ИСТИНА

Gastrointestinal tract (GIT) is the only way of nutrients entry into the body. It hosts the commensal bacteria that affect diverse physiological functions via the metabolites. Despite plenty of studies investigate GIT function, much less is known about GIT adaptation to the conditions of spaceflight. Interpretation of human data is complicated due to heterogeneity of the subjects, diet, use of countermeasures, thus underscoring the need for animal studies in the standard laboratory setting. This study was aimed to investigate the dynamics of functional and morphological changes of the intestine using hindlimb unloading model. A total of 120 BALB/c mice were subject to 30 days of hindlimb unloading (HLU) with subsequent 7-day recovery. Data was collected before (dd -7, -3) over 30 days of unloading (dd 1, 3, 7, 10, 15, 30) and after the reloading (dd 30+3, 30+7). Total transit time, intestinal contractility (jejunum and colon segments), permeability to FITC-inulin (in vivo) and Blue#1 (in vitro), villus / crypta length and muscle layer thickness were measured. Total transit time (TT) increased during HLU and recovered quickly after reloading. The most pronounced differences (+70%) were observed on d10 compared to baseline data in the same animal. While spontaneous contractions of the isolated jejunum segments were unchanged, the sensitivity to the calcium channel blocker nifedipine was transiently enhanced on d14 and to the inhibiting action of phenylephrine by d30. Colon segments displayed inhibited sensitivity (EC50) to carbachol starting from HLU d 14 and inhibited response to adrenoreceptor agonist phenylephrine as soon as d3 of HLU. The intestinal wall muscle layer thickness gradually increased in the medial and, more so, in the distal, but not the proximal part of the small intestine. Thus, changes of adreno- and cholinoreceptor sensitivity and smooth muscle hyperplasia might underlie the increased transit time found in vivo. The intestinal wall permeability to FITC-inulin increased by 30% by the 14th day of HLU and remained elevated for the next two weeks of exposure. Similarly, permeability to Blue#1 in the isolated jejunum segments (everted sac preparation) increased by 2 weeks of suspension and remained elevated till prompt recovery after the reloading. At the same time, the rate of water absorption in the same preparations did not change. The villus height, crypt depth, and the ratio of villus height to crypt depth in the small intestine of hindlimb unloaded mice did not change. Thus, the wall permeability to FITC-inulin and Blue#1 during unloading may be due to the density of contacts between epithelial cells but not due to a change in the absorptive surface area. We conclude that the changes of intestinal contractility, morphology and transit time are an adaptation to change of gravity direction relative to body axis in the hindlimb unloaded animals. The increased intestinal wall permeability might have negative implications for the health of the subject as the disruption of the intestinal barrier presents a root for bacterial invasion.