2023 IARS Mentored Research Award Recipient Interview: Mara A. Serbanescu, MD

Fiber as Foe? Impact of Fiber-Containing Enteral Nutrition on Gut and Oral Microbial Community Dynamics in Critically Ill Trauma Patients: A Pilot-Randomized Trial

Abstract Presentation:

Oral Abstract Session: Critical Care Abstracts, Friday, May 17, 6:09 pm – 6:17 pm, Quinault, Hyatt Regency Seattle

The study of the microbiome first piqued Dr. Mara A. Serbanescu’s interest during anesthesiology residency at Johns Hopkins. Although her mentor Dr. Cyrus Mintz was primarily focused on anesthetic neurotoxicity at the time, an opportunity became available to conduct a pilot study to investigate the effect of anesthetics on the gut microbiome in a mouse model and Dr. Serbanescu jumped at the opportunity to be involved. Over the next 5 years, her fascination with this topic only grew as the pilot study evolved into a new area of focus in Dr. Mintz’s lab. As her knowledge advanced on this important topic, Dr. Serbanescu recognized that translating microbiome research would offer profound implications for patients, both by reducing complications from surgery and for those battling critical illness. Now, as an assistant professor of Anesthesiology in the Division of Critical Care at Duke University, Dr. Serbanescu continues to make major strides in uncovering vital answers to this area of study. In 2023, she was acknowledged with an IARS Mentored Research Award for her research focused on identifying how dietary interventions provided in the ICU affect the community of microbes residing in our gastrointestinal (GI) tract (the gut microbiota) and has begun enrolling patients. During an Oral Abstract Session on Friday, May 17 at the 2024 Annual Meeting, presented by IARS and SOCCA, Dr. Serbanescu will present results from an offshoot of her research, a pilot randomized control trial that assessed the effects of enteral nutrition (EN) containing prebiotic short-chain fructooligosaccharides (scFOS) versus fiber-free EN on gut and oral microbial composition in patients admitted to the ICU with severe trauma. Below, Dr. Serbanescu shares her fascination with the study of the microbiome, the evolution of her research and how the IMRA will impact her career and research.

1. For this research, you are…

I’ve served as a clinical investigator on this study. The project was conducted by my mentor, Dr. Paul Wischmeyer, who is the principal investigator. The enrollment phase ended just before I transitioned to faculty at Duke in 2022, and after that, I took the lead on the sequencing, analysis and interpretation phases.

2. What drew you to this area of research? Has it evolved since your initial research project?

I first became interested in studying the microbiome during anesthesiology residency at Johns Hopkins. My mentor there, Dr. Cyrus Mintz, was primarily focused on anesthetic neurotoxicity but had an opportunity to conduct a pilot study to investigate the effect of anesthetics on the gut microbiome in a mouse model. He knew my interest was in investigating host responses in sepsis and offered me the chance to work with him on this pilot study. He emphasized the emerging literature on microbiota-immune crosstalk, and the potential for me to explore the significance of these interactions in the perioperative period in future work. Truly so much of my current success is due to his foresight and enduring guidance over the following 5 years as we turned the pilot study into a new area of focus in his lab. Over that time, we used mouse models to learn more about how interventions like 100% oxygen and anesthetics affect the microbiota, and the implications of these changes on immune responses. Meanwhile, my clinical practice evolved to include specialization in adult critical care medicine, which I continued while on a T32 at Johns Hopkins. With that, I became increasingly aware of how translating our microbiome research to patients could have profound implications – both on our understanding of immune responses elicited by surgery and critical illness, and in possible treatment options that could be developed as a result. I decided to work towards an independent research career with this translational/clinical focus. In 2022, I was offered a great opportunity to pursue this path at Duke University, with guidance from Dr. Wischmeyer, an expert in the field of clinical nutrition and gut microbiome therapeutics, and others from the Duke Microbiome Center, which is a truly unique institutional resource. The study I’ll be presenting at IARS is the first product of my work in patients. It highlights how unique changes in the microbiota in critically ill patients (which are a product of the ecologic pressures faced in the ICU) may significantly alter how microbiome-targeted therapies work in this population. Our findings truly exemplify what drew me to clinical research, underscoring how much we have left to learn about the gut microbiota in critically ill and postoperative patients, and the potential clinical impact of better understanding this “forgotten organ.”

3. What are the goals you most want to accomplish in your work with this research project?

The big picture goal for both this study and my IARS Mentored Research Award project is to identify how dietary interventions provided in the ICU affect the community of microbes residing in our GI tract (the gut microbiota). We know that the composition of the gut microbiota is profoundly altered in ICU patients, and that certain changes – like increased occupation of potential pathogens (like E. Coli, Klebsiella, and Enterococcus) – have repeatedly been associated with a greater risk of secondary infection and death in this population. There’s still a lot we don’t know though, like how the gut microbiota influence immune cell responses, which will be one area of focus of my IMRA project. We also don’t know how prebiotics and other microbiota-targeted therapies affect microbial responses when these interventions are provided in the setting of severe ICU-associated dysbiosis.

The latter question is addressed in the study I’ll be presenting at IARS. This project was a pilot randomized control trial that assessed the effects of EN containing prebiotic short-chain scFOS versus fiber-free EN on gut and oral microbial composition in patients admitted to the ICU with severe trauma. We investigated not only how these different nutritional formulations affect the abundance (i.e. relative amounts) of individual microbes over a 10-day study period, but also how they affect interactions between microbes, like cross-feeding and competition. These community interactions are crucial to understanding microbial responses to any dietary intervention but have never been directly investigated in an ICU microbiome study.

4. What is the potential impact of your research on the field of anesthesia and patient care?

Our research aims to shed light on the effects of different dietary interventions on the gut microbiota of ICU patients and the impact of these gut microbial changes on immune responses. By better understanding these intricate relationships, we hope to provide valuable insights that could inform clinical practice in several ways.

Firstly, understanding how specific nutritional formulations influence the microbiota will enable clinicians to better tailor dietary interventions to promote a healthier gut microbiota, which may improve outcomes in critically ill patients. For example, scFOS prebiotic-supplemented formulas are readily available in the ICU and hypothesized to help support beneficial microbes. However, our pilot study suggests that when they are initiated after several days of antibiotics and no other EN, they may actually worsen dysbiosis. We found that in the setting of these ecologic pressures, scFOS-EN favored the growth of more resilient colonizers, including potentially pathogenic microbes (pathobionts) like E. coli and Klebsiella that outcompete other beneficial commensals for this nutrition. Growth of these pathobionts is associated with worse outcomes and was really what we had hoped to prevent with the scFOS-EN intervention. Our findings highlight that responses to prebiotic scFOS in critically ill patients are quite different than those reported in other conditions and underscores the need to consider the importance of timing and context in microbial responses to nutritional interventions.

In the IMRA project, we will delve deeper into the consequences of these gut microbial community dynamics. The project is a substudy of a Department of Defense-funded randomized control trial (SendHome). The parent study, led by Dr. Paul Wischmeyer and Dr. Krista Haines, an assistant professor in the Department of Surgery, explores effects of a targeted nutrition regimen that includes early parenteral nutrition (PN) versus standard care on clinical outcomes in patients admitted to the ICU following trauma laparotomy. In the sub-study, we’ll use culture-intendent sequencing techniques to identify effects of these interventions on both gut microbial composition, and translocation of microbial products into the circulation, and hope to delineate how PN affects the gut microbiota in this pragmatic setting. Ultimately, our findings have the potential to redefine the concept of translocation and optimize the use of PN in the ICU, leading to improved patient outcomes and enhanced clinical care.

5. What are the benefits of presenting your research at the IARS Annual Meeting?

This will be my fifth year attending the IARS Annual Meeting, and I’ve had the privilege of presenting my work from animal studies in previous years. These presentations have been incredibly important to me, and serve as milestones that trace my progression and growth as a clinician-scientist. The IARS meeting is a great platform, allowing clinicians and scientists with diverse viewpoints and expertise to share insights and exchange ideas, all aimed at improving the way we care for patients. Presenting to such a receptive and knowledgeable audience is incredibly valuable. In the past, the feedback and interactions at this meeting have both shaped how I think about my work and led to new connections and opportunities for collaboration. I’m really looking forward to what this year’s meeting will bring!

6. How will the 2023 IMRA affect your research and professional trajectory?

Receiving the IMRA is a tremendous honor, and I am so grateful to the committee for choosing to invest in my career growth. On a personal level, receiving the IMRA was a significant milestone. It is the first significant source of funding supporting my work and allows me the ability to continue my training in microbiome and clinical sciences. As an early-stage clinician-scientist progressing towards research independence, this affirmation and support are truly invaluable. The award is also a great validation of the importance and potential impact of microbiome research in the field of anesthesiology and critical care medicine. For one, I hope this recognition helps broaden interest and excitement for microbiome-oriented research. But even more than that, this support from IARS truly speaks to how diverse our research focus and impact can be as anesthesiologists. My hope is that this motivates other emerging physician-scientists to be creative and open-minded in their research questions (including ones that are microbiome-related, there’s plenty of room in this space!).

7. How is your current research project influenced by your initial 2023 IMRA research project?

The current study focuses on microbial responses to prebiotic-supplemented EN and actually precedes the IMRA. The study period for my IMRA award began earlier this spring, and we have just started enrolling patients – more to come next year! 

8. Is there anyone else you wish to acknowledge as part of this research team?

So many remarkable people have helped me bring this work forward and I would love to show my appreciation for their efforts. I want to again acknowledge my mentors Dr. Wischmeyer and Dr. Mintz – so much of my growth and success is a product of their guidance over the past years. I’m also incredibly grateful to leadership in the Duke Department of Anesthesiology including Dr. Joseph Mathew (Department Chair), Dr. Miriam Treggiari (Vice Chair of Research), and Dr. Vijay Krishnamoorthy (Division Chief of Critical Care) for providing me with the time and resources to progress towards my research and career goals. Biostatistician, Mary Cooter Wright, and Assistant Director of the Duke Microbiome Center, Jason Arnold, have been immensely helpful in both completing the current project and crafting the IMRA proposal and I greatly appreciate their time and support. I’m thankful to Dr. James Wright of Resphera Biosciences who tirelessly taught me to use microbiome bioinformatics pipelines using R-based programming, allowing me to perform the analysis on the current study. I’m also grateful for our Anesthesiology Clinical Research Unit for helping with enrollment and sample collection. The current project was funded through an investigator-initiated award by Abbott Pharmaceuticals, and we greatly value their support.

As we have also discussed the IMRA, I also want to express my deepest gratitude to the IARS Committee for their support and Tricia Brazil for all her help with the award. Dr. Krista Haines has been an incredible collaborator and teacher, helping me maneuver in this new clinical research space. Additional huge thank yous go to Shauna Howell and Dana Giangiacomo in the Department of Surgery, and my grants manager Carrie Holbert who have all been instrumental in getting the IMRA project off the ground.

9. Outside of your research, what might someone be surprised to learn about you?

I majored in comparative literature and reading is still one of my favorite activities, though I feel slightly guilty that I’ve now resorted completely to e-books (only way to fit it in).