and gout, we gained a deeper understanding of their daily struggles. Many described the heavy financial burden of long-term medication, the difficulty of maintaining strict dietary restrictions, and the frustration of poor or delayed treatment outcomes. Despite these challenges, patients expressed openness to new approaches, especially the potential of engineered probiotics as a safer, more affordable, and sustainable alternative.

One interview with “Qianqian,” an alumnus of ECUST, revealed several important insights: hyperuricemia is not only triggered by purine-rich foods but also by sugary drinks like those containing fructose; animal-derived purines pose greater risks than plant-based ones; and hereditary factors can predispose even young people to high uric acid levels. Above all, he emphasized that safety must come first—patients are willing to accept moderate efficacy if treatments avoid liver and kidney risks.

These perspectives reminded us that behind every clinical statistic is a personal story. They also reinforced our project’s priorities: to focus on rigorous safety validation, highlight hidden dietary risks in public education, and design solutions that not only advance scientific innovation but also genuinely improve patients’ quality of life.