Jejunal Absorption Research Articles

Host or the Hosted? Effects of Non-Nutritive Sweeteners on Intestinal and Microbial Mechanisms of Glycemic Control.

Background/Objective: High habitual consumption of non-nutritive sweeteners (NNS) is linked to increased incident type 2 diabetes, with emerging clinical evidence that effects on gut microbiota may, in part, drive this risk. However, the precise contribution of the effects of NNS on gut microbiota to host glycemic responses remains unclear. Methods: Ten-week-old male C57BL/6 mice (N = 10 per group) were randomized to drinking water with or without combined NNS (sucralose 1.5 mg/mL plus acesulfame-K 2.5 mg/mL) and with or without antibiotics to deplete gut microbiota (ABX, 1 mg/mL ampicillin and neomycin) over two weeks. Oral glucose tolerance tests (OGTT, 2 g/kg) were conducted on days -1 and 12. On day 14, mice underwent a jejunal infusion of glucose (300 mg) with 3-O-methyl glucose (30 mg, 3-OMG, a marker of glucose absorption) in 1.5 mL for 30 min, followed by blood collection and bioassays. Data were analyzed using ANOVA with NNS and ABX as factors. Results: Jejunal glucose absorption was augmented in NNS+ mice relative to NNS- (31%; 3-OMG T30; p ≤ 0.05) independent of ABX. ABX attenuated OGTT responses independent of NNS supplementation (-35%; incremental AUC, p ≤ 0.001). NNS+ ABX+ mice had augmented GLP-1 responses to intrajejunal glucose relative to other groups (69-108%, p < 0.05). Conclusions: These findings demonstrate that sub-acute NNS supplementation augments glucose absorption independent of gut microbiota in mice but does not disrupt glycemic responses. Antibiotic depletion of gut microbiota markedly increased glucose tolerance in mice, which may involve the actions of GLP-1.

Signals from the dorsal motor nucleus of the vagus promote jejunal fat absorption.

Signals from the dorsal motor nucleus of the vagus promote jejunal fat absorption.

Thyroxine replacement by colonic route and absorption kinetics: case report

In the literature there are only 2 reports of replacement of thyroid hormones by colonic route. The objective of this study is to present a clinical case where thyroid hormone replacement was performed through the application of enemas with levothyroxine. 78-year-old patient with hypothyroidism is presented who attended to the emergency room with intestinal occlusion, which presented refractory hypothyroidism secondary to intestinal occlusion and she underwent hormone replacement with enemas with levothyroxine. The kinetics of colonic absorption of thyroid hormones takes twice as long to reach the plateau of serum levels with respect to absorption in jejunum and ileum.

An investigation of different antimycotoxin additives in swine intestinal explants challenged with aflatoxin and fumonisin: ex vivo and in vitro models

Abstract This study aimed to develop an ex vivo model to evaluate the efficacy of antimycotoxin additives (AMAs) against aflatoxin B1 (AFB1) and fumonisin B1 (FB1) using intestinal explants of growing pigs. Four assays of two treatments with 12 replicates each (24 jejunal explants used per assay) were performed using an Ussing Chamber (UC) system: two assays to evaluate two AMAs for AFB1 and two assays to evaluate two AMAs for FB1. The difference between the two assays for both AFB1 and FB1 was the composition of the additive used. The treatments for AFB1 assays were control [Buffer solution (BS) + 1 mg/l AFB1] and AMA (BS + 1 mg/l AFB1 + 0.5% AMA 1 or 2). The treatments for FB1 assays were control (BS + 50 mg/l FB1) and AMA (BS + 50 mg/l FB1 + 0.5% AMA 3 or 4). The efficacy of the four additives was also tested in vitro. The AFB1 concentrations in the explants from AMAs 1 and 2 were lower () than in the control. AMAs 1 and 2 reduced the jejunal absorption of AFB1 by 83.4 and 72.9%, respectively. Explants from AMAs 3 and 4 had lower FB1 () concentration when compared to the respective control treatment. AMAs 3 and 4 reduced the FB1 absorption by 31.9 and 17.6%, respectively. In the in vitro test, AMAs 1 and 2 provided 98.4 and 86.3% of AFB1 adsorption, respectively, while AMA 3 and 4 provided 91.2 and 80.5% FB1 adsorption, respectively. The ex vivo model can be a useful tool in evaluating the effectiveness of antimycotoxin additives for AFB1 and FB1 in swine. However, the low FB1 uptake in jejunal explants highlights the need for the development of additional information to improve the method.

145 Dose-Response and Functional Roles of Zinc Glycinate on Growth and Intestinal Health of Nursery Pigs Challenged with F18+Escherichia Coli

Abstract This study was to evaluate dose-response and supplemental effects of zinc glycinate (ZnGly) on growth and intestinal health of nursery pigs challenged with F18+Escherichia coli. Nursery pigs (n = 40; BW = 6.5 ± 0.5 kg) were allotted to 5 treatments in a randomized complete block design with BW and sex as blocks: 1) NC: no-challenge/no-supplement; (2) PC: F18+E. coli challenge/no-supplement; (3 to 5) F18+E. coli challenge/supplementations of ZnGly at 400, 800, and 1,200 mg/kg. On d 7, challenged groups were orally inoculated with F18+E. coli at 6 × 109 CFU/mL, whereas NC received saline solution. Pigs were fed for 28 d based on 2 phases (Phase 1: 14 d and phase 2: 14 d), and experimental diets were formulated to meet or exceed nutrient requirements suggested by NRC (2012). Pigs were euthanized on d 28 to collect tissues to evaluate TNF-α, IL-8, malondialdehyde, protein carbonyl, gene expression of Zn transporters, and mucosa-associated microbiota in the jejunum. Data were analyzed using contrasts in the MIXED procedure of SAS. The E. coli challenge tended to reduce (P = 0.065) ADG (308 to 244 g/d) and increase (P &amp;lt; 0.05) fecal score (3.2 to 4.1) of the pigs during the first week of post-challenge. Supplementation of ZnGly from 0 to 1,200 mg/kg linearly (P = 0.092) increased G:F (0.69 to 0.81) during phase 1 and decreased (P &amp;lt;0.05) fecal score (4.1 to 3.5) of the pigs during the first week of post-challenge. Supplementation of ZnGly from 0 to 1,200 mg/kg had quadratic effects on TNF-α (P = 0.065; minimum 1.51 pg/mg at 405 mg/kg of ZnGly), IL-8 (P = 0.093; minimum 0.53 ng/mg at 494 mg/kg), and protein carbonyl (P = 0.054; minimum 2.30 pg/mg at 675 mg/kg) and linearly increased mRNA expressions of (P = 0.057) ZIP4 (0.69 to 1.03) and (P = 0.075) ZnT5 (0.92 to 1.22) in the jejunum of the pigs. Supplementation of ZnGly from 0 to 1,200 mg/kg tended to linearly decrease (P = 0.065) Chao1 index (150.6 to 144.6) and linearly increased (P &amp;lt; 0.05) relative abundance of Actinobacteria (13.10 to 16.26%) and had quadratic effects (P &amp;lt; 0.05) on the relative abundance of Cyanobacteria (minimum 0.67 % at 625 mg/kg) and Proteobacteria (minimum 45.6% at 735 mg/kg) at the phylum level with Enterobacteriaceae (minimum 4.79% at 660 mg/kg) at family level in jejunal mucosa-associated microbiota of the pigs. In conclusion, supplementation of ZnGly at a range of 400 to 675 mg/kg could reduce the negative impacts of F18+E. coli on growth performance and diarrhea of nursery pigs. These positive changes are related to reducing jejunal inflammation and oxidative stress by enhancing jejunal Zn absorption with positive changes in jejunal mucosa-associated microbiota in the pigs.

Differences in Cholesterol Metabolism, Hepato-Intestinal Aging, and Hepatic Endocrine Milieu in Rats as Affected by the Sex and Age.

Age and sex influence serum cholesterol levels, but the underlying mechanisms remain unclear. To investigate further, we measured cholesterol, precursors (surrogate synthesis markers), degradation products (oxysterols and bile acid precursors) in serum, the liver, jejunum, and ileum, as well as serum plant sterols (intestinal absorption markers) in male and female Wistar rats (4 and 24 months old). The analysis of histomorphometric and oxidative stress parameters (superoxide dismutase, catalase, glutathione-related enzyme activities, lipid peroxide, and protein carbonyl concentrations) in the liver and jejunum offered further insights into the age- and sex-related differences. The hepatic gene expression analysis included AR, ERα, and sex-specific growth hormone-regulated (Cyp2c11 and Cyp2c12) and thyroid-responsive (Dio1, Tbg, and Spot 14) genes by qPCR. We observed age-related changes in both sexes, with greater prominence in females. Aged females had significantly higher serum cholesterol (p < 0.05), jejunum cholesterol (p < 0.05), and serum plant sterols (p < 0.05). They exhibited poorer hepato-intestinal health compared with males, which was characterized by mild liver dysfunction (hydropic degeneration, increased serum ALT, p < 0.05, and decreased activity of some antioxidant defense enzymes, p < 0.05), mononuclear inflammation in the jejunal lamina propria, and age-related decreases in jejunal catalase and glutathione peroxidase activity (p < 0.05). Aged females showed increased levels of 27-hydroxycholesterol (p < 0.05) and upregulated ERα gene expression (p < 0.05) in the liver. Our study suggests that the more significant age-related increase in serum cholesterol in females is associated with poorer hepato-intestinal health and increased jejunal cholesterol absorption. The local increase in 27-hydroxycholesterol during aging might reduce the hepatoprotective effects of endogenous estrogen in the female liver.

Development of active jejunal glucose absorption in broiler chickens

Growth in chickens, especially meat-type chickens (broilers), is extremely rapid, but studies on the regulatory mechanism of intestinal glucose absorption with growth are few, contradictory, and unclear. Here, we investigated the regulation of intestinal glucose absorption with growth in broiler chickens using oral glucose gavage, intestinal Evans blue transit, intestinal glucose absorption, scanning electron microscopy, and glucose absorption- and cell junction-related gene expression analyses. Peak blood glucose levels after oral glucose gavage occurred at 10 and 50 min in chickens at 1 wk (C1W) and 5 wk (C5W) of age, respectively. The area under the curve for glucose levels was greater for the C5W than the C1W (P=0.035). The stain ratio in the small intestine in the C5W was lower than that in the C1W (P=0.01), but there were no differences in the tissue regions stained with Evans blue and the migration distance of Evans blue from Meckel's diverticulum. In everted sac and Ussing chamber experiments, we observed reduced intestinal glucose uptake and electrogenic glucose absorption in the jejunum of the C5W. Phloridzin, an inhibitor of sodium/glucose cotransporter 1 (SGLT1), suppressed the glucose-induced short-circuit current in the C1W (P=0.016) but not the C5W. Although the addition of NaCl solution stimulated the glucose-induced short-circuit current in the C1W, no differences between the treatments were observed (P=0.056), which was also the case in the C5W. Additionally, tissue conductance was diminished in the C5W compared with that in the C1W. Moreover, in the C5W, the intestinal tract was more developed and the jejunal villi were enlarged. In conclusion, glucose absorption throughout the intestine could be greater in C5W than in C1W; however, reduced SGLT1 sensitivity, decreased ion permeability, and intestinal overdevelopment lead to decreased local glucose absorption in the jejunum with growth in broiler chickens. These data provide a detailed analysis of intestinal glucose absorption in growing broiler chickens, and can contribute to the development of novel feeds.

Low sanitary housing conditions increase protein fermentation in piglets but do not aggravate the effects of protein fermentation on intestinal health

Protein fermentation has been identified as a risk factor for the occurrence of post-weaning diarrhea. Associations between low protein digestion – provoking protein fermentation - and low sanitary housing conditions suggest that protein fermentation, low sanitary conditions, and post-weaning diarrhea are interlinked.To this end, an experiment (2×2 factorial treatment arrangement) was performed with 160 weaned female piglets (TN70 х Tempo) divided over 5 batches (4 piglets per pen, 2 pens/treatment/batch). The piglets were kept under high (HSC) or low (LSC) sanitary conditions and were fed a diet low (LiP) or high (HiP) in indigestible protein for 14 days. Fecal consistency was scored daily per piglet and after one week, digesta samples were collected to analyze protein digestibility, colonic flow of protein-derived metabolites, and digesta mean retention time in 2 piglets per pen. Furthermore, we measured intestinal permeability for Fluorescein isothiocyanate-dextran (FITC, 4 kDa) and Tetramethylrhodamine isothiocyanate–dextran (TRITC, 40 kDa), and jejunal absorption capacity for lysine, methionine, and glucose, using the everted gut sac technique.Piglets kept under LSC had 9% units lower apparent total tract protein digestibility than piglets kept under HSC (P < 0.001), mainly explained by 7% units lower apparent ileal protein digestibility in LSC piglets (P < 0.001). Since no relevant correlations were observed between digesta mean retention time and ileal N digestibility and jejunal absorption capacity did not differ between treatment groups, these factors were excluded as underlying causes. The colonic flow of protein-derived metabolites was higher for LSC piglets than for HSC piglets (NH3: +31%, BCFA: +40%, P < 0.001), and higher for HiP piglets than for LiP piglets (NH3: +76%, BCFA: +42% for LSC, +25% for HSC, P < 0.001, SC х Diet P < 0.05). Colonic N disappearance was 5.5% units higher for HiP piglets than for LiP piglets (P < 0.01), but was not affected by SC. Fecal consistency scores were reduced for both HiP (−1.5, P < 0.001) and LSC (−0.5, P < 0.001) piglets compared with LiP and HSC, but no SC х diet interaction was observed. Jejunal permeability was slightly increased for HiP piglets (P < 0.05). No negative effects of feeding HiP on colonic permeability were observed.Low sanitary conditions decrease both ileal and fecal protein digestion to a similar extent and stimulate colonic protein fermentation. It is unlikely that digesta transport or jejunal absorption rates are causal to this effect. There are no indications that housing under low sanitary conditions aggravates the effects of protein fermentation on intestinal health.

Selection for Growth Does Not Affect Apparent Energetic Efficiency of Jejunal Glucose Uptake in Mice

Five-wk-old male mice from high growth (M16) and randomly bred control (ICR) lines, plus their reciprocal crosses, ICR × M16 and M16 × ICR, were used to investigate whether whole-body O2 consumption, jejunal respiration, jejunal glucose absorption and the apparent energetic efficiency of jejunal active glucose uptake in mice are altered by genetic selection for growth as well as by heterosis and maternal effects. Whole-body O2 consumption was measured in 12 mice from each line or cross. The mice were later killed for measurement of jejunal O2, using tissue respiration chambers and jejunal glucose transport determined by 3H-3-O-methylglucose accumulation. No heterosis or maternal effects were detected in jejunal glucose active transport and active glucose uptake. Selection for growth (M16 vs. ICR) increased daily gain (1.54 vs. 1.09 g, P < 0.001), small intestinal length and weight, but did not enhance jejunal glucose transport. The apparent energetic efficiency of jejunal active glucose uptake among lines was not different (54.0, 50.4, 51.6 and 47.1 nmol ATP expended/nmol glucose uptake for M16, ICR, M16 × ICR and ICR × M16, respectively, P > 0.63). Selection for growth in mice did not result in more energetically efficient jejunal glucose absorption.

Morphological Adaptation in the Jejunal Mucosa after Iso-Caloric High-Fat versus High-Carbohydrate Diets in Healthy Volunteers: Data from a Randomized Crossover Study.

Background and aims: The conditions for jejunal glucose absorption in healthy subjects have not been thoroughly studied. In this study we investigated differences in the jejunal villi enlargement factor, as well as ultrastructural aspects of the surface enterocytes and mitochondria, comparing 2 weeks of high-carbohydrate (HCD) versus high-fat diets (HFD). We also measured the ketogenesis rate-limiting enzyme 3-hydroxy-3-methylglutaryl-CoA synthase (HMGCS2) in relation to jejunal mitochondria. Methods: A single-centre, randomized, unblinded crossover study in 15 healthy volunteers ingesting strictly controlled equicaloric diets (either HCD or HFD), with 60% energy from the respective source. An enteroscopy was carried out after 2 weeks of each diet and jejunal mucosal biopsies were acquired. Conventional histology, immunofluorescent staining, transmission electron microscopy and confocal microscopy were used. Results: The villi did not demonstrate any change in the epithelial enlargement factor. Despite an increased mitosis, there were no changes in apoptotic indices. However, the ultrastructural analysis demonstrated a significant increase in the enlargement factor at the bases of the villi. The mitochondria demonstrated increased amounts of cristae after the HFD. The confocal microscopy revealed increased HMGCS2 per mitochondrial marker at the top of the villi after the HFD compared to the HCD. Conclusion: There is a morphometric adaption in the jejunal mucosa following the 2-week diets, not only on a histological level, but rather on the ultrastructural level. This study supports the notion that mitochondrial HMGCS2 is regulated by the fat content of the diet and is involved in the expression of monosaccharide transporters.

The Combination of Plant Extracts and Probiotics Improved Jejunal Barrier and Absorption Capacity of Weaned Piglets

Plant extracts and probiotics play a vital role in maintaining animal intestinal health. However, their joint compatibility program still needs to be further explored. In our study, thirty two piglets (Duroc × Landrace × Yorkshire) were selected to divided into four treatments, which included basal diet, basal diet + 1000 mg/kg probiotics with added glucose oxidase (PGO), basal diet + 500 mg/kg Illicium verum extracts (IVE), and basal diet + 500 mg/kg IVE + 1000 mg/kg PGO. All the piglets were housed individually for the 42-d trial period after 7-d adaptation. Results showed that dietary supplementation of PGO and IVE increased the digestibility of ether extract (EE), crude protein (CP), and lysine (p &lt; 0.05). Likewise, the net protein utilization (NPU) was also improved (p &lt; 0.05). What is more, adding PGO and IVE reduced crypt depth, increased villus length, and chrionic gland ratio of piglets (p &lt; 0.05). Additionally, IVE or PGO that was applied alone can increase the expression of Occludin, Zona occludens 1 (ZO-1), and Sodium-dependent glucose transporters 1 (SGLT1) in jejunum (p &lt; 0.05). Our results strongly suggest that the combination of IVE and PGO can improve the nutrient digestibility of weaned piglets by increasing the expression of nutrient transport vectors (SGLT1 and CAT1) and tight junction proteins (Occludin and ZO-1) in the jejunum. In conclusion, the combination of plant extracts and probiotics is a vital strategy to improve animal health before the advent of antibiotic substitutes with absolute advantages.

A Fatty Diet Induces a Jejunal Ketogenesis Which Inhibits Local SGLT1-Based Glucose Transport via an Acetylation Mechanism-Results from a Randomized Cross-Over Study between Iso-Caloric High-Fat versus High-Carbohydrate Diets in Healthy Volunteers.

Background and aims: Insights into the nature of gut adaptation after different diets enhance the understanding of how food modifications can be used to treat type 2 diabetes and obesity. The aim was to understand how diets, enriched in fat or carbohydrates, affect glucose absorption in the human healthy jejunum, and what mechanisms are involved. Methods: Fifteen healthy subjects received, in randomised order and a crossover study design, two weeks of iso-caloric high-fat diet (HFD) and high-carbohydrate diet (HCD). Following each dietary period, jejunal mucosa samples were retrieved and assessed for protein expression using immunofluorescence and western blotting. Functional characterisation of epithelial glucose transport was assessed ex vivo using Ussing chambers. Regulation of SGLT1 through histone acetylation was studied in vitro in Caco-2 and human jejunal enteroid monolayer cultures. Results: HFD, compared to HCD, decreased jejunal Ussing chamber epithelial glucose transport and the expression of apical transporters for glucose (SGLT1) and fructose (GLUT5), while expression of the basolateral glucose transporter GLUT2 was increased. HFD also increased protein expression of the ketogenesis rate-limiting enzyme mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase (HMGCS2) and decreased the acetylation of histone 3 at lysine 9 (H3K9ac). Studies in Caco-2 and human jejunal enteroid monolayer cultures indicated a ketogenesis-induced activation of sirtuins, in turn decreasing SGLT1 expression. Conclusion: Jejunal glucose absorption is decreased by a fat-enriched diet, via a ketogenesis-induced alteration of histone acetylation responsible for the silencing of SGLT1 transcription. The work relates to a secondary outcome in ClinicalTrials.gov (NCT02088853).

Bile acid transporter-mediated oral absorption of insulin via hydrophobic ion-pairing approach

Despite many ongoing and innovative approaches, there are still formidable challenges in the clinical translation of oral peptide drugs into marketable products due to their low absorption and poor bioavailability. Herein, a novel nanocarrier platform was developed that employs a hydrophobic ion-pairing (HIP) of model peptide (insulin) and the anionic bile salt (sodium glycodeoxycholate, SGDC), and markedly improves intestinal absorption via the bile acid pathway. The developed HIP-nanocomplexes (C1 and C2) were optimized, characterized, and in vitro and in vivo evaluation were performed to assess oral efficacy of these system. The optimal molar ratios of C1 and C2-nanocomplexes were 30:1 and 6:1 (SGDC:insulin), respectively. Compared to the insulin solution, the C1 and C2 nanocomplexes significantly enhanced the permeation of insulin across the Caco-2 cell monolayers, with 6.36- and 4.05-fold increases in apparent permeability, respectively. Uptake mechanism studies were conducted using different endocytosis inhibitors and apical sodium-dependent bile acid transporter (ASBT)-transfected MDCK cells, which demonstrated the involvement of the energy-dependent ASBT-mediated active transport. Furthermore, the intrajejunal administration of C1 and C2 resulted in their pharmacological availabilities (PA) being 6.44% and 0.10%, respectively, indicating increased potential for C1, when compared to C2. Similarly, the PA and the relative bioavailability with intrajejunal administration of the C1 were 17.89-fold and 16.82-fold greater than those with intracolonic administration, respectively, confirming better jejunal absorption of C1. Overall, these findings indicate that the HIP-nanocomplexes could be a prominent platform for the effective delivery of peptides with improved intestinal absorption.

Small intestinal glucose and sodium absorption through calcium‐induced calcium release and store‐operated Ca2+ entry mechanisms

Background and PurposeLuminal glucose enhances intestinal Ca2+ absorption through apical Cav1.3 channels necessary for GLUT2‐mediated glucose absorption. As these reciprocal mechanisms are not well understood, we investigated the regulatory mechanisms of intestinal [Ca2+]cyt and SGLT1‐mediated Na+‐glucose co‐transports.Experimental ApproachGlucose absorption and channel expression were examined in mouse upper jejunal epithelium using an Ussing chamber, immunocytochemistry and Ca2+ and Na+ imaging in single intestinal epithelial cells.Key ResultsGlucose induced jejunal Isc via Na+‐glucose cotransporter 1 (SGLT1) operated more efficiently in the presence of extracellular Ca2+. A crosstalk between luminal Ca2+ entry via plasma Cav1.3 channels and the ER Ca2+ release through ryanodine receptor (RYR) activation in small intestinal epithelial cell (IEC) or Ca2+‐induced Ca2+ release (CICR) mechanism was involve in Ca2+‐mediated jejunal glucose absorption. The ER Ca2+ release through RyR triggered basolateral Ca2+ entry or store‐operated Ca2+ entry (SOCE) mechanism and the subsequent Ca2+ entry via Na+/Ca2+ exchanger 1 (NCX1) were found to be critical in Na+‐glucose cotransporter‐mediated glucose absorption. Blocking RyR, SOCE and NCX1 inhibited glucose induced [Na+]cyt and [Ca2+]cyt in single IEC and protein expression and co‐localization of STIM1/Orai1, RyR1 and NCX1 were detected in IEC and jejunal mucosa.Conclusion and ImplicationsLuminal Ca2+ influx through Cav1.3 triggers the CICR through RyR1 to deplete the ER Ca2+, which induces the basolateral STIM1/Orai1‐mediated SOCE mechanism and the subsequent Ca2+ entry via NCX1 to regulate intestinal glucose uptake via Ca2+ signalling. Targeting these mechanisms in IEC may help to modulate blood glucose and sodium in the metabolic disease.

The Influence of Peptidases in Intestinal Brush Border Membranes on the Absorption of Oligopeptides from Whey Protein Hydrolysate: An Ex Vivo Study Using an Ussing Chamber

For many years, it was believed that only amino acids, dipeptides, and tripeptides could be absorbed and thus reach the bloodstream. Nowadays, the bioavailability of oligopeptides is also considered possible, leading to new research. This pilot study investigates the activity of brush border enzymes on undigested whey protein hydrolysate (WPH) and on simulated intestinal digested (ID) whey hydrolysate and the subsequent absorption of resultant peptides through the proximal jejunum of a 7-week old piglet setup in an Ussing chamber model. Amongst all samples taken, 884 oligopeptides were identified. The brush border peptidase activity was intense in the first 10 min of the experiment, producing several new peptides in the apical compartment. With respect to the ID substrate, 286 peptides were detected in the basolateral compartment after 120 min of enzyme activity, originating from β-lactoglobulin (60%) and β-casein (20%). Nevertheless, only 0.6 to 3.35% of any specific peptide could pass through the epithelial barrier and thus reach the basolateral compartment. This study demonstrates transepithelial jejunum absorption of whey oligopeptides in an ex vivo model. It also confirmed the proteolytic activity of brush border enzymes on these oligopeptides, giving birth to a myriad of new bioactive peptides available for absorption.

Modeling of fluid flow, carbohydrate digestion, and glucose absorption in human small intestine

The aim of this study was to develop a numerical model for simulating fluid flow, carbohydrate digestion, and glucose absorption in human small intestine. COMSOL Multiphysics® software was used to develop the numerical model. The intestinal geometry parameters, motility parameters, intestinal content properties, and digestion kinetics were obtained from the literature. The glucose absorption process was simulated by assuming that the intestinal tube is enclosed in an outer cylindrical tube with an intermediate diffusion wall. The properties of the intermediate diffusion wall were estimated by comparing numerical predictions with experimental results of in vitro digestion of 5 g glucose and 5 g maltodextrin in water-based food solutions. The jejunum numerical model with the intermediate diffusion wall of 2 mm thickness and the glucose diffusivity value of 5.25 × 10−9 m2/s, predicted the experimental cumulative jejunal glucose absorption values of 3.67 g (glucose feed) and 3.74 g (maltodextrin feed) with an average error of 0.07 g and 0.2 g, respectively.

Effect of the Source of Zinc on the Tissue Accumulation of Zinc and Jejunal Mucosal Zinc Transporter Expression in Holstein Dairy Calves.

Simple SummaryDiarrhea is the main cause of death in newborn calves and is associated with antibiotic use and economic loss for dairy farms. In this study, we evaluated the effects of different sources of the mineral zinc (zinc oxide (ZnO) and zinc methionine (Zn-Met)) on the growth, incidence of diarrhea, tissue zinc accumulation, gene expression of jejunal zinc transporters and serum concentrations of zinc-dependent proteins in newborn Holstein dairy calves. We found that Zn-Met supplementation promoted growth and reduced diarrhea from the second week after birth. It also increased the levels of zinc in the serum and liver, the level of the transporter protein ZIP4 in the jejunal mucosa, as well as the serum alkaline phosphatase and metallothionein concentrations compared to the control group. ZnO supplementation had similar but less marked effects to Zn-Met supplementation. These results suggest that Zn-Met supplementation may be an alternative to antibiotics for the treatment of newborn calf diarrhea.Zinc is considered to be an anti-diarrheal agent, and it may therefore reduce the incidence of diarrhea in young calves. In the present study, we aimed to compare the effect of zinc source on growth performance, the incidence of diarrhea, tissue zinc accumulation, the expression of zinc transporters, and the serum concentrations of zinc-dependent proteins in neonatal Holstein dairy calves. Eighteen male newborn Holstein dairy calves were fed milk and starter diet supplemented with or without 80 mg zinc/d in the form of Zn-Met or ZnO for 14 days, and were then euthanized. Zn-Met supplementation improved average daily gain and feed efficiency, and reduced the incidence of diarrhea, compared with control calves (p < 0.05). It also increased the serum and hepatic zinc concentrations and the mRNA expression of the ZIP4 transporter in the jejunal mucosa of the calves (p < 0.05). In addition, the serum alkaline phosphatase activity and metallothionein concentration were higher in Zn-Met-treated calves than in control calves (p < 0.05). ZnO supplementation had similar effects, but these did not reach significance. Thus, Zn-Met supplementation is an effective means of increasing tissue zinc accumulation and jejunal zinc absorption, and can be used as an anti-diarrheal strategy in neonatal calves.

Jejunal villus absorption and paracellular tight junction permeability are major routes for early intestinal uptake of food-grade TiO2 particles: an in vivo and ex vivo study in mice

Jejunal villus absorption and paracellular tight junction permeability are major routes for early intestinal uptake of food-grade TiO2 particles: an in vivo and ex vivo study in mice

Jejunal villus absorption and paracellular tight junction permeability are major routes for early intestinal uptake of food-grade TiO2 particles: an in vivo and ex vivo study in mice

BackgroundFood-grade TiO2 (E171 in the EU) is widely used as a coloring agent in foodstuffs, including sweets. Chronic dietary exposure raises concerns for human health due to proinflammatory properties and the ability to induce and promote preneoplastic lesions in the rodent gut. Characterization of intestinal TiO2 uptake is essential for assessing the health risk in humans. We studied in vivo the gut absorption kinetics of TiO2 in fasted mice orally given a single dose (40 mg/kg) to assess the ability of intestinal apical surfaces to absorb particles when available without entrapment in the bolus. The epithelial translocation pathways were also identified ex vivo using intestinal loops in anesthetized mice.ResultsThe absorption of TiO2 particles was analyzed in gut tissues by laser-reflective confocal microscopy and ICP-MS at 4 and 8 h following oral administration. A bimodal pattern was detected in the small intestine: TiO2 absorption peaked at 4 h in jejunal and ileal villi before returning to basal levels at 8 h, while being undetectable at 4 h but significantly present at 8 h in the jejunal Peyer’s patches (PP). Lower absorption occurred in the colon, while TiO2 particles were clearly detectable by confocal microscopy in the blood at 4 and 8 h after treatment. Ex vivo, jejunal loops were exposed to the food additive in the presence and absence of pharmacological inhibitors of paracellular tight junction (TJ) permeability or of transcellular (endocytic) passage. Thirty minutes after E171 addition, TiO2 absorption by the jejunal villi was decreased by 66% (p < 0.001 vs. control) in the presence of the paracellular permeability blocker triaminopyrimidine; the other inhibitors had no significant effect. Substantial absorption through a goblet cell (GC)-associated pathway, insensitive to TJ blockade, was also detected.ConclusionsAfter a single E171 dose in mice, early intestinal uptake of TiO2 particles mainly occurred through the villi of the small intestine, which, in contrast to the PP, represent the main absorption surface in the small intestine. A GC-associated passage and passive diffusion through paracellular TJ spaces between enterocytes appeared to be major absorption routes for transepithelial uptake of dietary TiO2.

Mitochondrial bioenergetics, uncoupling protein-2 activity, and reactive oxygen species production in the small intestine of a TNBS-induced colitis rat model.

Inflammatory bowel disease (IBD) is often associated with a decrease in energy-dependent nutrient uptake across the jejunum that serves as the main site for absorption in the small intestine. This association has prompted us to investigate the bioenergetics underlying the alterations in jejunal absorption in 2,4,6-trinitrobenzenesulfonic acid-induced colitis in rats. We have found that mitochondrial oxygen consumption did not change in state 2 and state 3 respirations but showed an increase in state 4 respiration indicating a decrease in the respiratory control ratio of jejunal mitochondria during the peak of inflammation. This decrease in the coupling state was found to be guanosine diphosphate-sensitive, hence, implicating the involvement of uncoupling protein-2 (UCP2). Furthermore, the study has reported that the production of reactive oxygen species (ROS), known to be activators of UCP2, correlated negatively with UCP2 activity. Thus, we suggest that ROS production in the jejunum might be activating UCP2 which has an antioxidant activity, and that uncoupling of the mitochondria decreases the efficiency of energy production, leading to a decrease in energy-dependent nutrient absorption. Hence, this study is the first to account for an involvement of energy production and a role for UCP2 in the absorptive abnormalities of the small intestine in animal models of colitis.