The National Institutes of Health’s (NIH) National Institute of General Medical Sciences has awarded Duke Anesthesiology’s Mara Serbanescu, MD, a five-year, $2,018,750 Maximizing Investigators’ Research Award (MIRA) for her project, “Unraveling Effects of Gut and Blood Microbial Signatures on Immune Phenotypes and Organ Dysfunction in Sepsis.”
Sepsis remains a leading cause of death in the ICU, yet therapies targeting the immune dysregulation that drives its morbidity and mortality are still lacking. While preclinical studies point to the gut microbiome as a key modulator of immune function, the translation of microbiome-targeted therapies into clinical care has been hampered by limited data on host-microbe interactions in septic patients.
Serbanescu’s research addresses this critical gap by investigating how the composition of the gut microbiota—and translocation of immuno-active microbial products into the bloodstream—shapes immune responses and organ injury in critically ill patients. Her team will apply highly sensitive sequencing approaches to detect the “genetic fingerprints” of bacteria in the blood, aiming to better define the phenomenon of microbial translocation in sepsis. She hypothesizes that many of these microbial signatures originate from the gut, and that different gut-derived bacterial products interact with immune cell receptors to produce species-specific—and sometimes opposing—immune effects. In this way, the composition of the gut microbiota may influence the intensity of immune activation or exhaustion as well as end-organ injury and susceptibility to secondary infections during ICU stay.
Using a prospective longitudinal ICU cohort, her study will integrate gut microbiota profiling, blood microbial DNA analysis, immune phenotyping, and clinical outcomes. It also incorporates measures of intestinal permeability and metabolomics to better understand how gut barrier integrity influences translocation and immune dysregulation. Finally, ex vivo immune assays will assess how patient-derived microbial DNA signatures influence TLR-mediated signaling and cytokine production.
This MIRA marks Serbanescu’s first NIH award and a major milestone in her career as a physician-scientist. She will carry out this work in collaboration with Dr. Jason Arnold (Duke Molecular Genetics and Microbiology) and Mary Wright, MS (Duke Anesthesiology), along with ongoing mentorship and scientific input from Drs. Paul Wischmeyer (Duke Anesthesiology), Jamie Privratsky (Duke Anesthesiology), Smita Nair (Duke Surgery), and Neil Surana (Duke Pediatrics).
“The findings from this study will enhance our understanding of how the gut microbiota shape host responses in sepsis and may reveal new therapeutic strategies for this lethal disease,” says Serbanescu, assistant professor of anesthesiology. “By identifying how specific gut bacteria influence immune responses and meaningful outcomes like organ dysfunction and secondary infection, we hope to uncover both harmful and protective microbial signatures that could serve as future targets for personalized therapies.”