Endoplasmic reticulum stress influences the localization of prion protein in the small intestine and mesenteric lymph nodes

Tunicamycin is an endoplasmic reticulum (ER) stressor that inhibits protein glycosylation and promotes ER stress. To better understand the localization and traffic of prion protein (PrP) in both basal and ER stress conditions, we evaluated the presence and relative expression of PrP in the intestinal compartments of normal and tunicamycin-treated mice. After tunicamycin treatment, the level of PrP was significantly increased in enterocytes and blind-ended villous lymphatic vessels (lacteals), but was decreased in M cells. These results suggested that intake from the gut and transfer into lymphoid compartments of basal PrP occurs largely through the M cell-Peyer?s patch-mesenteric lymph node axis, and also alternatively through the enterocyte-lacteal-mesenteric lymph node axis. In ER stress, the enterocyte-lacteal-mesenteric lymph node is the sole axis for PrP transmission. Results also indicated that germinal centers and high endothelial venules (HEVs) are the most prominent portal for entry of PrP in both basal and ER stressed conditions. We speculated that PrP may use alternative routes for entry into intestinal compartments according to the pathophysiological state and that the mechanism managing the routes of PrP could contribute to the development of new therapeutic strategies against prion diseases as well as ER stress-related intestinal disorders.

LECTINS IN ANTI-CANCER STRATEGIES

The published during last few years data concerning communicative role of lectins (proteins and their complexes which recognize carbohydrates, glycoconjugates and their patterns) in on-duty supporting and increasing anticancer status of human immunity are analyzed. Examples of lectin-(glycoconjugate pattern) strategies, approaches and tactic variants in study and development of anticancer treatments, principle variants of therapy, possible vaccines in 35 cases of blood connected tumors (leukemia, lymphomas, others), solid tumors (carcinomas, sarcoma, cancers of vaginal biotopes, prostate, bladder, colon, other intestinal compartments, pancreas, liver, kidneys, others) and cancer cell lines are described and systemized. The list of mostly used communicative lectins (pattern recognition receptors, their soluble forms, other soluble lectins possessing specificities of importance) involving in key intercellular cascades and pathway co-functioning is presented. The regulation of resulting expression of distinct active lectins (available and hetero/di/oligomeric forms) and their interaction to adequate glycoconjugate patterns as well as influence distribution of co-functioning lectins and antigens CD between populations and subpopulations of antigen-presented cells (dendritic cells cDC, mDC, moDC, pDC; macrophages M2 and M1), mucosal M-cells, NK-cells play key role for choice and development of anticancer complex procedures increasing innate and innate-coupled immune responses. Prospects of (receptor lectin)-dependent intercellular communications and targeting glycoconjugate constructions into innate immunity cells for therapy of cancer and development of anticancer vaccines are evaluated and discussed.

Gut segments outweigh the diet in shaping the intestinal microbiome composition in grass carp Ctenopharyngodon idellus

ABSTRACTAlthough dynamics of the complex microbial ecosystem populating the gastrointestinal tract of animals has profound and multifaceted impacts on host’s metabolism and health, it remains unclear whether it is the intrinsic or extrinsic factors that play a more dominant role in mediating variations in the composition of intestinal microbiota. To address this, two strikingly different diets were studied: a high-protein, low-fiber formula feed (FF), and low-protein, high-fiber Sudan grass (SG). After a 16-week feeding trial on a herbivorous fish, grass carp, microbial profiles of midgut (M) and hindgut (H) segments of both groups were compared. Bacteroidetes were more abundant in the hindgut (T=-7.246, p<0.001), and Proteobacteria in the midgut (T=4.383, p<0.001). Fusobacteria were more abundant in the FF group (compared to the SG group, T=2.927, p<0.001). Bacterial composition was different (p<0.05) between the midguts of formula feed (M-FF) and Sudan grass (M-SG) groups, but not between the hindguts of two groups (H-FF and H-SG; p=0.269). PerMANOVA and VPA indicated that the gut segment contributed 19.8% (p<0.001) and 28% (p<0.001) of the variation of microbial communities, whereas diet contributed only 8.0% (p<0.001) and 14% (p<0.001), respectively. Overall, results suggest that intestinal compartments are a stronger determinant than diet in shaping the intestinal microbiota. Specifically, whereas diet has a strong impact on the microbiome composition in proximal gut compartments, this impact is much less pronounced distally, which is likely to be a reflection of a limited ability of some microbial taxa to thrive in the anoxic environment in distal segments.IMPORTANCEThe impact of compositional dynamics of gut microbiota on host’s metabolism and health is so profound that the traditional idea of biological individual is increasingly replaced with "holobiont", comprising both the host and its microbiome. Composition of gut microbiota is strongly influenced by extrinsic (such as diet) and intrinsic (such as gut compartment) factors. Despite ample scientific attention both of these factors have received individually, their relative contributions in mediating the dynamics of the microbiome remain unknown. Given the importance of this issue, we set out to disentangle their individual contributions in a herbivorous fish, grass carp. We found that intestinal compartments are a stronger determinant than diet in shaping the intestinal microbiota. Whereas the impact of diet is strongly pronounced in proximal gut compartments, it appears that limited ability of some microbial taxa to thrive in the anoxic environment in distal segments strongly reduces the impact of diet distally.

Comparison of Nitrogen Bioaccessibility from Salmon and Whey Protein Hydrolysates using a Human Gastrointestinal Model (TIM-1)

Background: The TIM-1 system is a computer-controlled multi-compartmental dynamic model that closely simulates in vivo gastrointestinal tract digestion in humans. During digestion, the compounds released from meal matrix by gastric and intestinal secretions (enzymes) are progressively absorbed through semipermeable membranes depending on their molecular weight. These absorbed (dialysed) compounds are considered as bioaccessible, which means that they can be theoretically absorbed by the small intestine in the body.Methods: Salmon protein hydrolysate (SPH), whey protein hydrolysates extensively (WPH-High) or weakly (WPH-Low) hydrolysed, non-hydrolysed whey protein isolate (WPI) and mixtures of WPI:SPH (90:10, 80:20) were digested in TIM-1 using the conditions for a fast gastrointestinal transit that simulate the digestion of a liquid meal in human adults. During digestion (2 hours), samples were collected in intestinal compartments (duodenum, jejunum, and ileum) and in both jejunal and ileal dialysates to determine their nitrogen content. All the products were compared in terms of kinetics of nitrogen absorption through the semipermeable membranes (bioaccessible nitrogen) and nitrogen distribution throughout the intestinal compartments at the end of the 2 hour digestion.Results: After a 2 h-digestion in TIM-1, SPH was the protein substrate from which the highest amount of nitrogen (67.0%) becomes available for the small intestine absorption. WPH-High had the second highest amount (56.0%) of bioaccessible nitrogen while this amount decreased to 38.5–42.2% for the other protein substrates. The high nitrogen bioaccessibility of SPH is consistent with its richness in low molecular weight peptides (50% < 1000 Da).Conclusions: The results of this study indicate that SPH provides a higher proportion of bioaccessible nitrogen to a healthy adult compared to all forms of whey proteins, including extensively hydrolysed whey protein hydrolysate. The substitution of non-hydrolysed WPI by small amounts of SPH (10–20%) improved slightly its nitrogen bioaccessibility, making the mixture particularly suitable for applications such as medical foods that require rapid protein uptake and where the use of extensively hydrolysed whey protein is unfeasible due to its undesirable organoleptic properties.Keywords: Salmon protein hydrolysate, Whey protein, Nitrogen bioaccessibility, TIM-1

Small intestinal segment perfusion test in piglets: future applications in studying probiotics-gut crosstalk in infectious diarrhoea?

Worldwide infectious diarrhoea, mainly caused by rotavirus and enterotoxigenic Escherichia coli (ETEC), accounts for a large part of deaths in children. ETEC is also the main cause of traveller's diarrhoea. Probiotics are promising for prevention and treatment of diarrhoea, but there is insufficient evidence to support the use of any specific probiotic or probiotics in general. Because of the sensitivity of suckling and weaned piglets for ETEC, piglets are a good model for infectious diarrhoea in infants and traveller's diarrhoea. Just as in human the efficacy of probiotics in diminishing diarrhoea and improving growth in suckling and weaned piglets is not uniform. A piglet model of infectious diarrhoea provides access to intestinal compartments that are not easily accessible in infants. In an in situ piglet model of secretory diarrhoea, the functional physiological response to ETEC and the concomitant host genome response to ETEC and probiotics may be tested. This will provide new insights in the complex crosstalk between ETEC, probiotics and the gut in the future.