Sugar Absorption Test Research Articles

Early human milk feeding: Relationship to intestinal barrier maturation and postnatal growth.

Early exposure to mother's own milk (MOM) promotes intestinal barrier maturation in preterm infants. We hypothesized (1) donor human milk (DHM) supplementation reduces intestinal permeability (IP) similar to exclusive MOM and (2) early HM exposure and low IP at 7-10 days postnatal age (PNA) are associated with improved growth outcomes. IP was measured by the standard sugar absorption test (SAT) in infants <33 weeks gestation between 7-10 days PNA. Nutritional and anthropometric data were recorded. Postnatal growth failure (PNGF) was defined as a decrease in weight z-score >1 from birth to discharge to home. Of 158 preterm infants, the mean (SD) gestational age was 29.9(2.3) weeks and birthweight 1388(424) g. Diet prior to SAT was exclusive MOM [N = 55(35%)], DHM ± MOM [N = 52(33%)], or preterm formula±MOM [N = 51(32%)]. The mean Lactulose(La)/Rhamnose(Rh) ratio was lower in the exclusive MOM [0.06(0.07)] and DBM ± MOM [0.05(0.07)] groups compared to the preterm formula±MOM group [0.11(0.11)], p < 0.01). Cumulative intake >150 ml/kg MOM ± DHM, but not preterm formula within 7-10 days PNA was associated with early intestinal barrier maturation. Low IP was not associated with lower risk of PNGF at discharge. Low IP is associated with cumulative intake of MOM alone or supplemented with DHM > 150 ml/kg within 7-10 days PNA. Clinicaltrials.gov NCT01756040 ; web link to study on registry: https://clinicaltrials.gov/study/NCT01756040 . Key message Early intestinal barrier maturation is associated with cumulative intake of exclusive MOM alone or supplemented with DHM > 150 ml/kg within 7-10 days after birth, but is not associated with lower risk of PNGF at time of discharge. What it adds to existing literature? This observational study is the first study to demonstrate that supplemental DHM promotes intestinal barrier maturation similar to MOM alone. What is the impact? The findings underscore the importance of early introduction of human milk feeds as MOM or MOM supplemented with DHM in sufficient volume to promote early intestinal barrier maturation.

Dietary milk phospholipids increase body fat and modulate gut permeability, systemic inflammation, and lipid metabolism in mice

The study aimed at how dietary milk polar lipids affect gut permeability, systemic inflammation, and lipid metabolism during diet-induced obesity (DIO). C57BL/6J mice (n = 6x3) were fed diets with 34% fat as energy for 15 weeks: (1) modified AIN-93G diet (CO); (2) CO with milk gangliosides (GG); (3) CO with milk phospholipids (MPL). Gut permeability was assessed by FITC-dextran and sugar absorption tests. Intestinal tight junction proteins were evaluated by Western blot. Plasma cytokines were measured by immunoassay. Body composition was assessed by magnetic resonance imaging. Tissue lipid profiles were obtained by thin layer chromatography. Hepatic expression of genes associated with lipid metabolism was assessed by RT-qPCR. MPL increased the efficiency of converting food into body fat and facilitated body fat accumulation compared with CO. MPL and GG did not affect fasting glucose or HOMA-IR during DIO. MPL increased while GG decreased plasma TG compared with CO. MPL decreased phospholipids subclasses in the muscle while increased those in the liver compared with CO. GG and MPL had little effect on hepatic expression of genes associated with lipid metabolism. Compared with CO, MPL decreased polar lipids content in colon mucosa. Small intestinal permeability decreased while colon permeability increased and then recovered during the feeding period. High-fat feeding increased plasma endotoxin after DIO but did not affect plasma cytokines. MPL and GG did not affect plasma endotoxin, adipokines and inflammatory cytokines. After the establishment of obesity, MPL increased gut permeability to large molecules but decreased intestinal absorption of small molecules while GG tended to have the opposite effects. MPL and GG decreased mannitol and sucralose excretions, which peaked at d 45 in the CO group. MPL decreased occludin in jejunum mucosa compared with CO. GG and MPL did not affect zonula occludens-1 in gut mucosa. In conclusion, during DIO, milk GG decreased gut permeability, and had little effect on systemic inflammation and lipid metabolism; MPL facilitated body fat accumulation, decreased gut permeability, did not affect systemic inflammation.

A Rapid and Reliable Spectrofluorimetric Method to Measure the Urinary Lactulose/Mannitol Ratio for Dysbiosis Assessment.

Gut microbiota plays a crucial role in human health homeostasis, and the result of its alteration, known as dysbiosis, leads to several pathologies (e.g., inflammatory bowel disease, metabolic syndrome, and Crohn's disease). Traditional methods used to assess dysbiosis include the dual sugar absorption test and the urinary lactulose/mannitol ratio (LMR) measurement using mass spectrometry. Despite its precision, this approach is costly and requires specialized equipment. Hence, we developed a rapid and reliable spectrofluorimetric method for measuring LMR in urine, offering a more accessible alternative. This spectrofluorimetric assay quantifies the fluorescence of nicotinamide adenine dinucleotide (NADH) and nicotinamide adenine dinucleotide phosphate (NADPH) produced during the enzymatic oxidation of mannitol and lactulose, respectively. The assay requires 100 µL of urine samples and detects LMR values lower (eubiosis) and higher (dysbiosis) than 0.05, ultimately being amenable to high-throughput screening and automatization, making it practical for clinical and research settings. A validation of the method demonstrated its high precision, accuracy, and robustness. Additionally, this study confirmed analyte stability under various storage conditions, ensuring reliable results even with delayed analysis. Overall, this spectrofluorimetric technique reduces costs, time, and the environmental impact associated with traditional mass spectrometry methods, making it a viable option for widespread use in the assessment of dysbiosis.

90 Evaluating water- and feed-based arginine supplementation on newly weaned pig growth and gastrointestinal health

Abstract The objective of this experiment was to assess the influence of arginine (Arg) supplementation in water and/or feed on the growth performance and gastrointestinal health of newly weaned pigs. Pigs (n = 240; PIC 337 Χ 1050, Genus, Henderson, TN) were randomly allocated into 80 mixed-sex test pens and subjected to a 2 Χ 4 factorial design, with two levels of Arg supplementation in water (0% or 8% stock, dosed through a 1:128 proportioner) for the first phase (d 0-7), and four dietary arginine levels (0.85, 0.95, 1.05, and 1.15 standardized ileal digestible (SID) Arg to Lysine (Lys) ratios for the first two phases (d 0-7 and 7-21). All treatments were provided a common diet (0.96 SID Arg:Lys) for the last phase d 21- 42. One pig per pen underwent a dual sugar absorption test of lactulose at 500 mg/kg and mannitol at 50 mg/kg of body weight (BW) via gastric tube on d 7 and 21, with blood plasma collected 4 h post-administration. The pig tested on d 7 was subsequently euthanized for intestinal tissue collection. Pen growth performance and feed disappearance were evaluated for 3 phases; d 0-7, 7-21, and 21-42. The statistical analysis utilized generalized linear mixed model methods (SAS 9.4, Cary, NC) with the main effects of SID Arg:Lys in the feed and Arg level within the water, and the interaction between the two. Pen was the experimental unit. Orthogonal contrasts were tested for the linear and quadratic effects of the diet. Growth performance during the 1st period exhibited variability, reflected by negative gain to feed ratio (G:F), caused by health challenges of Rotavirus A. Consequently, data were analyzed separately for each phase. Increasing dietary SID Arg:Lys caused a significant linear effect (improvement; P = 0.04) on final BW (18.47 and 21.90 kg, for 0.85 and 1.15 SID Arg:Lys, respectively). However, discernible differences between dietary treatments were not observed (P &amp;gt; 0.1). Similarly, a trend (P = 0.09) suggested a linear impact of dietary SID Arg:Lys on average daily gain during the third phase (d 21-42). In terms of intestinal absorption and morphology, Arg supplementation, whether through water or diet, had no effect on lactulose and mannitol absorption on both d 7 and d 21, nor did it impact villous height, crypt depth, or the villi:crypt ratio in ileum tissues collected on d 7 post-weaning. In conclusion, dietary supplementation with Arg increased final BW but had no clear impacts on intestinal health within the variables measured, potentially impacted by the rotavirus diagnosis in the first week post wean.

PSIII-4 Evaluating the variability of the dual sugar absorption test as a measure of intestinal permeability in pigs

Abstract The intestinal barrier of pigs can be compromised by many factors including health challenges, off-feed events, and environmental stressors. If dysregulated barrier function is caught early, proper treatment can be initiated to potentially prevent more severe complications to overall health. However, there are few procedures to measure intestinal function in pigs that are both validated, sensitive, and minimally invasive. In this research, the dual sugar test using lactulose and mannitol was conducted on a total of 534 pigs of varying age, sex, body weight (BW), and health status. Each pig received the same oral dose of 500 mg/kg body weight lactulose and 50 mg/kg BW mannitol, and blood was collected either 60 or 240 min following the dose. Plasma concentrations of lactulose and mannitol were quantified by high performance liquid chromatography using validated methods. The ratio of lactulose to mannitol absorption (L:M) served as the indicator of barrier function such that a larger L:M ratio was indicative of greater intestinal permeability. In these pigs, L:M ratios ranged from 0 to 6.96. The median L:M ratio was 0.41 while the average was 0.70, indicating that the distribution of the data was right skewed, influenced by 21.0% of pigs exhibiting a L:M of 0. Collecting blood sooner after oral gavage yielded better detectability as only 2.71% of L:M in pigs from the 60 min group was 0 compared with 43.5% from the 240 min group. Ostensibly, an L:M ratio of 0 is biologically relevant, but interpretation of such values is challenging both from statistical and biological perspectives. Intestinal barrier permeability, absorption kinetics between pigs, and delivery efficiency of the L:M solution may all affect lactulose absorption yielding a ratio of 0. In general, the data werewere highly variable, with a standard deviation of 0.95, so a regression analysis was performed to determine which factors may be influencing this variation. Neither a forward nor a backward elimination model determined any of the five explanatory variables (i.e., BW, timing of blood collection, health status, age, or sex) to be significant. Additional correlational analyses further confirmed that there were no significant interactions. Overall, it appears that these factors do not help to explain the variability in the L:M ratio. Further investigation is warranted to validate this process and understand the source and impact of L:M ratios equaling 0.

A novel approach to the dual sugar test for the assessment of intestinal epithelium permeability in response to exertional heat stress and nutritional intervention

An acute increase in intestinal epithelium permeability is induced by prolonged exertion in the heat, resulting in the translocation of pathogenic bacteria and endotoxins from the lumen into the circulation, causing a systemic inflammatory response and debilitating symptoms(1). Acute exercise-induced gastrointestinal syndrome mimics chronic health conditions with which an impaired intestinal barrier function is associated, including coeliac disease, inflammatory bowel disease, diabetes, Alzheimer’s and liver diseases(2). Intestinal epithelium permeability is typically assessed using a dual sugar absorption test, by administering a drink containing non-metabolisable sugars (e.g. lactulose [L] and L-rhamnose [R]) that can enter the circulation by paracellular translocation when the epithelium is compromised, and are subsequently excreted and measured cumulatively in the urine(3). We aimed to demonstrate that our recently developed ion chromatography protocol(4) can be used to accurately quantify L/R ratio in the plasma of participants exercising in hot ambient conditions and to determine the impact of nutritional intervention on intestinal epithelium permeability. Further, we hypothesised that measuring L/R in plasma collected at intervals during the post-exercise recovery period would reveal more information about intestinal permeability compared to previously published cumulative urine L/R data(3). Endurance-trained participants completed a set of randomised crossover studies, consisting of 2 h running at 60% V˙O2max in temperate, warm and hot ambient conditions (n = 8) and/or in the heat while consuming water, carbohydrate or protein (n = 9). The dual sugar solution was ingested at 90 min of exercise and blood was sampled at 0, 1, 2 and 4 h post-exercise. Plasma sugars were quantified by high-performance anion exchange chromatography with pulsed amperometric detection (HPAEC-PAD) and L/R ratios were compared by two-way repeated measures ANOVA with Tukey’s multiple comparisons. Plasma L/R increased immediately post-exercise in the heat (0.15 ± 0.11) compared with temperate (0.06 ± 0.04, p&lt;0.001) and warm (0.09 ± 0.08, p&lt;0.01) conditions, while consuming glucose before and during exercise alleviated this (0.02 ± 0.02, p&lt;0.001), and this novel information was otherwise missed when measuring urine L/R. Consuming glucose or whey protein hydrolysate during exercise attenuated intestinal permeability from exertional heat stress throughout recovery, with the mean plasma L/R over 4 h reduced from 0.11 ± 0.05 to 0.04 ± 0.03 (p&lt;0.001) and 0.06 ± 0.04 (p&lt;0.01) with glucose and protein, respectively. We recommend using the dual sugar test with quantification of plasma sugars at intervals by HPAEC-PAD to maximise intestinal permeability data collection in exercise gastroenterology research and beyond, as this gives additional acute response information compared to urinary measurements. Our approach can be employed to investigate and develop personalised nutrition strategies that prevent intestinal hyperpermeability during exertional heat stress. This has implications for athlete performance and safety, and can also build upon occupational health and safety practices and inform chronic disease management.

Impact of increasing dietary standardized ileal digestible arginine to lysine ratio from 0.85 to 1.15 and water-based arginine supplementation on growth performance and gut integrity of weaned pigs.

The objective of this experiment was to assess the influence of arginine (Arg) supplementation in water and/or feed on the growth performance and gastrointestinal health of newly weaned pigs. Two hundred and forty pigs (5.06kg; PIC, Hendersonville, TN) were randomly allocated into 80 mixed-sex pens (3 pigs/pen) and subjected to a 2 × 4 factorial design. Two levels of Arg were supplemented in water (0% or 8% stock, dosed through a 1:128 proportioner) for the first phase (days 0 to 7), and four dietary arginine levels (0.85, 0.95, 1.05, and 1.15) standardized ileal digestible (SID) Arg to Lysine (Lys) ratios for the first two phases (days 0 to 7 and 7 to 21). All treatments were provided a common diet (0.96 SID Arg:Lys) for the last phase days 21 to 42. One pig per pen underwent a dual sugar absorption test of lactulose at 500mg/kg and mannitol at 50mg/kg of body weight (BW) via gastric tube on days 7 and 21 postweaning, with blood plasma collected 4h later. The pig tested on day 7 was subsequently euthanized for intestinal tissue collection. Pen growth performance and feed disappearance were evaluated for 3 phases: days 0 to 7, 7 to 21, and 21 to 42 postweaning. The statistical analysis used linear models to examine the effects of SID Arg:Lys in the feed, Arg level in water, and their interactions, with pen as the experimental unit. Orthogonal contrasts were used to test the linear and quadratic effects of increasing SID Arg:Lys in the diet. Growth performance during the first period exhibited variability, reflected by negative gain-to-feed (G:F) ratios, caused by the enteric health challenge. Consequently, data were analyzed separately for each phase. Increasing dietary SID Arg:Lys caused a linear improvement (P = 0.04) in final BW (18.47 and 21.90kg, for 0.85 and 1.15 SID Arg:Lys, respectively). A trend (P = 0.09) suggested a linear impact of dietary SID Arg:Lys on average daily gain during days 21 to 42. Arg supplementation, whether administered through water or diet, did not affect lactulose and mannitol absorption on both days 7 and 21, nor did it alter histological measurements in the collected ileum tissues on day 7 postweaning. In conclusion, increasing dietary SID Arg:Lys increased final BW but had no clear impacts on intestinal health within the parameters measured, potentially impacted by the rotavirus diagnosis in the first week post-wean.

First-in-Human Assessment of Gut Permeability in Crohn’s Disease Patients Using Fluorophore Technology

Background and AimsThe dual sugar absorption test (DSAT) as a classic measure of human intestinal permeability has limited clinical utility due to lengthy and cumbersome urine collection, assay variability, and long turnaround. We aimed to determine if the orally administered fluorophore MB-102 (relmapirazin) (MW=372) compares to lactulose (L) (MW=342) and rhamnose (R) (MW=164)-based DSAT as a measure of gut permeability in people with a spectrum of permeability including those with Crohn’s disease (CD). MethodsWe performed a single center, randomized, open label, crossover study comparing orally administered MB-102 (1.5 or 3.0 mg/kg) to L (1000 mg) and R (200 mg). Adults with active small bowel CD on magnetic resonance enterography (cases) and healthy adults (controls) were randomized to receive either MB-102 or L and R on study day 1, and the other tracer 3-7 days later. Urine was collected at baseline and 1, 2, 4, 6, 8, 10, and 12 hours after tracer ingestion to calculate the cumulative urinary percent excretion of MB-102 and L and R. ResultsNine cases and 10 controls completed the study without serious adverse events. Urinary recovery of administered MB-102 correlated with recovery of lactulose (r-squared = 0.83) for all participants. MB-102 urine recovery also tracked with the L:R ratio urine recovery (r-squared=0.57). In controls, the percentages of L and MB-102 recovered were similar within a narrow range unlike in CD patients. ConclusionsThis first-in-human study of an orally administered fluorophore to quantify gastrointestinal permeability in adults with CD demonstrates that MB-102 is well tolerated, and its recovery in urine mirrors that of percent L and the L:R ratio.

A corn-fermented protein ingredient can be included in early nursey diets without compromising pig growth performance and health status.

In nursery diets, ingredients with high protein content and highly digestible nutrients, such as corn-fermented protein product with added yeast mass (GDDY), can be included as an alternative to common protein sources. This study investigated the dietary inclusion of GDDY as an alternative protein source on growth performance and intestinal health of weaned pigs. A total of 594 weaned pigs (5.7 ± 0.9kg; 18.5 days of age) were allotted to 36 pens in a randomized incomplete block design. Pens were assigned to one of 4 dietary treatments: CON: a common nursery feeding program; SBM75: CON diet replacing 75% of soybean meal (SBM) with GDDY; FM/ESBM: CON diet without fish meal (FM) and enzyme-treated SBM (ESBM) + GDDY; GDDY50: CON diet replacing 50% of SBM, FM, and ESBM with GDDY. Experimental diets were formulated to meet nutrient requirements of nursery pigs and provided in meal form through four phases during the nursery period. Pig growth performance was assessed on days 7, 14, 21, 28, 42, and 53. Pen fecal score was assessed daily from days 0 to 14, and 3 times per week from days 15 to 35. Intestinal health was assessed based on plasma immunoglobulin A (IgA) concentration and the differential sugar absorption test. The total tract digestibility of dry matter (DM), crude protein (CP), gross energy (GE), and phosphorus was also evaluated. From days 0 to 7 and days 7 to 14, dietary treatment had no effect (P > 0.05) on BW, ADG, and ADFI. For the rest of the experimental period, ADG and ADFI were greater (P < 0.05) in pigs fed CON in comparison with those fed SBM75 and GDDY50 and did not differ from pigs fed FM/ESBM. Pigs fed GDDY50 tended (P = 0.082) to have greater serum IgA concentration on day 20 when compared with SBM75 and FM/ESBM pigs. There were no differences among dietary treatments for DM, CP, and GE digestibility. Phosphorus digestibility was higher in FM/ESBM (P < 0.05) compared with SBM75 and GDDY50. These results supported the hypothesis that GDDY can be incorporated in nursery pig diets during the first couple weeks after weaning without affecting growth performance. However, in the late nursery period, inclusion levels starting at 14% can compromise performance.

Plasma measurements of the dual sugar test reveal carbohydrate immediately alleviates intestinal permeability caused by exertional heat stress.

The aim of this set of randomised cross-over studies was to determine the impact of progressive heat exposure and carbohydrate or protein feeding during exertional stress on small intestine permeability using a dual sugar test. In our previous work, and typically in the field, recovery of lactulose and l-rhamnose is measured cumulatively in urine. This follow-up study exploits our novel high-performance anion exchange chromatography with pulsed amperometric detection (HPAEC-PAD) protocol to accurately quantify the sugars in plasma. Endurance-trained participants completed experimental trial A (ET-A; n=8), consisting of 2h running at 60% in temperate, warm and hot ambient conditions, and/or experimental trial B (ET-B; n=9), consisting of 2h running at 60% in the heat while consuming water, carbohydrate or protein. Blood samples were collected and plasma lactulose (L) and l-rhamnose (R) appearance, after dual sugar solution ingestion at 90min of exercise, was quantified by HPAEC-PAD to measure plasma L/R and reveal new information about intestinal permeability immediately post-exercise and during recovery. In ET-A, plasma L/R increased immediately post-exercise in hot compared with temperate and warm conditions, while, in ET-B, carbohydrate alleviated this, and this information was otherwise missed when measuring urine L/R. Consuming carbohydrate or protein before and during exercise attenuated small intestine permeability throughout recovery from exertional heat stress. We recommend using the dual sugar test with quantification of plasma sugars by HPAEC-PAD at intervals to maximise intestinal permeability data collection in exercise gastroenterology research, as this gives additional information compared to urinary measurements. KEY POINTS: Intestinal permeability is typically assessed using a dual sugar test, by administering a drink containing non-metabolisable sugars (e.g. lactulose (L) and l-rhamnose (R)) that can enter the circulation by paracellular translocation when the epithelium is compromised, and are subsequently measured in urine. We demonstrate that our recently developed ion chromatography protocol can be used to accurately quantify the L/R ratio in plasma, and that measuring L/R in plasma collected at intervals during the post-exercise recovery period reveals novel acute response information compared to measuring 5-h cumulative urine L/R. We confirm that exercising in hot ambient conditions increases intestinal epithelial permeability immediately after exercise, while consuming carbohydrate or protein immediately before and during exercise attenuates this. We recommend using our dual sugar absorption test protocol to maximise intestinal epithelial permeability data collection in exercise gastroenterology research and beyond.

Performance and gut permeability of post-weaned piglets are influenced by different sources of lignocellulose fiber

Antibiotics and ZnO as antimicrobial agents in post-weaning diets can improve growth performance of nursery piglets. However, this practice can lead to antibiotic resistance and contribute to zinc pollution to the environment. Therefore, the aim of this study was to evaluate the effect of replacing AGP (antibiotic as growth promotor) with a lignocellulose or an eubiotic lignocellulose associated with different inclusion rates of ZnO in post-weaning diets on the piglet's growth performance, intestinal permeability, diarrhea score, Escherichia coli excretion and concentration, Zn and Cu fecal excretion. A total of 90 piglets weaned at 25 d of age (7.84 ± 1.71 kg) were distributed in a randomized block design and were assigned to 5 treatments: a commercial control diet, T1 (tiamulin as AGP with high dose of ZnO); T2 (lignocellulose with high dose of ZnO); T3 (eubiotic lignocellulose with high dose of ZnO); T4 (lignocellulose with low dose of ZnO); T5 (eubiotic lignocellulose with low dose of ZnO), with 6 replicates and 3 piglets per pen. The nutritional program was divided into 4 phases (phase 1: 25 to 32 d; phase 2: 33 to 39 d; phase 3: 40 to 53 d; phase 4: 54 to 67 d). The overall nursery voluntary feed intake was affected by the treatments (P < 0.001), whereas T5 and T1 showed the highest intakes followed by T2, T4, T3. Still, the treatments did not influence the final weight of the piglets. There were differences (P < 0.05) between the phases for the sugar absorption test (SAT). The observed SAT values in the second phase (60 d of age) were lower compared to the first phase (1 wk post-weaning). In addition, pigs fed low doses of ZnO in the diets showed lower (P < 0.05) fecal Zn and Cu excretions. In conclusion, the use of eubiotic lignocellulose fiber in the diets for piglets in the nursery phase can be a viable strategy to allow the withdrawal of tiamulin as an AGP and reduce the use of dietary ZnO without affecting negatively on the growth performance of the piglets, as well as reducing the fecal excretion into the environment. Nevertheless, one must consider the possibility that there will be an increased usage of injectable medication.

Analysis of PFAS in Locally Acquired Food Containers

The measurement of intestinal permeability is important for diagnoses of diseases of the gastrointestinal tract, such as Crohn’s disease. The gold standard for measurement of intestinal permeability is the dual sugar absorption test, which measures the urinary or blood concentrations of two orally administered sugars, a monosaccharide and a disaccharide, over a period of time. The lining of the small intestine allows monosaccharides to cross into the bloodstream, but the larger disaccharide is not permitted to cross the intestine unless the barrier is compromised. The permeability of the lining is measured by a ratio between select monosaccharides and disaccharides, and this indicates the overall status of the small intestine. In order to study the effects of resistance exercise on intestinal permeability in human subjects, we developed a liquid chromatography tandem mass spectrometry (LC–MS/MS) method for the analysis of saccharides in blood plasma. The analytes included rhamnose, a monosaccharide not commonly found in food, and lactulose, a disaccharide. A trisaccharide, raffinose, was used as an internal standard. The method was robust, and had consistent reliability.

Increased Intestinal Permeability and Stool Zonulin, Calprotectin and Beta-Defensin-2 Concentrations in Allogenic Hematopoietic Cell Transplantation Recipients.

Significant progress has been made in understanding the connection between intestinal barrier function and allogenic hematopoietic cell transplantation (allo-HCT) recipients' outcomes. The purpose of this study was to further evaluate gut barrier permeability and other potential intestinal barrier disruption markers in the allo-HCT setting. Fifty-one patients were enrolled in the study. Intestinal permeability was assessed with the sugar absorption test and faecal concentrations of the zonulin, calprotectin and beta-defensin-2 levels in the peri-transplantation period. Most patients undergoing allo-HCT in our department had a disrupted intestinal barrier at the baseline, which was associated with older age and higher Hematopoietic Cell Transplantation-specific Comorbidity Index (HCT-CI). Regardless of this, we observed a further increase in gut barrier permeability after allo-HCT in most patients. However, there was no association between permeability assay and other markers (zonulin, calprotectin and beta-defensin-2). Patients with acute GVHD had significantly higher median calprotectin concentrations after allo-HCT compared with the patients without this complication. Our findings indicate that gut barrier damage develops prior to allo-HCT with progression after the procedure and precedes further complications, but did not prove other markers to be useful surrogates of intestinal permeability.

PSXIII-B-7 Effect of Replacing soy Protein Concentrate with Corn Fermented Protein on Growth Performance and gut Integrity of Weaned Pigs

Abstract NexPRO™, a corn fermented protein (CFP) derived from the dry-mill bioethanol production process, has demonstrated potential as a high-quality protein ingredient in weaned pig diets. Therefore, the objective of this study was to determine the effects of increasing dietary inclusion of CFP to replace soy protein concentrate (SPC) in the diet on weight gain, feed intake, feed efficiency and gut integrity of weaned pigs in a large-scale system. A total of 1144 pigs were distributed evenly into 44 pens (13 barrows and 13 gilts/pen; initial BW 6.0±0.1 kg) with 286 pigs assigned per treatment and 11 replications. The four treatments were designed as a titration of CFP inclusion at 0%, 4%, 8% and 12% in Phase 1 (3.6 kg/hd budget) and 0%, 2%, 4% and 6% in Phase 2 (5.5 kg/hd budget) replacing SPC. Pigs were fed a common diet through Phase 3. To determine gut integrity, a differential sugar absorption test (DSAT) administered a 5% lactulose and 5% mannitol solution on the tenth day to representative pigs consuming the 0% and 12% CFP diets. Urine was collected to measure differences in sugar ratios to access gut permeability. Average daily gain responded similarly for the 0%, 4% and 8% CFP diets during Phase 1, however greater than 12% (P&amp;lt; 0.01; 0.15 vs. 0.11 kg/d). Pigs fed diets with 4% and 8% CFP in Phase 1 had a greater ADFI than pigs fed 12% CFP (0.19 vs. 0.17 kg/d; P˂0.01); 0% diets were intermediate. At the end of Phase 2, pigs fed 0%, 2%, and 4% CFP diets had greater (P˂0.01) ADFI than pigs fed diets with 6% CFP (0.60 vs. 0.44 kg/d), but lower (P&amp;lt; 0.01) G:F (0.62 vs. 0.78). No observed differences were measured between treatments for gut permeability. Due to similar responses in performance, CFP can replace soy protein concentrate in nursery diets.

The effect of sex, menstrual cycle phase and oral contraceptive use on intestinal permeability and ex-vivo monocyte TNFα release following treatment with lipopolysaccharide and hyperthermia

PurposeInvestigate the impact of sex, menstrual cycle phase and oral contraceptive use on intestinal permeability and ex-vivo tumour necrosis factor alpha (TNFα) release following treatment with lipopolysaccharide (LPS) and hyperthermia. MethodsTwenty-seven participants (9 men, 9 eumenorrheic women (MC) and 9 women taking an oral contraceptive pill (OC)) completed three trials. Men were tested on 3 occasions over 6 weeks; MC during early-follicular, ovulation, and mid-luteal phases; OC during the pill and pill-free phase. Intestinal permeability was assessed following a 4-hour dual sugar absorption test (lactulose: rhamnose). Venous blood was collected each trial and stimulated with 100 μg·mL−1 LPS before incubation at 37 °C and 40 °C and analysed for TNFα via ELISA. ResultsL:R ratio was higher in OC than MC (+0.003, p = 0.061) and men (+0.005, p = 0.007). Men had higher TNFα responses than both MC (+53 %, p = 0.004) and OC (+61 %, p = 0.003). TNFα release was greater at 40 °C than 37 °C (+23 %, p < 0.001). ConclusionsMen present with lower resting intestinal barrier permeability relative to women regardless of OC use and displayed greater monocyte TNFα release following whole blood treatment with LPS and hyperthermia. Oral contraceptive users had highest intestinal permeability however, neither permeability or TNFα release were impacted by the pill cycle. Although no statistical effect was seen in the menstrual cycle, intestinal permeability and TNFα release were more variable across the phases.

A Simple, Robust, and Convenient HPLC Assay for Urinary Lactulose and Mannitol in the Dual Sugar Absorption Test.

Background: Heterogeneous laborious analytical methodologies for the determination of urinary lactulose and mannitol limit their utility in intestinal permeability testing. Methods: We developed an assay using a Shimadzu HPLC system, an Aminex HPX87C column, and refractive index detection. The test was calibrated using a series of dilutions from standard stock solutions of lactulose and mannitol ‘spiked’ into urine samples. The utility to quantify urinary excretion during the dual sugar absorption test over 6 h was also determined. Results: Lactulose and mannitol were eluted isocratically at 5.7 and 10.1 min, respectively, with water as a mobile phase at a flow rate of 0.3 mL min−1, 858 psi, 60 °C. The calibration curves for both sugars were linear up to 500 µg mL−1 with a limit of detection in standard solutions at 4 µg mL−1 and in ‘spiked’ urine samples at 15 µg mL−1. The intra-assay and inter-assay CVs were between 2.0–5.1% and 2.0–5.1% for lactulose and 2.5–4.4% and 2.8–3.9% for mannitol. The urinary profiles of the 6 h absorption of lactulose and mannitol showed similar peak-retention times to standard solutions and were well-resolved at 5.9 and 10.4 min, respectively. Conclusions: The assay was easy to automate, using commonly available equipment and convenient requiring no prior laborious sample derivatization. The simplicity, reproducibility, and robustness of this assay facilitates its use in routine clinical settings for the quantification of intestinal permeability.

Rhamnose Is Superior to Mannitol as a Monosaccharide in the Dual Sugar Absorption Test: A Prospective Randomized Study in Children With Treatment-Naïve Celiac Disease

Background and AimWe sought to correlate two different measures of gut permeability [lactulose:mannitol (L:M) and lactulose:rhamnose (L:R)] to the severity of duodenal histopathology in children with and without elevated antibodies to tissue transglutaminase (tTG). A secondary objective was to correlate gut permeability with celiac disease (CD) serology and indices of inflammation and bacterial product translocation.MethodsWe prospectively randomized children undergoing endoscopy with abnormal (n = 54) and normal (n = 10) concentrations of circulating antibodies to tTG, to either L:M or L:R. Biopsies underwent modified Marsh scoring to measure mucosal injury. Circulating anticore Escherichia coli lipopolysaccharide (LPS) IgG, α-1 acid glycoprotein, LPS-binding protein, and C-reactive protein concentrations were measured by enzyme immunoassays.ResultsOf the 54 cases with positive celiac serology, 31 and 69% had modified Marsh 0/1 scores or ≥3a, respectively. Circulating tTG IgA correlated with the modified Marsh score (p = 0.03). L:R, but not L:M or percent L excreted, differed according to modified Marsh scores (p = 0.01). There was no significant association between any systemic marker of inflammation or gut injury, and modified Marsh scores. Concerningly, most participants had evidence of urinary M before the challenge sugar was administered.ConclusionsL:R, but not L:M, is associated with modified Marsh scores in children undergoing small bowel biopsy for suspected CD. Despite increased intestinal permeability, we see scant evidence of systemic exposure to gut microbes in these children. Gut permeability testing with L:R may predict which patients with abnormal celiac serology will have biopsy evidence for celiac disease and reduce the proportion of such patients undergoing endoscopy whose Marsh scores are ≤1. M should not be used as a monosaccharide for permeability testing in children.

Managing Symptom Profile of IBS-D Patients With Tritordeum-Based Foods: Results From a Pilot Study.

In the past few years, increasing attention has been given to the pathologic role of specific foods in IBS, like wheat and other cereals. Recent literature describes IBS patients who may experience gastrointestinal (GI) and extra-GI symptoms precipitated by the ingestion of cereals. Tritordeum is a cereal of Spanish origin derived from the hybridization of durum wheat and wild barley. It is different from classic wheat for its gluten protein composition, with fewer carbohydrates and fructans and a higher content of proteins, dietary fibers, and antioxidants. This pilot study aimed to investigate the effects of a 12-week diet with Tritordeum-based foods in substitution of other cereals on the profile of GI symptoms (evaluated by appropriate questionnaire) and the health of the GI barrier (assessed by sugar absorption test and different markers of integrity and functions) in 16 diarrhea-predominant IBS (IBS-D) patients. The diet with Tritordeum-based foods (bread, bakery products, and pasta) significantly reduced IBS-D patients' symptoms. This amelioration appears to occur through an overall improvement of the GI barrier, as demonstrated by the reduced intestinal permeability and the decreased levels of markers of intestinal mucosal integrity, mucosal inflammation, and fermentative dysbiosis.

No protective benefits of low dose acute L-glutamine supplementation on small intestinal permeability, epithelial injury and bacterial translocation biomarkers in response to subclinical exertional-heat stress: A randomized cross-over trial

ABSTRACT Exertional heat stress disrupts gastrointestinal permeability and, through subsequent bacterial translocation, can result in potentially fatal exertional heat stroke. Glutamine supplementation is a potential countermeasure although previously validated doses are not universally well tolerated. Ten males completed two 80-minute subclinical exertional heat stress tests (EHSTs) following either glutamine (0.3 g kg FFM−1) or placebo supplementation. Small intestinal permeability was assessed using the lactulose/rhamnose dual sugar absorption test and small intestinal epithelial injury using Intestinal Fatty-Acid Binding Protein (I-FABP). Bacterial translocation was assessed using the total 16S bacterial DNA and Bacteroides/total 16S DNA ratio. The glutamine bolus was well tolerated, with no participants reporting symptoms of gastrointestinal intolerance. Small intestinal permeability was not influenced by glutamine supplementation (p = 0.06) although a medium effect size favoring the placebo trial was observed (d = 0.73). Both small intestinal epithelial injury (p < 0.01) and Bacteroides/total 16S DNA (p = 0.04) increased following exertional heat stress, but were uninfluenced by glutamine supplementation. Low-dose acute oral glutamine supplementation does not protect gastrointestinal injury, permeability, or bacterial translocation in response to subclinical exertional heat stress.

Effects of water quality on growth performance and health of nursery pigs.

An experiment was conducted to determine the effects of providing drinking water of differing qualities on growth performance and health of nursery pigs. Weanling pigs (n = 450; 150 pigs/group; 10 pigs/pen) were assigned randomly to one of three experimental groups consisting of three water sources of varying qualities: 1) Water source A containing 1,410 ppm hardness (CaCO3 equivalent), 1,120 ppm sulfates, and 1,500 ppm total dissolved solids (TDS); 2) Water source B containing 909 ppm hardness (CaCO3 equivalent), 617 ppm sulfates, and 1,050 ppm TDS; and 3) Water source C containing 235 ppm hardness (CaCO3 equivalent), 2 ppm sulfates, and 348 ppm TDS. Pigs were provided ad libitum access to their respective water sources for the duration of the study which began at weaning (21 d of age) and ended 40 d later (61 d of age). Individual pig weights were recorded weekly along with feed intake on a pen basis. Occurrences of morbidity and mortality were recorded daily. Subjective fecal scores were assigned on a pen basis and blood samples were used to evaluate blood chemistry, cytokine concentrations, and phagocytic activity. A differential sugar absorption test was used to assess intestinal permeability. Fecal grab samples were used to establish diet digestibility, and drinking behavior was video-recorded to assess pigs’ acceptance of water sources provided. The statistical model considered fixed effects of water source, room, and their interaction with the random effect of pen. A repeated measures analysis was conducted to determine the effects of water quality over time. There were no differences (P > 0.440) among water sources in average daily gain (A, 0.46 kg/d; B, 0.46 kg/d; C, 0.47 kg/d) or average daily feed intake (A, 0.68 kg/d; B, 0.69 kg/d; C, 0.71 kg/d). Overall mortality of pigs was 0.44% and did not differ across the three water sources. There were no differences in apparent total tract digestibility of the diet, intestinal permeability, immune parameters, or blood chemistry attributable to quality of water consumed by pigs. Pigs did not show an aversion to the water sources provided, because total time pigs spent at the drinker did not differ (P > 0.750) among water sources on days 1 through 3 of the experiment. These data indicate that the water sources of differing quality studied did not affect growth performance or health of nursery pigs.