How do Vampires Suck Blood?

Abstract Lampreys are blood-sucking vampires in the marine. From a survival perspective, it is expected that lamprey buccal gland exhibits a repository of pharmacologically active components to modulate the host’s homeostasis, inflammatory and immune responses. Several proteins have been found to function as anticoagulants, ion channel blockers, and immune suppressors in lampreys, while small metabolites have never been explored in detail. In this study, by analyzing the metabolic profiles of 14 different lamprey tissues, we have identified two groups of blood-sucking-associated metabolites, i.e., kynurenine pathway metabolites and prostaglandins, in the buccal gland and they can be injected into the host fish to ensure a steady and sustained blood flow to the feeding site. These findings demonstrate the complex nature of lamprey buccal gland and highlight the diversity in the mechanisms utilized for blood-sucking in lampreys. In addition, a lamprey spatial metabolomics database ( https://www.lampreydb.com ) was constructed to assist studies using lampreys as model animal. The database contains detailed qualitative, quantitative, and spatial distribution information of each detected metabolite, and users can easily query and check their metabolites of interest, and/or identify unknown peaks using the database. Significance Statement Lampreys are one of the two surviving jawless vertebrate groups that hold the key to our understanding of the early vertebrate evolution, adaptive immune origin, and developmental neurobiology. Here, we applied a spatial metabolomics approach to study the lamprey-host interaction. Two groups of metabolites, i.e., kynurenine pathway metabolites and prostaglandins, were found in the lamprey buccal gland, which modulate the host’s homeostasis, inflammatory and immune responses. The establishment of the first tissue-wide spatial lamprey metabolomics database in this study facilitate future studies in biochemistry, clinical chemistry, natural product discovery, medicine, and metabolomics using lampreys as a model animal.