DREAM INNOVATION GRANT
Dr. Mara Serbanescu BACKGROUND MD: Emory University Anesthesiology Residency: Johns Hopkins University Adult Critical Care Fellowship: Johns Hopkins University
PILOT STUDY
“The Role of Gut Microbial Factors in Delirium in Critically Ill Older Adults” Dr. Mara Serbanescu is an intensivist, anesthesiologist and early-stage physician-scientist whose research focuses on how the gut microbiome influences the development of complications such as organ failure, secondary infections, and cognitive dysfunction in critically ill and postoperative patients. Her work uses systems-level approaches to integrate microbial genome community profiling, metabolomics and immune function data with clinical outcomes to uncover mechanisms that modulate recovery. Advances in culture-independent sequencing have revolutionized our understanding of the gut microbiota, revealing its critical role in regulating immune and metabolic processes. During the perioperative period or acute critical illness, disturbances in the gut microbiota—including the loss of beneficial microbes and expansion of pathogens—are common due to inflammation, antibiotics and other interventions. Preclinical studies suggest that these microbial disruptions influence systemic immunity and neuroinflammation, with microbiota-targeted therapies showing promise in preventing complications such as sepsis and delirium. Serbanescu’s work aims to bridge the gap between these findings and clinical practice by identifying specific microbial features and mechanisms responsible for adverse outcomes. With funding from the International Anesthesia Research Society Mentored Research Award and the Duke PhysicianScientist “Strong Start” award, she is specifically focusing on how derangements in the gut microbiota in critically ill patients shape the types of microbial DNA components that enter the blood in the setting of gut barrier hyperpermeability, as well as the downstream consequences of these gut and blood microbial signatures on immune cell activation and markers of inflammation.
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| DUKE ANESTHESIOLOGY
Now, with support from Duke Anesthesiology’s Dream Innovation Grant, Serbanescu is expanding her scope to investigate the role of the gut microbiome in ICU delirium in older adults – a condition that affects 50% of this population and is associated with long-term cognitive impairment and neurodegenerative diseases. Despite its prevalence, the underlying mechanisms of ICU delirium remain poorly understood, hindering the development of effective treatments. For the pilot study, Serbanescu is collaborating with Dr. Michael Devinney (Duke Anesthesiology) and his clinical research team (the CIPHER Lab), as well as Dr. Jason Arnold (Duke Molecular Genetics and Microbiology), Dr. James Bain (Duke Medicine) and Mary Cooter Wright, MS (Duke Anesthesiology biostatistician). The investigators will use state-of-the-art metabolomics and long-read 16S rRNA sequencing to characterize microbial factors leveraging samples (blood, cerebrospinal fluid and rectal swabs), delirium assessments and clinical data collected from Devinney’s study of older critically ill adults, “Complement Activation in Delirium and Subsequent Cognitive Impairment and Alzheimer’s Disease” (CASCADE-ICU). By analyzing samples from multiple body sites, the study aims to provide a holistic understanding of gut-brain interactions in critical illness and ICU delirium. The findings from Serbanescu’s study have the potential to revolutionize our understanding of ICU delirium by revealing a novel role of the gut microbiota in its development. Additionally, the study will provide foundational data for future research into the gut-brain axis and its implications for neurodegenerative diseases like Alzheimer’s. Long-term, this research could pave the way for microbiota-targeted therapies to prevent or treat delirium, ultimately improving outcomes for critically ill older adults.