The relationship between tryptophan metabolism and gut microbiota: Interaction mechanism and potential effects in...

Human health is influenced by the gut microbiota, particularly in aspects of host immune homeostasis and intestinal immune response. Tryptophan (Trp) not only acts as a nutrient enhancer but also plays a critical role in the balance between host immune tolerance and gut microbiota maintenance. Both endogenous and bacterial metabolites of Trp, exert significant effects on gut microbial composition, microbial metabolism, the host immunity and the host-microbiome interface. Trp metabolites regulate host immunity by activating aryl hydrocarbon receptor (AhR), thereby contributing to immune homeostasis. Among Trp metabolites, AhR ligands include endogenous metabolites (such as kynurenine), and bacterial metabolites (such as indole and its derivatives). Here, we present a comprehensive analysis of the relationships between Trp metabolism and 14 key microbiota, encompassing fungi (e.g., Candida albicans, Aspergillus), bacteria (e.g., Ruminococcus gnavus, Bacteroides, Prevotella copri, Clostridium difficile, Escherichia coli, lactobacilli, Mycobacterium tuberculosis, Pseudomonas aeruginosa, Staphylococcus aureus, Helicobacter. Pylori), and viruses (e.g., SARS-CoV-2, influenza virus). This review clarifies how the gut microbiota regulates Trp metabolism and uncovers the underlying mechanisms of these interactions. And increased mechanistic insight into how the microbiota modulate the host immune system through Trp metabolism may allow for the identification of innovative therapies that are specifically designed to target Trp absorption, Trp metabolites, the gut microbiota, or interactions between Trp and gut microbiota to treat both intestinal and extra-intestinal inflammation as well as microbial infections.