James Davison, PhD
The American Society of Parenteral and Enteral Nutrition (ASPEN) Rhoads Research Foundation has awarded Duke Anesthesiology’s James Davison, PhD, a lab research analyst and director of The Wischmeyer Lab, a $25,000 grant (with potential second-year funding of an additional $25,000) for his project, titled “Modulation of Organ Injury by Faecalibacterium Prausnitzii in Critical Illness.” Dr. Davison’s long-term research objective is to establish nutritional and probiotic therapies that support organ function and improve outcomes in critical care patients.
According to the project’s abstract, intensive care unit (ICU) admission is associated with a loss of “health promoting” bacteria and a rapid dysbiosis of the intestinal microbiota. Specifically, a recent multi-center ICU microbiome clinical trial from The Wischmeyer and Knight (UC San Diego) Labs demonstrated a significant loss of the probiotic microorganism, Faecalibacterium prausnitzii, which generates metabolites and anti-inflammatory peptides that support intestinal function and attenuate local inflammation in experimental colitis models. Based on the clinical findings and the known roles of F. prausnitzii in attenuating local inflammation, Dr. Davison and his project mentor, Dr. Paul Wischmeyer, have developed this central hypothesis: F. prausnitzii and/or its metabolites attenuate systemic inflammation, improve organ function and reduce morbidity/mortality in sepsis. Thus, their two project aims include 1) directly addressing the working hypothesis that oral supplementation of F. prausnitzii protects intestinal and extra-intestinal organ function during sepsis. Using the accepted cecal-ligation and puncture model of sepsis, they will test if F. prausnitzii attenuates systemic inflammation and promotes extra-intestinal organ function. They will also utilize next-generation sequencing to determine if F. prausnitzii mediates metabolic and inflammatory transcriptional responses of organs in septic mice, and 2) directly addressing the working hypothesis that peptides and metabolites derived from F. prausnitzii suppress systemic inflammation. Using protein and metabolite mass spectrometry, they will test for enrichment of serum metabolites and peptides that are only present in mice that receive F. prausnitzii. They will synthesize peptides that are unique in the serum of mice that receive F. prausnitzii and will test if oral gavage or tail-vain injection of these synthesized peptides have the capacity to reduce inflammation in septic mice.
Drs. Davison and Wischmeyer believe that this project addresses a significant obstacle that prevents wider use of probiotic therapies (and other nutritional therapies) in critical illness – and that the lack of understanding of the molecular mechanisms mediate probiotic contributions to human health. They predict that their translational research plan will support their long-term research objectives in identifying novel mechanisms that mediate probiotic organ protection in illness, leading to new therapies to prevent and treat sepsis and critical illness.