OVERVIEW
This project focuses on the prevention and intervention of intestinal microbiota imbalance during the perioperative period. Leveraging synthetic biology technology, we engineered Lactobacillus caseiinto an "intestinal health guardian" probiotic strain—incorporating the p16090 bile acid-inducible promoter, OLE1 oleic acid synthesis gene, accA oleic acid expression-enhancing gene, and DEFB4A defensin gene. This enables precise in-situ secretion of oleic acid within the gut to suppress pathogenic bacteria and modulate immune balance, addressing clinical pain points such as the psychological barriers of traditional fecal microbiota transplantation and the limited efficacy of conventional probiotics.
Beyond technological development, the project establishes a multidimensional framework encompassing "education outreach – inclusive practice – sustainable development – cross-sector collaboration – commercial translation." This system spans knowledge dissemination from campuses to the global community, technology implementation from laboratories to clinical settings, and health empowerment for both vulnerable groups and the general public. The ultimate goal is to narrow healthcare resource disparities, advance health equity, and deliver "Lanzhou University’s solution," "Gansu’s solution," and "China’s solution" for global perioperative intestinal health management.
To efficiently translate the concept into practice, we structured the workflow into three synergistic phases based on synthetic biology research logic and social value realization pathways: the Preparation Phase, Exploration Phase, and Responsibility Phase. These stages progress cumulatively and interconnect seamlessly—the Preparation Phase lays the groundwork for technical and cognitive foundations, the Exploration Phase achieves technological breakthroughs and validates practical applications, and the Responsibility Phase amplifies societal impact and value dissemination. Together, they form a closed loop of "scientific innovation – practice feedback – iterative optimization," ensuring the project integrates scientific rigor with social practicality.
Preparation phase
Guided by a problem-orientedapproach, our team employed a tripartite methodology—literature review, expert interviews, and frontline fieldwork—to define the project’s strategic direction and solidify its implementation foundation. All guiding faculty members \(including university professors\), clinicians, industry experts, and academic scholars contributed specialized insights, offering recommendations that were deeply integrated with both the project’s strategic vision and operational details.
Simultaneously, we established synergistic collaborations with hospitals, enterprises, and community stakeholders, systematically gathering empirical data and actionable improvement proposals. These multi-sectoral engagements provided critical support to bridge the gap between the project’s initial "laboratory concept" and its eventual "real-world application," ensuring the foundational robustness required for subsequent phases.
Project Inspiration: Addressing Clinical Pain Points
The project originated from identifying critical gaps in clinical practice. During their internship at the First Hospital of Lanzhou University, team members observed a prevalent challenge among perioperative patients: intestinal microbiota imbalance. One patient who underwent gastrointestinal surgery developed severe microbiota dysbiosis following antibiotic treatment and fasting stress, manifesting as bloating, infections, and other complications. This not only prolonged hospitalization but also imposed significant financial burdens on the family.
Further investigation revealed substantial limitations in conventional solutions. Fecal microbiota transplantation \(FMT\) required patients to overcome psychological barriers, while the standardized and uniform processing of fecal microbiota preparations remained technically challenging—constraints that hindered its broader application.
During a group discussion, a classmate’s yogurt sparked our interest. "Probiotics," commonly featured in yogurt and health products, are often promoted for their digestive benefits and gut-stabilizing properties. However, the probiotic components in food proved insufficient to resolve microbiota imbalance due to inherent limitations in their quantity and functionality.
The emergence of synthetic biology offered a transformative solution. By genetically engineering probiotics to possess "intestinal-targeted responsiveness" and "multifunctional synergy", we envisioned creating a "living drug" capable of precisely modulating the gut microbiota. Concurrently, the team recognized the unique challenges faced by northwestern China—where Lanzhou University is located—including geographic remoteness, limited economic resources, and shortages of educational and healthcare infrastructure. These factors, coupled with low public awareness of gut health, strengthened our resolve to pursue a dual-track approach combining technological innovationwith knowledge dissemination.
Thus, the "Gut Health Guardian" project was conceived: an engineered probiotic strain-based solution designed to tackle perioperative microbiota imbalance through scientific rigor and accessible health education.
Further Understanding
After recognizing the broad prospects of engineered probiotic strains in treating perioperative intestinal microbiota imbalance, we delved deeper into its significance and feasibility. Our initial step was to visit the First Hospital of Lanzhou University, where we interviewed several physicians from diverse departments—including Professor Yatao Liu and Professor Jianming Tang.
Through discussions with these clinicians, we gained a nuanced understanding of the underlying mechanisms driving perioperative microbiota dysbiosis and the spectrum of available treatment options. In-depth interviews revealed that the core mechanisms of this imbalance involve a triad of factors:
1.Preoperative fasting, which deprives gut microbiota of essential nutrients;
2.Intraoperative traumatic stress, which disrupts the mucosal barrier; and
3.Postoperative antibiotic use, which indiscriminately eliminates both pathogenic and commensal bacteria.
The synergistic impact of these three elements leads to the overproliferation of harmful bacteria, ultimately destabilizing the gut ecosystem.
Beyond physician consultations, we engaged representatives from the target patient population. After clearly explaining our project’s core functionalities, applicable scenarios, and advantages, we patiently addressed their inquiries regarding usage methods, safety profiles, and expected outcomes.
The feedback was unequivocally positive: the patient representative expressed clear interest in utilizing our product and a preference for its selection. This direct response not only validates target users’ acceptance of the solution but also provides some feasibility evidence for the product’s future successful market launch.
To incorporate the business perspective, our team interviewed Mr. Jinghong Liu, the founder of Jinghong Health Products Co., Ltd., a company honored as a "China Preferred Brand."
Mr. Liu pointed out that medical and health products need to balance "technological excellence, scientifically - formulated ingredients, and a brand with soul." Technologically, it is essential to achieve breakthroughs in strain stability and mass - production processes. Formulation - wise, the products should be scientific and suitable for the gut. Regarding the brand, it is necessary to enhance user identification through stories and culture.
He particularly emphasized the importance of intellectual property protection and multi - team collaboration. He suggested that the team should plan patent applications in advance and build a collaborative network of "industry - academia - research - hospital" by joining forces with universities, enterprises, and hospitals. These suggestions have provided crucial guidance for the project's commercial transformation path and brand building.
The team also learned that the global probiotics market has been steadily growing in recent years. According to data from MarketsandMarkets, the global probiotics market size was estimated to be $61.1 billion in 2021. It is expected to continue growing at a compound annual growth rate \(CAGR\) of 8.3% from 2021 to 2026, reaching $91.1 billion by 2026. This market holds significant opportunities.
Exploration phase
After reviewing the relevant literature and conducting preliminary verification that oleic acid affects perioperative gut microbiota imbalance, we realized the necessity of clearly defining the specific application scenarios and positioning of the drug. Against this background, we reached out to bioscience experts, Professor Zhenyou Zhou and Professor Hengliang Lang. After introducing our ideas and uncertainties to them, both professors pointed out significant issues we face and suggested that we could leverage microorganisms to regulate the gastrointestinal tract. They highlighted that synthetic biology has become a popular field in recent years, offering the knowledge required to engineer bacteria, thereby ensuring practicality and economic feasibility. As a result, our team began to study and discuss synthetic biology.
To further advance the project, we interviewed experts in the biosciences and discussed the feasibility and specific details of the project, deepening our understanding of perioperative gut microbiota imbalance. These bioscience experts provided us with many practical and effective suggestions for the issues and uncertainties we encountered during our experimental work. Through dialogues with them, we gained a more profound understanding of our mission and came up with new ideas for the future implementation of the project.
As a project focused on disease treatment, continuous communication with experts and clinicians in relevant fields is crucial. Professor Liu, Professor Zhou, Professor Tang, and Professor Lang have consistently offered us support and care, providing highly constructive advice from project design to problems encountered during experiments.
After fully demonstrating the feasibility and market potential of the project, we contacted AMATHES, a company based in Suzhou, and submitted a detailed project plan. The company’s executives gave high praise and strong support to our project’s development and marketing.
We have also engaged in in-depth discussions with outstanding students from many universities, including Tianjin University \(TJUSLS\_China\), Jilin University \(JLU\-NBBMS\), Ocean University of China \(OUC\-China\), Nankai University \(NKU\-China\), and Zhengzhou University \(ZZU\-iDEC\). We have promoted communication and cooperation between different teams.
Our team also participated in the "China Regional iDEC 'Engineered Living Drugs' Thematic Symposium" initiated by the Peking University iDEC team \(Peking iDEC\).
From August 5th to 9th, 2025, 28 iDEC teams from 24 top-tier universities across China gathered at the Jin Kemu Life Science Building of Peking University to engage in in-depth discussions centered on the "Opportunities and Challenges of Engineered Living Drugs".
Our team also participated in the 12th China iDECer Community Conference & the 2nd Global Bio Developers Conference \(CCIC & Synbiopunk 2025\).
This industry event — which brought together 107 iDEC teams from across China and over 200 registered participants — served as a vital platform for deepening intercollegiate collaboration. Through multidimensional interactions, we established collaborative connections with multiple university teams.
In addition, our team also participated in the 4th Synthetic Biology Innovation Competition. Through these events, we were exposed to numerous cutting-edge designs and subsequently established connections with several participants, who provided professional advice that enriched our project.
Returning to our experimental exploration, our team selected Lactobacillus casei the chassis strain and designed a systematic genetic engineering modification based on clinical requirements to establish a technical framework characterized by "precise response, functional synergy, and safety controllability." Through dedicated efforts, we successfully accomplished this construction.
Environmental Adaptability of Lactobacillus casei
Testing in LB medium with varying concentrations of bile salts confirmed that the chassis cells maintain normal growth capabilities under simulated intestinal environmental conditions.
Constitutive expression of accA
To enhance the production of short-chain fatty acids \(SCFAs\) in engineered bacteria and thereby provide precursors for oleic acid synthesis, we constructed the plasmid posd-accA/AmpR and introduced it into the host strain via heat shock transformation. Experimental results confirmed that the expression of accA effectively increased SCFA synthesis.
Functional validation of the bile salt-responsive promoter
By constructing a pNZ8048-derived plasmid and transforming it into the engineered strain, we confirmed that 0.1% bile salts could specifically activate the P16090 promoter-driven GFP expression, inducing a significant fluorescent signal.
Expression of OLE1 and oleic acid synthesis
By constructing the P16090-OLE1/KanR plasmid and transforming it into the engineered strain, we confirmed that bile salts could induce the expression of OLE1, and the engineered strain effectively enhanced the production of both oleic acid and short-chain fatty acids.
Expression of defensin
By constructing a P16090-OLE1/KanR plasmid incorporating the self-cleaving 2A peptide sequence \(2A\) and the DEFB4A gene, we successfully achieved co-expression of OLE1 and the defensin within the same operon in the engineered strain. The successful transformation was verified by electrophoresis.
Intestinal environment-adapted biosafety system
To enhance the biosafety of the engineered strain, we successfully constructed a plasmid containing the Holin/Sok toxin-antitoxin system regulated by the P16090 promoter. This system can activate a cell suicide mechanism when the bacteria are outside the intestinal environment, and the successful transformation was verified by electrophoresis.
Responsibility Phase
During the responsibility stage, our team carried out a four-dimensional action of "research - education - charity - collaboration" to deepen the social value of the project. They conducted research on the lack of public knowledge about intestinal health, designed stratified educational plans; carried out public welfare activities for disadvantaged groups to promote health equity; and established a multi-party collaboration network to ensure the sustainable development of the project.
Education and Collaboration
Our LZU-MEDICINE-CHINA team maintains a mindset of profound reflection at every stage of our project: Are we truly fulfilling our responsibility to the world and generating positive impact? Have we achieved our initial objectives? This unwavering commitment to self-inquiry has driven us to create meaningful change in the world. Building on this foundation, we have designed a tiered educational outreach initiative precisely targeting four core groups—from foundational education units \(schools\) and grassroots community/city settings, to national strategic levels, and extending to a global perspective—advancing layer by layer to ensure the light of science reaches every corner that needs it.
Elementary Students Education
In the field of synthetic biology, the integrated approach of humanities practice emphasizes the close connection between scientific education and community participation. In our promotional activities, especially in the lectures for primary schools, we have implemented this concept, converting complex scientific concepts into attractive and easy-to-understand experiences for young learners. Through conducting interactive activities, such as teaching experimental skills and carrying out creative projects like drawing bacteria, our iDEC team has created an environment for primary school students to explore the fascinating world of synthetic biology. These interactions not only stimulated children's curiosity but also laid the foundation for their understanding of health-related issues \(such as post\-surgery rehabilitation\) through interesting practical activities. We believe that this educational promotion can cultivate future scientists and promote a deeper understanding of biological science. Ultimately, these efforts contribute to achieving the broader goals of the iDEC competition, which is to advocate for science dissemination and strive to make synthetic biology accessible and exciting for everyone \(regardless of their background\). This comprehensive approach ensures that science not only continues to develop in the laboratory but also resonates in the community, inspiring the younger generation to participate and contribute to scientific exploration.
University Students Education
Some of our recent initiatives, such as the bio-art competition and interactive workshops, reflect the current trend of academic cross-disciplinary integration, combining scientific knowledge with creative expression. For instance, we encourage students to explore how synthetic biology can innovatively provide affordable medical solutions. Similarly, the artistic works displayed on microscope slides perfectly combine creativity with biology, deepening the audience's understanding of the gut microbiota and making complex scientific concepts more accessible to the public. Through such activities, we actively engage with the community, inspiring participants to think about how they can contribute to the future of biomedicine. This approach not only raises awareness of the applications of synthetic biology but also nurtures the sense of responsibility among young scientists, motivating them to use their knowledge to contribute to the improvement of society and the enhancement of public health. By promoting cooperation and communication among researchers, students, and the broader community, we are opening up innovative solutions to pressing health challenges and cultivating a new generation of citizens with scientific literacy.
Communities and Cities
We have carried out popularization activities on synthetic biology and health knowledge in multiple communities and in many cities across the province, and have received a favorable response.
The Nation
We carried out teaching assistance activities in many places across the country. We also conducted a national survey and conducted street interviews. Based on the results of the survey and the street interviews, we drafted a popular science article about our project and promoted it nationwide through social media.
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Globe
We have produced promotional brochures in multiple languages and a handbook advocating for educational equity, along with bilingual \(Chinese and English\) explanatory articles, hoping to have an impact beyond national boundaries.
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Inclusivity
Our inclusive work aims to disseminate knowledge about intestinal health and synthetic biology, and ensure that people have equal access to medical resources. Through innovative educational and practical activities, we aim to narrow the health literacy gap between urban and rural areas, among low-income groups, disadvantaged groups, and ethnic minority regions, and provide the "Gansu experience" for building a more inclusive and healthy society.
Sustainability
Our project holds significant implications for human sustainable development, with its contributions spanning multiple dimensions including health, economy, society, technology, and the environment.
Beyond improving postoperative recovery conditions and durations, as well as reducing the risks of complications, this project has the potential to drive industrial upgrading, advance healthcare equity, support environmental protection, and foster talent development—all while alleviating the burden on healthcare systems.
Through continuous innovation and practice, our project is poised to make meaningful contributions to achieving the global Sustainable Development Goals.
Entrepreneurship
By visiting advanced enterprises in this field and having conversations with entrepreneurs such as Liu from Jinghong Health, we gained a deep understanding of the industry's operation status. Based on the preliminary research and feedback from practical experiences, our team has completed the formulation of a detailed business plan. In the future, if there is an opportunity, we will strive to implement our project and create a greater impact.
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Conclusions
As of October 2025, our iDEC journey has achieved significant milestones. On a technical level, we have successfully constructed engineered probiotics with "targeted response + multifunctional synergy." In terms of practice, we have carried out educational and public welfare activities to enhance public awareness of gut health and promote health equity. In terms of collaboration, we established a "industry-academia-research-healthcare" network, collaborating with over 10 universities, 3 hospitals, and 1 enterprise to create a sustainable development ecosystem. Our unwavering dedication and collaborative efforts have enabled us to reach key milestones, demonstrating the success of our human practices.
These achievements wouldn't have been possible without the support of Lanzhou University \(research platforms, funding, international resources\), the guidance of clinical experts \(clinical needs alignment, data support\), the assistance of enterprises \(technical and market experience\), the contributions of volunteers \(public welfare activities\), and public participation \(surveys and feedback\). Our team extends sincere gratitude to all.
Reflecting on the project journey, we deeply realize that the value of synthetic biology technology lies not only in laboratory breakthroughs but also in addressing real-world societal issues. The responsibility of researchers is not only to advance knowledge but also to serve the public with science. Through "technology development + education dissemination + collaborative synergy + inclusive practice + commercial transformation," this project provides an innovative solution for perioperative gut health management and contributes to reducing healthcare resource disparities and promoting health equity.
In the future, the team will continue to deepen technology development, expand educational and public welfare coverage, and advance commercial transformation. We are committed to ensuring that the "Gut Health Guardians" project benefits more patients, illuminating every corner with scientific knowledge, and changing more lives through synthetic biology. We aim to contribute more wisdom and strength to the "Healthy China 2030" strategy and the United Nations Sustainable Development Goals.