DFI Multidisciplinary Grant Recipients
Project Title: Microbiome Profiling as a Marker for Rejection in Heart Transplantation
Summary:
Despite improvement in heart transplant survival rates, rejection of the transplanted heart continues to contribute to morbidity and mortality. Identifying patients at increased risk for graft rejection and failure remains a major challenge. Dr. Nguyen’s clinical research and Dr. Alegre’s laboratory investigations have found that changes in the microbiome can lead to higher rates of transplant rejection. In their DFI-funded study, they will extend their findings by investigating a large cohort of heart transplant recipients and reconstituting germ free mice with fecal microbiota from patients with different degrees of alloimmunity and graft rejection. Their discoveries may enable the use of the peri-transplant microbiome as a biomarker to identify patients at greater risk of graft damage and lead to interventions that enhance the microbiome to improve heart transplant outcomes.
Project Title: Human Mucosal Lymph Node Compartments as Local Responders to the Microbiome
Summary:
In this study, Drs. Esterhazy and Madariaga will investigate human lymph nodes (LNs) draining the gut and lung and correlate functional differences with anatomic location. They will also investigate the impact of the lung and gut microbiota on LN cellular compositions and functions. Their collaboration enables them to systematically identify compartmentalized adaptive immune LN responses in human tissues and to develop insights into the lung-gut axis. Identifying the driving forces that lead to diverse immune environments may have broad clinical impacts in the areas of allergy, autoimmunity, oncology and infectious disease and may lead to novel therapeutic interventions.
Project Title: Understanding the Relationship of Gut Microbiome and Immune Response in Critically Ill Patients
Summary:
In their study, Drs. Wolf and Tay will narrow the gap in understanding of sepsis pathophysiology by investigating how differences in the gut microbiome composition impact host immune responses. They aim to create a comprehensive profile of the immune response in patients using a multiplex and novel digital assay developed by Dr. Tay’s laboratory. Using that profile, they will build a comprehensive database of clinical, immune, and microbiome markers to develop accurate outcome prediction models using machine learning algorithms, with the goal of developing tools to quickly identify high-risk patients that may benefit from microbiome-directed interventions in future clinical trials.
Project Title: The Effect of Fiber Supplementation on Oral Immunotherapy Outcomes in Children with Peanut Allergy
Summary:
Drs. Ciaccio and Nagler will investigate the impact of potato starch versus corn starch as prebiotics to enhance the effectiveness of oral immunotherapy (OIT) for children with peanut allergy. They hypothesize that administration of potato starch will induce allergy-protective changes in intestinal bacterial abundance and function. They further hypothesize that bacterial responses to potato starch will improve the safety and efficacy of OIT by regulating the intestinal barrier during treatment. By positively manipulating the gut microbiome during OIT, they may affect the manner in which OIT interacts with the mucosal immune system, impacting both short- and long-term efficacy.
Project Title: Gut Dysbiosis After Acute Brain Injury: Profiling and Associations with Clinical Trajectories and Neurologic Outcomes
Summary:
Drs. Chang and Lazaridis will study the complex relationships within the microbiota-gut-brain axis in a novel, prospective longitudinal study of gut microbiota in patients with traumatic brain injury or following ischemic and hemorrhagic stroke. They will study the incidence, patterns, and temporal nature of gut dysbiosis in patients with different types of acute brain injury (ABI). Further, they will investigate fecal metabolomes as a biomarker in ABI, and explore associations with clinical trajectories, neurologic outcomes and phenotypes of traumatic brain injury and stroke.
Project Title: Gut Microbiota-Mediated Modulation of Abeta Deposition and Microglial Phenotypes in Mouse Models
Summary:
The gut microbiome of Alzheimer’s disease patients has decreased microbial diversity and is compositionally distinct from age- and sex-matched healthy controls. Drs. Mastrianni and Sisodia will study the impact of the microbiota from subjects with Alzheimer ‘s disease (AD) on microglial transcriptomes and levels of deposited Abeta in a mouse model of AD. They anticipate that FMT from Alzheimer's subjects, but not from control healthy donors, will induce pathologic Abeta deposition and microglial transcription in recipient mice. Ultimately, this study may enable identification of microbiota compositions and metabolite profiles that predispose to AD.