Recently, Professor Hu Bei's team from Guangdong Provincial People's Hospital made significant progress in the field of sepsis research. Their research, titled "Dietary tryptophan supplementation prevents sepsis by enhancing macrophage bacterial defense through GPR37 activation", was published in the international authoritative journal Chinese Medical Journal on June 8, 2026. The study discovered that dietary tryptophan (Trp) can prevent sepsis by regulating the intestinal microbiota and its metabolic functions, generating the key metabolic product indole-3-pyruvic acid (IPyA), which then activates the GPR37 receptor on the surface of macrophages, enhancing the bacterial phagocytic ability of macrophages, and ultimately effectively preventing sepsis. This provides a new nutritional intervention strategy and molecular target for the prevention and treatment of sepsis.
Research Background and Core Findings
Sepsis is a life-threatening disease and one of the main causes of death among hospitalized patients. There are approximately 50 million cases worldwide each year. Currently, in addition to conventional hormone and antibiotic treatments, effectively regulating the host's immune system is crucial for controlling sepsis-related infections. Macrophages, as a key cell type of the host's immune system, play a critical role in resisting infections through their phagocytic and bactericidal functions are of great significance in resisting infections, but during sepsis, the functions of macrophages are easily damaged, and there is a metabolic disorder in the plasma, with a reduction in protective metabolites and an increase in toxic metabolites. New anti-infection strategies needed to be explored urgently.
Based on this, the research team obtained several key findings through animal experiments, cell experiments, and clinical sample analysis: Dietary tryptophan supplementation can significantly increase the survival rate of septic mice, alleviate multi-organ damage such as in the lungs, liver, and kidneys, reduce plasma levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and inflammatory factors (IL-6, IL-1β, TNF-α), and this protective effect depends on the intestinal microbiota. When the intestinal microbiota was cleared, the protective effect of dietary tryptophan disappeared, while the feces of mice fed with dietary tryptophan reproduced the protective effect.
It was also found that the average IPyA levels in sepsis patients and septic mouse models were significantly reduced, and the plasma IPyA level of patients was negatively correlated with the AST level; exogenous supplementation of IPyA can simulate the protective effect of dietary tryptophan, prolong the survival time of septic mice, alleviate organ damage, and reduce the bacterial load in blood and peritoneal lavage fluid (PLF). The mechanism is that IPyA can directly bind to GPR37 on the surface of macrophages, activate small GTPase RAC1/CDC42, increase the expression of actin-related protein (Arp) 2/3, and ultimately enhance the phagocytic ability of macrophages against bacteria. It also enhances phagocytosis in patient-derived macrophages.
Research Significance and Outlook
Professor Hu Bei pointed out that this study is the first to clarify the "dietary tryptophan - intestinal microbiota - IPyA - GPR37 - macrophage phagocytosis" regulatory axis in the prevention of sepsis, not only enriching the understanding of the pathogenesis of sepsis, but also providing a new direction for the prevention and treatment of sepsis. On one hand, dietary tryptophan is an essential amino acid for the human body, with widely available sources and high safety, and is expected to become a preventive nutritional supplement for high-risk populations of sepsis (such as patients undergoing major surgeries and those with compromised immune function); on the other hand, IPyA and its receptor GPR37 can be used as drug development targets, laying the foundation for the development of new drugs for sepsis treatment. Currently, the team has begun the screening and optimization of IPyA analogues, and plans to conduct a prospective cohort study on the use of dietary tryptophan for the prevention of sepsis in clinical settings, to further verify its clinical application value. This research has received funding from projects such as the National Natural Science Foundation of China, the National Key Research and Development Program of China, and the Guangdong Provincial Key Research and Development Program.
Reference
Title of original paper: Dietary tryptophan supplementation prevents sepsis by enhancing macrophage bacterial defense through GPR37 activation
Journal: Chinese Medical Journal
DOI: https://doi.org/10.1097/cm9.0000000000004108
About Professor Bei Hu from Guangdong Provincial Hospital of Chinese Medicine, Southern Medical University, China
Prof. Bei Hu is the Chief Physician, Deputy Director (in charge of daily work) and Party Branch Secretary of the Department of Emergency Medicine, Guangdong Provincial Hospital.
He is also a doctoral supervisor. His research focuses on the pathogenesis, prevention, and treatment of sepsis and septic cardiomyopathy. He has led over 10 research projects funded by the National Natural Science Foundation of China and published more than 30 SCI-indexed papers in leading journals, including Intensive Care Medicine , Critical Care , and Journal of Nanobiotechnology .
Funding information
This study was supported by grants from the Natural Science Foundation of Guangdong Province (No. 2022B1515020104), the National Key Research and Development Program Intergovernmental Key Projects (No. 2023YFE0114300), the National Natural Science Foundation of China (Nos. 82072139, 82270253 and 82072225).
Chinese Medical Journal
Experimental study
Animals
Dietary tryptophan supplementation prevents sepsis by enhancing macrophage bacterial defense through GPR37 activation
8-Jun-2026
The authors declare no conflicts of interest