Intestinal epithelial cell (IEC) junctions constitute a robust barrier to invasion by viruses, bacteria and exposure to ingested agents. Previous studies showed that microgravity compromises the human immune system and increases enteropathogen virulence. However, the effects of microgravity on epithelial barrier function are poorly understood. The aims of this study were to identify if simulated microgravity alters intestinal epithelial barrier function (permeability), and susceptibility to barrier-disrupting agents. IECs (HT-29.cl19a) were cultured on microcarrier beads in simulated microgravity using a rotating wall vessel (RWV) for 18 days prior to seeding on semipermeable supports to measure ion flux (transepithelial electrical resistance (TER)) and FITC-dextran (FD4) permeability over 14 days. RWV cells showed delayed apical junction localization of the tight junction proteins, occludin and ZO-1. The alcohol metabolite, acetaldehyde, significantly decreased TER and reduced junctional ZO-1 localization, while increasing FD4 permeability in RWV cells compared with static, motion and flask control cells. In conclusion, simulated microgravity induced an underlying and sustained susceptibility to epithelial barrier disruption upon removal from the microgravity environment. This has implications for gastrointestinal homeostasis of astronauts in space, as well as their capability to withstand the effects of agents that compromise intestinal epithelial barrier function following return to Earth.

Despite recent drug approvals for the treatment of inflammatory bowel diseases (IBD), there remains a high unmet need for new technologies that can increase drug efficacy by improving site-specific drug delivery while reducing systemic exposure. These technologies must address challenges with formulation; in particular, drugs that are liquid, peptides or proteins are difficult to formulate using existing delayed and extended oral release technologies. They also have the potential to improve efficacy and reduce systemic exposure for certain drugs by delivering higher doses directly to the site of inflammation. A novel drug delivery system (DDS2) is being developed for delivery at a pre-specified part of the gastrointestinal tract. This autonomous mechanical capsule uses an algorithm based on reflected light to deliver soluble formulations of drugs to the predefined location. This system has significant advantages over other traditional delayed release oral formulations because it functions independently of human physiological variables such as pH and transit time and can deliver liquid formulations, peptides, and proteins. Such a system can ensure a predictable high luminal drug exposure and limited degradation or systemic absorption in the upper gastrointestinal tract and would therefore be ideal for treatment of disorders such as IBD and colon cancer.

No abstract

Figure 1. A) Alpha-diversity box plots comparing the duodenal microbial diversity in the Tonsillectomy group (T1), and the no Tonsillectomy group (T-), as determined using 3 different indices, Shannon's, Simpson's and Chao1. B) Principal Component Analysis (PCA) plot of the duodenal microbiome beta-diversity of Tonsillectomy group (T1) compared to no Tonsillectomy group (T-). C) Heat tree illustrating minimal changes to the microbiome in subjects who reported undergoing a tonsillectomy (T1) relative to those who did not (T-). Nodes represent taxonomic levels, and greater line thickness denotes greater relative abundance. Taxa with higher relative abundance in the T1 group when compared to the T-group are shown in red. Taxa with higher relative abundance in the T-group when compared to the T1 group are shown in blue. Taxa with similar relative abundance in both groups are shown in gray