ROLE OF CHANGES IN LIPOPROTEINS, LIPIDOMES, AND GUT MICROBIOTA IN THE PATHOGENESIS OF PERSISTENT INFLAMMATION, IMMUNOSUPPRESSION, AND CATABOLISM SYNDROME: A PROSPECTIVE COHORT STUDY

ABSTRACT: Persistent inflammation, immunosuppression, and catabolism syndrome (PIICS) is a severe condition that occurs in patients in intensive care units (ICUs), and it is associated with high morbidity and mortality. This prospective cohort study investigated the dynamic changes in lipoproteins, lipidomics, and gut microbiota from days 1 to 7 posthospitalization for PIICS to elucidate their roles in the pathophysiology of PIICS. Patients admitted to the ICU were enrolled, and blood and fecal samples were collected 1 day and 7 days after admission. Lipidomic profiles were analyzed using liquid chromatography with tandem mass spectrometry, and gut microbiota composition was assessed using 16S RNA sequencing Patients who subsequently developed PIICS had lower levels of high-density lipoprotein, low-density lipoprotein, and other lipoproteins than those in patients without PIICS. Most of the lipids and gut microbes decreased significant in PIICS-2 compared to PIICS-1. Day 7 high-density lipoprotein levels were predictive of PIICS diagnosis and prognosis, and were correlated with inflammatory marker levels and 30-day survival. These findings suggest an interplay between lipid metabolism and gut microbiota in PIICS development; therefore, microbiota-mediated regulation of lipid metabolism is a potential therapeutic target for PIICS. This study provides novel insights into the complex mechanisms underlying PIICS and highlights the importance of further research into targeted interventions for critically ill patients with this syndrome.