scholarly journals Dietary calcium decreases but short-chain fructo-oligosaccharides increase colonic permeability in rats

2010 ◽  
Vol 104 (12) ◽  
pp. 1780-1786 ◽  
Author(s):  
Marloes A. A. Schepens ◽  
Anneke Rijnierse ◽  
Arjan J. Schonewille ◽  
Carolien Vink ◽  
Robert-Jan M. Brummer ◽  
...  
Keyword(s):  
Gastrointestinal Tract ◽  
Intestinal Permeability ◽  
Control Diet ◽  
Short Chain ◽  
Gut Permeability ◽  
Colonic Tissue ◽  
Ussing Chambers ◽  
Small Intestinal ◽  
Gastrointestinal Permeability

An increased intestinal permeability is associated with several diseases. Nutrition can influence gut permeability. Previously, we showed that dietary Ca decreases whereas dietary short-chain fructo-oligosaccharides (scFOS) increase intestinal permeability in rats. However, it is unknown how and where in the gastrointestinal tract Ca and scFOS exert their effects. Rats were fed a Western low-Ca control diet, or a similar diet supplemented with either Ca or scFOS. Lactulose plus mannitol and Cr-EDTA were added to the diets to quantify small and total gastrointestinal permeability, respectively. Additionally, colonic tissue was mounted in Ussing chambers and exposed to faecal water of these rats. Dietary Ca immediately decreased urinary Cr-EDTA excretion by 24 % in Ca-fed rats compared with control rats. Dietary scFOS increased total Cr-EDTA permeability gradually with time, likely reflecting relatively slow gut microbiota adaptations, which finally resulted in a 30 % increase. The lactulose:mannitol ratio was 15 % higher for Ca-fed rats and 16 % lower for scFOS-fed rats compared with control rats. However, no dietary effect was present on individual urinary lactulose and mannitol excretion. The faecal waters did not influence colonic permeability in Ussing chambers. In conclusion, despite effects on the lactulose:mannitol ratio, individual lactulose values did not alter, indicating that diet did not influence small-intestinal permeability. Therefore, both nutrients affect permeability only in the colon: Ca decreases, while scFOS increase colonic permeability. As faecal water did not influence permeability in Ussing chambers, probably modulation of mucins and/or microbiota is important for the in vivo effects of dietary Ca and scFOS.

scholarly journals Exploring the role of the metabolite-sensing receptor GPR109a in diabetic nephropathy

2019 ◽  
Author(s):  
Matthew Snelson ◽  
Sih Min Tan ◽  
Gavin C. Higgins ◽  
Runa Lindblom ◽  
Melinda T. Coughlan
Keyword(s):  
Diabetic Nephropathy ◽  
Intestinal Permeability ◽  
Renal Injury ◽  
Resistant Starch ◽  
Control Diet ◽  
Critical Role ◽  
Intestinal Morphology ◽  
Gastrointestinal Permeability

AbstractAlterations in gut homeostasis may contribute to the progression of diabetic nephropathy. There has been recent attention on the renoprotective effects of metabolite-sensing receptors in chronic renal injury, including the G-protein-coupled-receptor (GPR)109a, which ligates the short chain fatty acid butyrate. However, the role of GPR109a in the development of diabetic nephropathy, a milieu of diminished microbiome-derived metabolites, has not yet been determined. This study aimed to assess the effects of insufficient GPR109a signalling via genetic deletion of GPR109a on the development of renal injury in diabetic nephropathy. Gpr109a−/− mice or their wildtype littermates (Gpr109a+/+) were rendered diabetic with streptozotocin (STZ). Mice received a control diet or an isocaloric high fiber diet (12.5% resistant starch) for 24 weeks and gastrointestinal permeability and renal injury were determined. Diabetes was associated with increased albuminuria, glomerulosclerosis and inflammation. In comparison, Gpr109a−/− mice with diabetes did not show an altered renal phenotype. Resistant starch supplementation did not afford protection from renal injury in diabetic nephropathy. Whilst diabetes was associated with alterations in intestinal morphology, intestinal permeability assessed in vivo using the FITC-dextran test was unaltered. GPR109a deletion did not worsen gastrointestinal permeability. Further, 12.5% resistant starch supplementation, at physiological concentrations, had no effect on intestinal permeability or morphology. These studies indicate that GPR109a does not play a critical role in intestinal homeostasis in a model of type 1 diabetes or in the development of diabetic nephropathy.

scholarly journals Exploring the role of the metabolite-sensing receptor GPR109a in diabetic nephropathy

2020 ◽  
Vol 318 (3) ◽  
pp. F835-F842
Author(s):  
Matthew Snelson ◽  
Sih Min Tan ◽  
Gavin C. Higgins ◽  
Runa S. J. Lindblom ◽  
Melinda T. Coughlan
Keyword(s):  
Diabetic Nephropathy ◽  
Intestinal Permeability ◽  
Renal Injury ◽  
Resistant Starch ◽  
Control Diet ◽  
Critical Role ◽  
Intestinal Morphology ◽  
Gastrointestinal Permeability

Alterations in gut homeostasis may contribute to the progression of diabetic nephropathy. There has been recent attention on the renoprotective effects of metabolite-sensing receptors in chronic renal injury, including the G protein-coupled receptor (GPR)109a, which ligates the short-chain fatty acid butyrate. However, the role of GPR109a in the development of diabetic nephropathy, a milieu of diminished microbiome-derived metabolites, has not yet been determined. The present study aimed to assess the effects of insufficient GPR109a signaling, via genetic deletion of GPR109a, on the development of renal injury in diabetic nephropathy. Gpr109a−/− mice or their wild-type littermates ( Gpr109a+/+) were rendered diabetic with streptozotocin. Mice received a control diet or an isocaloric high-fiber diet (12.5% resistant starch) for 24 wk, and gastrointestinal permeability and renal injury were determined. Diabetes was associated with increased albuminuria, glomerulosclerosis, and inflammation. In comparison, Gpr109a−/− mice with diabetes did not show an altered renal phenotype. Resistant starch supplementation did not afford protection from renal injury in diabetic nephropathy. While diabetes was associated with alterations in intestinal morphology, intestinal permeability assessed in vivo using the FITC-dextran test was unaltered. GPR109a deletion did not worsen gastrointestinal permeability. Furthermore, 12.5% resistant starch supplementation, at physiological concentrations, had no effect on intestinal permeability or morphology. The results of this study indicate that GPR109a does not play a critical role in intestinal homeostasis in a model of type 1 diabetes or in the development of diabetic nephropathy.

Novel telemetric system for extraluminal measurement of gastrointestinal motility

1976 ◽  
Vol 41 (3) ◽  
pp. 425-428 ◽  
Author(s):  
N. L. Shearin ◽  
C. J. Pfeiffer ◽  
S. Kilam
Keyword(s):  
Gastrointestinal Tract ◽  
Motor Function ◽  
Gastrointestinal Motility ◽  
Motility Pattern ◽  
Intravenous Injections ◽  
In Vivo Measurement ◽  
Meat Meal ◽  
Telemetric System ◽  
Small Intestinal

A frequency-modulated, telemetric system with a transducer sensitive to variation in distance between two points was developed and used to measure in vivo small intestinal motor function in unanesthetized dogs. The construction of the system and one application of it to the study of gastrointestinal motility is described. Data were recorded after fasting, 1 h after feeding a standardized meat meal, and after intravenous injections of pentagastrin. A significant increase in motility was seen after pentagastrin injections and feeding as compared to the motility pattern seen in a fasting animal, and the telemetric system was proven adequate for in vivo measurement of motility of the gastrointestinal tract.

Converging effects of a Bifidobacterium and Lactobacillus probiotic strain on mouse intestinal physiology

2014 ◽  
Vol 307 (2) ◽  
pp. G241-G247 ◽  
Author(s):  
Kevin W. Lomasney ◽  
John F. Cryan ◽  
Niall P. Hyland
Keyword(s):  
Ion Transport ◽  
Water Content ◽  
Short Circuit ◽  
Intestinal Transit ◽  
Current Response ◽  
Dependent Manner ◽  
Small Intestinal Transit ◽  
Ussing Chambers ◽  
Small Intestinal

Evidence has grown to support the efficacy of probiotics in the management of gastrointestinal disorders, many of which are associated with dysregulated fluid and electrolyte transport. A growing body of evidence now suggests that the host microbiota and probiotics can influence intestinal ion transport and that these effects often occur in a strain-dependent manner. In this study, we sought to investigate the effects of two therapeutically relevant organisms, Bifidobacterium infantis 35624 and Lactobacillus salivarius UCC118, on small intestinal transit, fecal output and water content, transepithelial resistance (TER), and colonic secretomotor function. Mice fed either strain displayed significantly reduced small intestinal transit in vivo, though neither strain influenced fecal pellet output or water content. Colon from mice fed both organisms displayed increased colonic TER, without a concomitant change in the gene expression of the tight junction proteins claudin 1 and occludin. However, L. salivarius UCC118 selectively inhibited neurally evoked ion secretion in tissues from animals fed this particular probiotic. Consistent with this finding, the neurotoxin tetrodotoxin (TTx) significantly inhibited the short-circuit current response induced by L. salivarius UCC118 following addition to colonic preparations in Ussing chambers. Responses to B. infantis 35624 also displayed sensitivity to TTx, although to a significantly lesser degree than L. salivarius UCC118. Both strains similarly inhibited cholinergic-induced ion transport after addition to Ussing chambers. Taken together, these data suggest that B. infantis 35624 and L. salivarius UCC118 may be indicated in disorders associated with increased small intestinal transit, and, in particular for L. salivarius UCC118, neurally mediated diarrhea.

Small intestinal efflux mediated by MRP2 and BCRP shifts sulfasalazine intestinal permeability from high to low, enabling its colonic targeting

2009 ◽  
Vol 297 (2) ◽  
pp. G371-G377 ◽  
Author(s):  
Arik Dahan ◽  
Gordon L. Amidon
Keyword(s):  
Intestinal Absorption ◽  
Intestinal Permeability ◽  
Oral Drug ◽  
Dependent Manner ◽  
Therapeutic Action ◽  
Cancer Resistance ◽  
High Permeability ◽  
Small Intestinal ◽  
Intestinal Efflux

Sulfasalazine is characterized by low intestinal absorption, which essentially enables its colonic targeting and therapeutic action. The mechanisms behind this low absorption have not yet been elucidated. The purpose of this study was to investigate the role of efflux transporters in the intestinal absorption of sulfasalazine as a potential mechanism for its low small-intestinal absorption and colonic targeting following oral administration. The effects of P-glycoprotein (P-gp), multidrug resistance-associated protein 2 (MRP2), and breast cancer resistance protein (BCRP) inhibitors on sulfasalazine bidirectional permeability were studied across Caco-2 cell monolayers, including dose-response analysis. Sulfasalazine in vivo permeability was then investigated in the rat jejunum by single-pass perfusion, in the presence vs. absence of inhibitors. Sulfasalazine exhibited 19-fold higher basolateral-to-apical (BL-AP) than apical-to-basolateral (AP-BL) Caco-2 permeability, indicative of net mucosal secretion. MRP2 inhibitors (MK-571 and indomethacin) and BCRP inhibitors [fumitremorgin C (FTC) and pantoprazole] significantly increased AP-BL and decreased BL-AP sulfasalazine Caco-2 transport in a concentration-dependent manner. No effect was observed with the P-gp inhibitors verapamil and quinidine. The IC50 values of the specific MRP2 and BCRP inhibitors MK-571 and FTC on sulfasalazine secretion were 21.5 and 2.0 μM, respectively. Simultaneous inhibition of MRP2 and BCRP completely abolished sulfasalazine Caco-2 efflux. Without inhibitors, sulfasalazine displayed low (vs. metoprolol) in vivo intestinal permeability in the rat model. MK-571 or FTC significantly increased sulfasalazine permeability, bringing it to the low-high permeability boundary. With both MK-571 and FTC present, sulfasalazine displayed high permeability. In conclusion, efflux transport mediated by MRP2 and BCRP, but not P-gp, shifts sulfasalazine permeability from high to low, thereby enabling its colonic targeting and therapeutic action. To our knowledge, this is the first demonstration of intestinal efflux acting in favor of oral drug delivery.

scholarly journals The Role of Intestinal Permeability in Gastrointestinal Disorders and Current Methods of Evaluation

2021 ◽  
Vol 8 ◽  
Author(s):  
Tim Vanuytsel ◽  
Jan Tack ◽  
Ricard Farre
Keyword(s):  
Intestinal Permeability ◽  
Barrier Function ◽  
Crucial Role ◽  
Intestinal Barrier Function ◽  
Current Evidence ◽  
Gastrointestinal Disorders ◽  
Fatty Acid Binding ◽  
Ussing Chambers

An increased intestinal permeability has been described in various gastrointestinal and non-gastrointestinal disorders. Nevertheless, the concept and definition of intestinal permeability is relatively broad and includes not only an altered paracellular route, regulated by tight junction proteins, but also the transcellular route involving membrane transporters and channels, and endocytic mechanisms. Paracellular intestinal permeability can be assessed in vivo by using different molecules (e.g., sugars, polyethylene glycols, 51Cr-EDTA) and ex vivo in Ussing chambers combining electrophysiology and probes of different molecular sizes. The latter is still the gold standard technique for assessing the epithelial barrier function, whereas in vivo techniques, including putative blood biomarkers such as intestinal fatty acid-binding protein and zonulin, are broadly used despite limitations. In the second part of the review, the current evidence of the role of impaired barrier function in the pathophysiology of selected gastrointestinal and liver diseases is discussed. Celiac disease is one of the conditions with the best evidence for impaired barrier function playing a crucial role with zonulin as its proposed regulator. Increased permeability is clearly present in inflammatory bowel disease, but the question of whether this is a primary event or a consequence of inflammation remains unsolved. The gut-liver axis with a crucial role in impaired intestinal barrier function is increasingly recognized in chronic alcoholic and metabolic liver disease. Finally, the current evidence does not support an important role for increased permeability in bile acid diarrhea.

Kinetic model of whole-body vanadium metabolism: studies in sheep

1986 ◽  
Vol 251 (2) ◽  
pp. R325-R332 ◽  
Author(s):  
B. W. Patterson ◽  
S. L. Hansard ◽  
C. B. Ammerman ◽  
P. R. Henry ◽  
L. A. Zech ◽  
...  
Keyword(s):  
Steady State ◽  
Gastrointestinal Tract ◽  
Kinetic Model ◽  
Rate Constants ◽  
Compartmental Model ◽  
Control Diet ◽  
Whole Body ◽  
Future Studies ◽  
Upper Gastrointestinal

A compartmental model for vanadium metabolism in sheep has been proposed. The model is consistent with data obtained from sheep fed a control diet (2.6 ppm vanadium) containing 0 or 200 ppm supplemental vanadium. Sheep were administered 48V dioxovanadium either orally or intravenously. Blood, feces, and urine radioactivity were monitored for 6 days postdosing. Several new insights regarding vanadium metabolism are suggested and tested against the data using the model. Some of these include significant absorption of 48V occurs from the upper gastrointestinal tract; an in vivo process is necessary in order for 48V dioxovanadium to be converted into a more biologically reactive species; at steady state the upper and lower gastrointestinal tracts contain at least 10- and 100-fold more mass of vanadium, respectively, than does blood. No statistically significant differences in transport rate constants were found between animals receiving 0 and 200 ppm supplemental dietary vanadium. The availability of a model will enable the refinement of future studies regarding vanadium metabolism in the ruminant.

Prolonged interferon-γ exposure decreases ion transport, NKCC1, and Na+-K+-ATPase expression in human intestinal xenografts in vivo

2004 ◽  
Vol 286 (1) ◽  
pp. G157-G165 ◽  
Author(s):  
Lone S. Bertelsen ◽  
Lars Eckmann ◽  
Kim E. Barrett
Keyword(s):  
Ion Transport ◽  
Prolonged Exposure ◽  
Intestinal Inflammation ◽  
Interferon Γ ◽  
Α Subunit ◽  
Ussing Chambers ◽  
Epithelial Cell Lines ◽  
Ifn Γ ◽  
Small Intestinal

IFN-γ is elevated in intestinal inflammation and alters barrier and transport functions in human colonic epithelial cell lines, but its effects on normal human small intestinal epithelium in vivo are poorly defined. We investigated effects of prolonged IFN-γ exposure on ion transport and expression of transporters by using human fetal small intestinal xenografts. Xenograft-bearing mice were injected with IFN-γ, and 24 h later xenografts were harvested and mounted in Ussing chambers. Baseline potential difference (PD) was not affected by IFN-γ treatment. However, conductance was enhanced and agonist-stimulated ion transport was decreased. IFN-γ also decreased expression of the Na+-K+-2Cl- cotransporter and the α-subunit of Na+-K+-ATPase compared with controls, whereas levels of the calcium-activated Cl- channel and CFTR were unaltered. Thus prolonged exposure to IFN-γ leads to decreased ion secretion due, in part, to decreased ion transporter levels. These findings demonstrate the implications of elevated IFN-γ levels in human small intestine and validate the human intestinal xenograft as a model to study chronic effects of physiologically relevant stimuli.

Effect of Water-Loading on the Performance of Polyethylene Glycol as a Marker of Small Intestinal Permeability

1995 ◽  
Vol 89 (3) ◽  
pp. 299-303 ◽  
Author(s):  
Tariq H. Iqbal ◽  
Mark A. Cox ◽  
Kenneth O. Lewis ◽  
Brian T. Cooper
Keyword(s):  
Polyethylene Glycol ◽  
Intestinal Permeability ◽  
Volume Of Distribution ◽  
Differential Rate ◽  
Water Loading ◽  
Collection Period ◽  
Small Intestinal ◽  
Renal Tubular ◽  
The Individual

1. Polyethylene glycol has been used extensively to measure small intestinal permeability in vivo. However, polyethylene glycol seems to traverse the intestinal mucosa in much greater quantities than sugar molecules of equivalent Mr. In addition, the recovery of the lowest Mr polymers of administered polyethylene glycol has been found to be both low and unreliable. 2. To compare the behaviour of a range of polyethylene glycol polymers with sugar probes in vivo, a combined polyethylene glycol/mannitol/lactulose probe was administered sequentially to healthy individuals in the fasted state and under conditions of water-loading. Timed hourly urine collections were made for 6 h. 3. Mannitol and lactulose recoveries were all within the normal range and were unaffected by coadministration of water. The lactulose/mannitol recovery ratios did not vary significantly over the 6 h collection period. In contrast, the recovery of total polyethylene glycol was significantly greater when subjects were water-loaded. Futhermore, proportionally greater quantities of polyethylene glycol Mr 370 than Mr 854 were recovered towards the end of the collection period than at the start. 4. Our results show that, in contrast to lactulose and mannitol, excretion of low—medium Mr polyethylene glycol polymers is highly dependent on coadministration of water. Futhermore, the differential rate of excretion of the low compared with the high Mr polyethylene glycol polymers suggests that the volume of distribution of the individual polymers may vary with Mr, and smaller polyethylene glycol molecules may undergo considerable renal tubular reabsorption.

scholarly journals Short-term adaptation of the ruminal epithelium involves abrupt changes in sodium and short-chain fatty acid transport

2014 ◽  
Vol 307 (7) ◽  
pp. R802-R816 ◽  
Author(s):  
Brittney L. Schurmann ◽  
Matthew E. Walpole ◽  
Pawel Górka ◽  
John C. H. Ching ◽  
Matthew E. Loewen ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Barrier Function ◽  
Short Chain Fatty Acid ◽  
Control Diet ◽  
Chain Fatty Acid ◽  
Short Chain ◽  
Fatty Acid Transport ◽  
Epithelial Surface ◽  
Ussing Chambers ◽  
Ruminal Epithelium

The objectives of this study were to determine the effect of an increase in diet fermentability on 1) the rate and extent to which short-chain fatty acid (SCFA) absorption pathways adapt relative to changes in Na+transport, 2) the epithelial surface area (SA), and 3) the barrier function of the bovine ruminal epithelium. Twenty-five Holstein steer calves were assigned to either the control diet (CON; 91.5% hay and 8.5% supplement) or a moderately fermentable diet (50% hay; 41.5% barley grain (G), and 8.5% supplement) fed for 3 (G3), 7 (G7), 14 (G14), or 21 days (G21). All calves were fed at 2.25% body weight at 0800. Calves were killed (at 1000), and ruminal tissue was collected to determine the rate and pathway of SCFA transport, Na+transport and barrier function in Ussing chambers. Tissue was also collected for SA measurement and gene expression. Mean reticular pH decreased from 6.90 for CON to 6.59 for G7 and then increased (quadratic P < 0.001). While effective SA of the ruminal epithelium was not affected ( P > 0.10) by dietary treatment, the net Na+flux increased by 125% within 7 days (quadratic P = 0.016). Total acetate and butyrate flux increased from CON to G21, where passive diffusion was the primary SCFA absorption pathway affected. Increased mannitol flux, tissue conductance, and tendencies for increased expression of IL-1β and TLR2 indicated reduced rumen epithelium barrier function. This study indicates that an increase in diet fermentability acutely increases Na+and SCFA absorption in the absence of increased SA, but reduces barrier function.

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