Fluid Shift Associated Lymphostasis of the Gut Induces Inflammation and Microbial Intolerance (Postdoctoral Fellowship)
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POSTDOCTORAL FELLOWSHIP Original Aims: The original aims were to determine if there were inflammation in the intestines of rodents resulting from space flight, measure signs of lymphatic insufficiency in the intestine of space flown animals, examine lymphatic vessel/immune cell interaction in tissues of ground based analogs of microgravity, and determine if shifts in the microbiome of ground based microgravity analogs are analogous to those in space flight and check associated nutrition status. Key Findings: We found evidence of inflammation in the intestines of rats flown for short duration (9 day), low Earth orbit (shuttle PARE 0.3) including edema and immune cell infiltration (via histopathology). This was supported by cytokine analysis that revealed that several key cytokine protein levels (IL-4, IL-5, IP-10, RANTES, etc.) were up-regulated in the intestinal tissues of space flown animals and the profile suggests the initial phases of an inflammatory state. We also observed signs of lymphatic dysfunction with increased lipid droplet staining in the villi of the ileum and collapsed lymphatic vessels in the bowel wall of the colon that when considered together in the context of inflammation suggest a lymphatic functional deficiency. It is also likely that this dysfunction, at least in acute space flight, originates at the capillary lymphatic level given our observations of failed lipid uptake and collapsed pre-collecting lymphatic vessels with no other obvious signs of structural aberrations (no changes in perimeter of breaks in lymphatic endothelial staining). We were able to observe changes in the nature of lymphatic vessel/immune cell interactions in ground based models of microgravity in rats and mice (this is a critical regulator of lymphatic function) but not in space flown rats as the tissue was not available. We found that the number of MHCII positive antigen presenting cells (APCs) were decreased along mesenteric lymphatic collecting vessels in both mice and rats after 4 weeks of suspension. This was accompanied by a concomitant increase in number of potentially fibrotic CD146/CD206(int/low) macrophages along the vessels. We unfortunately were not able to test the antigen uptake and processing efficiency of the remaining APCs. We were able to perform limited micobiomic analysis of rat and mouse feces from simulated microgravity but have not yet received the comparison data for similar space flight animals. Our data suggests that rats in simulated microgravity have a shift in the microbiome similar to that of an animal fed a high fat diet with some aspect of immune suppression while similar samples from mice appear to resemble that from inflammatory bowel diseases. We were not able to complete nutritional analysis of the stools of space flown animals; however, lipid staining of the colon revealed that there was excessive lipid in the colon of space flown animals suggesting that fats are not being efficiently absorbed. Impact.........