Responses of Intestinal Mucosal Barrier Functions of Rats to Simulated Weightlessness

Abstract

Exposure to microgravity or weightlessness leads to various adaptive and pathophysiological alterations in digestive structures and physiology. The current study was carried out to investigate responses of intestinal mucosal barrier functions to simulated weightlessness, by using the hindlimb unloading rats model. Compared with normal controls, simulated weightlessness damaged the intestinal villi and structural integrity of tight junctions, up-regulated the expression of pro-apoptotic protein Bax while down-regulated the expression of anti-apoptotic protein Bcl-2, thus improved the intestinal permeability. It could also influence intestinal microbiota composition with the expansion of Bacteroidetes and decrease of Firmicutes. The predicted metagenomic analysis emphasized significant dysbiosis associated differences in genes involved in membrane transport, cofactors and vitamins metabolism, energy metabolism, and genetic information processing. Moreover, simulated weightlessness could modify the intestinal immune status characterized by the increase of proinflammatory cytokines, decrease of secretory immunoglobulin A, and activation of TLR4/MyD88/NF-κB signaling pathway in ileum. These results indicate the simulated weightlessness disrupts intestinal mucosal barrier functions in animal model. The data also emphasize the necessity of monitoring and regulating astronauts’ intestinal health during real space flights to prevent breakdowns in intestinal homeostasis of crewmembers.

Intestinal microbiota contributes to altered glucose metabolism in simulated microgravity mouse model

“…Recently, we and others have found similar microbial changes at phyla levels in HU rodent models (30)(31)(32). The villus morphology and epithelial cell homeostasis, either in the colon or small intestine, were also altered (30,31).…”

“…Recently, we and others have found similar microbial changes at phyla levels in HU rodent models (30)(31)(32). The villus morphology and epithelial cell homeostasis, either in the colon or small intestine, were also altered (30,31). This altered microbiota-epithelium crosstalk resulted in exacerbated colitis when the epithelial barrier was further injured or infected (33,34).…”

“…The gut microbiota plays a critical role in endotoxemiainduced chronic inflammation and the onset of metabolic diseases (17,43). In 3-wk HU rats, decreased expression of tight junction-related proteins in ileum and increased serum endotoxin level had been found (30). We thus measured the levels of plasma LBP, which were closely correlated with plasma LPS and the intensity of TLR4 signaling triggered by LPS (44,45).…”

Medicina humana espacial: Performance fisiológico y contramedidas para mejorar la salud del astronauta

“…309 solares (rayos γ, rayos X) y al estrés inducido por la microgravedad (74) , ocasionando alteraciones en la inmunidad celular, en la formación de leucocitos, citocinas e inhibición de la actividad fagocítica de granulocitos, monocitos y macrófagos, incluidas las subpoblaciones de linfocitos T (T hellper 1, T hellper 2); B y NK. De igual forma, el factor nuclear kappa de células B activadas (NF-Kb) se ven afectadas y disminuyen la producción de citocinas (IL-1, IL-6, IL-12 y Factor de necrosis tumoral alfa TNF-α) (74,75,76) .…”

“…Igualmente existen alteraciones en la motilidad, microbiota intestinal, metabolismo de glucosa y lípidos (89,90) , daño de las vellosidades intestinales e interrupción en las uniones celulares epiteliales por la expresión de la proteína proapoptótica Bax y disminución de Bcl2; alterando de esta manera su función defensiva, homeostasis y el riesgo de contraer enfermedades inflamatorias intestinales (76,91,92,93) por el aumento de citosinas y disminución de la inmunoglobulina secretora (IgA) (76) .…”