Goblet cells (GCs) are single-cell glands that produce and secrete mucin. Mucin forms a mucus layer, which can separate the materials in cavities from the intestinal epithelium and prevent the invasion of pathogenic microorganisms in various ways. GCs can also participate in the immune response through nonspecific endocytosis and goblet cell-associated antigen passages (GAPs). GCs endocytose soluble substances from the lumen and transmit antigens to the underlying antigen-presenting cells (APCs). A variety of immuno-regulatory factors can promote the differentiation, maturation of GCs, and the secretion of mucin. The mucin secreted by GCs forms a mucus layer, which plays an important role in resisting the invasion of foreign bacteria and intestinal inherent microorganisms, regulating the immune performance of the body. Therefore, the present study mainly reviews the barrier function of the mucus layer, the mucus secreted by goblet cells, the protective effect against pathogenic bacteria, the delivery of luminal substances through GAPs and the relationship between GCs and the immune response.

Enterotoxigenic Escherichia coli (ETEC) is a common diarrheal pathogen in humans and animals. To prevent and treat ETEC induced diarrhea, we synthesized mannan oligosaccharide selenium (MOSS) and studied its beneficial effect on ETEC-induced diarrhea. A total of 32 healthy weaned piglets (6.69 ± 0.01 kg) were randomly divided into four groups: NC group (Basal diet), MOSS group (0.4 mg/kg MOSS supplemented diet), MOET group (0.4 mg/kg MOSS supplemented diet + ETEC treatment), ETEC group (ETEC treatment). NC and ETEC group fed with basal diet, MOSS and MOET group fed with the MOSS supplemented diet. On the 8th and 15th day of the experiment, MOET and ETEC group were gavaged with ETEC, and NC and MOSS group were gavaged with stroke-physiological saline solution. Our data showed that dietary MOSS supplementation increased average daily gain (ADG) and average daily feed intake (ADFI) and significantly decreased diarrhea index and frequency in ETEC-treated piglets. MOSS did not affect the α diversity and β diversity of ileal microbial community, but it significantly decreased the proportion of lipopolysaccharide biosynthesis in ileal microbial community. MOSS supplementation regulated colonic microbiota community composition, which significantly increased carbohydrate metabolism, and inhibited lipopolysaccharide biosynthesis pathway in colonic microbial community. Moreover, MOSS significantly decreased inflammatory stress, and oxidative stress in ETEC treated piglets. Furthermore, dietary MOSS supplementation significantly decreased intestinal barrier permeability, and alleviated ETEC induced intestinal mucosa barrier irritation. In conclusion, our study showed that dietary MOSS supplementation ameliorated intestinal mucosa barrier, and regulated intestinal microbiota to prevent ETEC induced diarrhea in weaned piglets.

Endotoxins are toxic substances that widely exist in the environment and can enter the intestine with food and other substances. Intestinal epithelial cells are protected by a mucus layer that contains MUC2 as its main structural component. However, a detailed understanding of the mechanisms involved in the function of the mucus barrier in endotoxin penetration is lacking. Here, we established the most suitable proportion of Caco-2/HT-29 co-culture cells as a powerful tool to evaluate the intestinal mucus layer. Our findings significantly advance current knowledge as focal adhesion and ECM-receptor interaction were identified as the two most significantly implicated pathways in MUC2 small interfering RNA (siRNA)-transfected Caco-2/HT-29 co-culture cells after 24 h of LPS stimulation. When the mucus layer was not intact, LPS was found to damage the tight junctions of Caco-2/HT29 co-cultured cells. Furthermore, LPS was demonstrated to inhibit the integrin-mediated focal adhesion structure and damage the matrix network structure of the extracellular and actin microfilament skeletons. Ultimately, LPS inhibited the interactive communication between the extracellular matrix and the cytoskeleton for 24 h in the siMUC2 group compared with the LPS(+) and LPS(-) groups. Overall, we recognized the potential of MUC2 as a tool for barrier function in several intestinal bacterial diseases.

Swainsonine (SW), an indolizidine alkaloid extracted from locoweeds, was shown toxic effects in multiple studies, but the underlying action mechanism remains unclear. SW is known to cause autophagy and apoptosis, but there has been no report on paraptosis mediated cell death. Here, we showed that SW induced rat primary renal tubular epithelial cells (RTECs) death accompanied by vacuolation in vitro. The fluorescence with the endoplasmic reticulum (ER)-Tracker Red and transmission electron microscopy (TEM) results indicated that the vacuoles were of ER origin, typical of paraptosis. The level of ER stress markers, such as polyubiquitinated proteins, Bip, CHOP and cytoplasmic concentration of Ca²⁺ have drastically increased. Interestingly, autophagy inhibitor could not interrupt but enhanced the induction of cytoplasmic vacuolization. Furthermore, MAPK pathways were activated by SW and inhibitors of ERK and JNK pathways could prevent the formation of cytoplasmic vacuolization. In this study, we confirmed that SW induced cell paraptosis through ER stress and MAPK signaling pathway, thus further laying a theoretical foundation for the study of SW toxicity mechanism.