The Intestinal Mucus Layer is a Critical Component of the Gut Barrier that is Damaged During Acute Pancreatitis

Abstract

Background Gut barrier failure has been implicated in the progression from single organ injury to multiple organ failure. The unstirred mucus layer is a major component of the physiological gut barrier, its role in acute pancreatitis(AP) is not clearly defined. Study Design Rats underwent biliopancreatic duct ligation-induced AP; two controls were used: biliopancreatic duct ligation with drainage and sham duct ligation. After 4.5 hours, serum and ascitic amylase activity was measured. Mucus was analyzed for reactive nitrogen intermediates(RNI)-mediated damage, reactive oxygen species(ROS)-induced damage, and total antioxidant capacity. Mucus coverage and villous injury was assessed histologically. Ileum permeability was measured by diffusion of a fluorescent dextran probe. Histology and morphology of the mucus layer were validated in a mouse AP model (intraductal taurocholate plus caerulein). Results Biliopancreatic duct ligation increased serum α-amylase, ascitic volume, and ascitic α-amylase. Intestinal permeability was increased, which was associated with loss of the unstirred mucus layer but not villous injury. These changes correlated with increased ROS-and-RNI-mediated mucus damage as well as decreased mucus total antioxidant capacity but were not present in the two control groups. Using a different model of AP in mice, the finding of mucus layer disruption was recapitulated at 6 hours after AP, but by 24 hours, rebound hypersecretion of inspissated mucus was seen. Conclusions These results support the hypothesis that damage to the unstirred mucus layer with evidence of oxidative stress occurs during AP-induced gut barrier failure.

Effects of n-3 PUFAs on Intestinal Mucosa Innate Immunity and Intestinal Microbiota in Mice after Hemorrhagic Shock Resuscitation

“…The present study revealed that 90 min of hemorrhagic shock followed by resuscitation decreased the levels of lysozyme and mucin 2, consistent with previous reports in different mouse models of IR [11,13,24]. Consequently, decreased lysozyme and mucin 2 levels in the intestinal mucosa may contribute to increased bacterial translocation after HSR [25]. …”

“…However, it remains to be determined why n -6 PUFAs, but not lysozyme, enhanced the expression of mucin 2, but not lysozyme, IL-4, or IL-10. In addition, n -6 PUFAs also ameliorated bacterial translocation after HSR in MLN, possibly through increased mucin 2 expression [25]. It should be noted, however, that exogenous addition of n -3 PUFAs or n -6 PUFAs failed to revert the low expression of the antibacterial lectin RegIIIγ.…”

Autodigestion

“…The mucosal barrier is well recognized for its ability to prevent undigested food or bacteria from passing across the epithelial cells into the mucosal space of the intestinal villi (16,17). In the context of the current discussion, the intestinal mucosal barrier serves to compartmentalize the digestive enzymes inside the lumen of the intestine.…”

Prostaglandin E 2 constrains systemic inflammation through an innate lymphoid cell–IL-22 axis

“…S13); two inducible enzymes that mediate PGE 2 synthesis (4). Acute pancreatitis (AP) is a sterile initiator of systemic inflammation that results in multiple organ dysfunction where gut barrier injury is central to the pathogenesis (30). Given that IL-22 was protective in an animal model of AP (31), we measured IL-22 levels in patients with AP.…”