2025 DIG Research Project | "The Role of Gut Microbial Factors in Delirium in Critically Ill Older Adults"
Background
Mara Serbanescu, MD, is an assistant professor in Duke Anesthesiology’s Critical Care Medicine Division and an early-stage clinician-scientist. She practices as an intensivist at Duke University Hospital (DUH Surgical-ICU) and Duke Raleigh Hospital, and as an anesthesiologist in the General, Vascular, and Transplant Anesthesiology Division. Her research focuses on exploring how the communities of microbes residing throughout our bodies (the microbiota) impact host responses and influence the development of complications such as organ failure, secondary infections, and cognitive dysfunction in critically ill and postoperative patients. Long-term, her goal is to uncover modifiable features of the microbiome that can be targeted to improve outcomes in critical illness and after surgery.
Serbanescu grew up in Atlanta, attending college at Emory University where she majored in comparative literature, before continuing at Emory for medical school. In 2016, she moved to Baltimore to complete her anesthesiology residency, critical care fellowship, and post-doctoral research training at Johns Hopkins University. There, under the mentorship of Dr. David Mintz, she embarked on a previously uncharted area of anesthesiology research—exploring how perioperative exposures, such as volatile anesthetics and oxygen, impact the gut microbiome and the downstream consequences of these microbiota changes on immune responses. Her preclinical work resulted in first-author publications, invited presentations at national conferences, including the International Anesthesiology Research Society (IARS) and Shock, and the reception of the Association of University Anesthesiologists’ Junior Faculty Perioperative Medicine Research Award.
Aiming to translate her preclinical findings to patients, Serbanescu arrived at Duke in 2022. With departmental support, including additional post-doctoral training (T32) in bioinformatics and mentorship from Dr. Paul Wischmeyer, she has developed a unique skillset to develop her independent clinical/translational microbiome research program. Her work uses systems-level approaches to integrate microbial genome community profiling, metabolomics, and immune function profiles with clinical data to unravel host-microbiome interactions that may impact recovery. Earlier this year, Serbanescu was awarded the IARS Mentored Research Award to study the impact of a structured nutritional intervention program on gut microbial composition, gut barrier integrity, and gut microbial translocation to the blood. She also received the Duke Physician Strong-Start Award to support her transition to independence and growth of the Anesthesiology Microbial Profiling Lab. To accomplish her research agenda, she collaborates closely with Duke Anesthesiology biostatistician Mary Cooter Wright and is an active member and collaborator in the Duke Microbiome Center.
Research
Serbanescu was selected as the recipient of the 2025 DREAM Innovation Grant, an annual award that supports innovative high-risk and potentially high-reward investigations to accelerate anesthesiology, perioperative, critical care, and pain management research, supported by Duke Anesthesiology’s Duke DREAM Campaign. Serbanescu’s project, “The Role of Gut Microbial Factors in Delirium in Critically Ill Older Adults,” aims to address a critical gap by investigating the potential role of gut microbiota in ICU delirium. Delirium affects more than 50% of older adults in the ICU and leads to increased mortality and long-term cognitive impairment, including Alzheimer's disease (AD) and related dementias. Despite its prevalence, the underlying mechanisms of ICU delirium remain poorly understood, hindering the development of effective treatments. Emerging evidence suggests that the gut microbiota may play a crucial role in brain dysfunction by influencing blood-brain barrier integrity and neuroinflammation, via changes in the metabolic landscape and/or by influencing the entry of certain microbial DNA components (MCs) into the brain. However, these processes have never been studied in the context of critical illness.
Serbanescu’s innovative pilot study aims to investigate the association between ICU delirium and gut microbial factors, including microbial-derived metabolites and microbial DNA components, in blood and cerebrospinal fluid (CSF) of critically ill older adults. Serbanescu is collaborating with a multidisciplinary team of experts including Dr. Michael Devinney (Duke Anesthesiology), Dr. Jason Arnold (Duke Molecular Genetics and Microbiology and assistant director of the Duke Microbiome Center), Dr. James Bain (Duke Medicine and director of the Stedman Metabolomics Laboratory) and Cooter Wright. The investigators will be using state-of-the-art metabolomics and long-read 16S rRNA sequencing to characterize microbial factors leveraging samples (blood, cerebrospinal fluid (CSF), 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).” 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 such as AD. Long-term, her research could pave the way for microbiota-targeted therapies to prevent or treat delirium, ultimately improving outcomes for critically ill older adults