Lung transplantation is an important treatment of end-stage lung disease; however, post-surgical complications, especially allograft rejection (AR) and pulmonary infection (PI), remain a major challenge for patients. These complications not only affect patient survival, but also reduce the success rate of surgery. To address this issue, we need to gain a deeper understanding of the organism-related biological processes in lung transplant patients after surgery.

On September 1, 2023, a research team consisting of several distinguished scientists, including Prof. Chen Chang from Shanghai Pulmonary Hospital of Tongji University, Prof. Fang Wenjie and Prof. Pan Weihua from Naval Military Medical University, published online in Signal Transduction and Targeted Therapy (IF=39), a top international journal, a paper entitled "Intestinal microbiota links to allograft stability after lung transplantation: a prospective cohort study". The significance of this study lies in the fact that it is the first international multicenter study to reveal the link between intestinal microbiota and allograft stability after lung transplantation, as well as providing new targets and directions for lung transplantation research and treatment in the future.

The research team established a prospective cohort covering 85 lung transplant recipients (LTRs) from four different lung transplant centers. Postoperative paired stool and serum specimens from these lung transplant recipients were further collected and the samples were categorized into AR, PI, and event-free (EF) groups based on the diagnosis at the time of sampling. The fecal samples were analyzed by macro-genomic sequencing, and the results showed that the gut microbiome of AR exhibited a significant reduction in species and diversity. Meanwhile, further testing analysis for serum specimens and clinical information revealed reduced serum metabolites and increased inflammatory cytokines in AR and PI. Notably, the reduction of Bacteroides uniformis in AR was significantly and negatively correlated with serum IL-1β and IL-12, which provides a new mechanistic explanation for the influence of gut microbial communities on graft stability after lung transplantation. In addition, this study further combined microbiome, metabolome and clinical parameters to construct machine learning models capable of efficiently predicting AR (AUPRC = 0.801) and PI (AUPRC = 0.855), with the microbiome dataset showing particularly high diagnostic discriminatory power. In conclusion, a disruptive gut microbiota was significantly associated with allograft rejection and infection as well as systemic cytokines and metabolites after lung transplantation.

Research flow diagram of this study

The significance of this study lies not only in revealing a profound link between gut microbiota and lung transplantation stability, but also in providing an important direction for future research and pointing the way to further mechanistic experiments thereafter. Understanding the role of the gut microbiota may help predict and prevent the development of serious complications such as AR and PI, and improve the survival and quality of life of patients after lung transplantation.

The corresponding author of this study is Prof. Chen Chang of Shanghai Pulmonary Hospital, Tongji University, and the co-corresponding authors include Profs. Fang Wenjie and Pan Weihua of Naval Military Medical University. This cross-institutional collaboration provides rich professional knowledge and resources to support this study, and together they are advancing cutting-edge research in the field of lung transplantation.

CV of Prof. Chen Chang

Chen Chang is a Professor and Doctoral Supervisor at the School of Medicine, Tongji University, and Secretary of the Party Committee and Chief Physician at the Shanghai Pulmonary Hospital affiliated with Tongji University. As the director and head of several major platforms, including the Clinical Research Center of Thoracic Surgery of Tongji University, Shanghai "Top Priority" Respiratory Disease Center and Shanghai Lung Transplantation Engineering and Technology Research Center, Prof. Chen Chang has led a number of domestic and international multi-center clinical and basic research in the field of thoracic surgery, and the translational results have reached the international advanced level.

He has undertaken one project of the National Key Research and Development Program of the 14th Five-Year Plan, one project of the Artificial Intelligence Innovation Tasks of the Ministry of Industry and Information Technology, one project of the National Blockchain Innovation and Application Project, one project of the National Natural Science Foundation of China (NSFC)'s Major Research Program, one project of the Cultivation Program, and two projects of the Face-level Program. He is also the author of 1 major research program, 1 cultivation program, and 2 top-level programs of NSF. He has published 194 SCI papers as corresponding and co-corresponding author, with a cumulative impact factor of 1447.4, including J Clin Oncol, Signal Transduct Target Ther, Science Transl Med, Mol Cancer, Eur Respir J, Radiology, J Thorac Oncol, Adv Funct Mater, JAMA Surg, JAMA Netw Open, and so on. He has obtained 58 patents for his inventions. He has been honored with the Second Prize of Science and Technology Progress of the Ministry of Education, the First Prize of Shanghai Anti-Cancer Science and Technology Award, the Second Prize of Shanghai Medical Science and Technology Award, and other scientific and technological awards. He has been awarded the honorary titles of State Council Special Allowance, National Project of One Million Talents, National Young and Middle-aged Experts with Outstanding Contributions to Health, Shanghai Medical Artisan, Shanghai Leading Talents, Shanghai Outstanding Discipline Leader, and so on.

Introduction to Shanghai Lung Transplantation Engineering and Technology Research Center

Shanghai Lung Transplantation Engineering and Technology Research Center (hereinafter referred to as "the Center") is the largest multidisciplinary platform for lung transplantation-related scientific research and clinical translation in Shanghai. Relying on the disciplinary advantages of Shanghai Pulmonary Hospital affiliated to Tongji University in transplantation, immunology and tissue engineering, the Center has been focusing on lung transplantation technological innovation, preservation and functional repair of transplanted lungs, remodeling of the immune microenvironment after lung transplantation and immunotherapy, as well as stem cell exocytosis and regenerative medicine, bio-tissue engineering and other frontier areas, and has successively made efforts to innovate lung transplantation surgical techniques, reduce ischemia/reperfusion injury of grafts, promote immune tolerance after lung transplantation, and so on. The center has achieved breakthroughs in both scientific research and clinical translation on key issues such as innovative lung transplantation surgical techniques, reduction of ischemia/reperfusion injury in grafts, and promotion of immune tolerance after lung transplantation.

The Shanghai Pulmonary Hospital, which is one of the earliest hospitals to carry out lung transplantation in China, has been the first to carry out the first lung transplantation in 2003, and has successively set up a number of domestic and international firsts, such as the first re-lung transplantation in Asia and the first living lung lobe transplantation in China. Relying on the Department of Thoracic Surgery of Shanghai Pulmonary Hospital and integrating the advantageous resources of key disciplines such as Respiratory Critical Care, Anesthesiology, Pulmonary Circulation, etc., the Center has set up a multidisciplinary team of lung transplantation specialists and full-time team, and set up an exclusive lung transplantation ward and an intensive care ward. 2020, the Center was approved to establish the "Shanghai Lung Transplantation Engineering Technology Research Center", which is capable of carrying out single-lung transplantation. In 2020, the center will be approved as "Shanghai Lung Transplantation Engineering and Technology Research Center", which is capable of carrying out all kinds of lung transplantation surgeries such as single-lung transplantation, sequential transplantation of two lungs, lobe transplantation of living lungs, re-transplantation of lungs and simultaneous lung transplantation combined with bilaterally lung volume reduction. The center is the first in China to realize inter-hospital transfer of lung transplant recipients by ECMO, inter-provincial transport of lungs by helicopter and air, and the first EVLP in China to be applied to the repair and monitoring of marginal donors, thus guaranteeing the successful implementation of salvage lung transplantation for patients with acute and critical illnesses. The volume of lung transplants performed by the Center now ranks first in Shanghai and fourth in China, with a survival rate higher than the national average and close to the international advanced level.