Our project will test the effects of space flight and ground-based simulations of microgravity on the function of the lymphatic system of the intestines and potential effects this may have on the immunology, nutrition and microbiomics of animals. The lymphatic system of the intestine serves to transport lipid nutrients from the lumen of the gut to the systemic circulation while simultaneously sampling antigen and transporting immune cells from the tissue to the lymph node and returning fluids and proteins leaked from the blood vasculature to the systemic circulation. The gut is host to the greatest number of non-self organisms in the body and the lymphatic system is key to monitoring this interaction through antigen sampling and regulation of nutrient load in the gut. Dysfunction of the lymphatic system in the gut leads to inflammation due to impaired clearance of cells, fluid and debris from the tissue and impaired host microbiome interaction through loss of immunological tolerance to the commensal microbes and impaired lipid uptake as well as protein shedding from the tissue into the lumen of the gut which causes shifts in the microbiome constituents.
Fluid Shift Associated Lymphostasis of the Gut Induces Inflammation and Microbial Intolerance (First Award Fellowship)
Walter Cromer, Ph.D.
Texas A&M University Health Science Center
We are using tissues harvested from the gut of space flown animals as well as ground based simulations of microgravity to determine lipid transport (via Oil-red-O staining), the number and morphology of lymphatic vessels in the tissue (via immunohistochemistry of lymphatic endothelial cell markers) and the general inflammatory state of the tissue (via histopathological analysis and cytokine array analysis of the tissue). This will provide clues to the alteration of the host lymphatic function and system status however this will be augmented by the analysis of the microbiome of the animals. We are using shotgun 16s rRNA sequencing to determine the alterations of the microbiome and comparing these changes to known pathologies to determine potential downstream effects and predict potential successful therapeutics such as anti-inflammatories or pro-biotic supplementation.
Well over 2.6 million individuals in the United States alone have some form of chronic bowel disease associated with lymphatic dysfunction (Crohn’s Disease, Ulcerative Colitis, Intestinal Lymphangectasia) and our work with NASA is providing important insights into the early stages of these disease and how disrupted lymphatic function early in the disease process can translate to chronic inflammation. Additionally we are working on methods to detect this reduced lymphatic function during disease as an early indicator of inflammation which would be invaluable to better management of disease treatment.