Minimally Invasive Image-Guided Gut Transport Function Measurement Probe

Introduction: Diseases such as celiac disease, environmental enteric dysfunction, infectious gastroenteritis, type II diabetes and inflammatory bowel disease are associated with increased gut permeability. Dual sugar absorption tests, such as the lactulose to rhamnose ratio (L:R) test, are the current standard for measuring gut permeability. Although easy to administer in adults, the L:R test has a number of drawbacks. These include an inability to assess for spatial heterogeneity in gut permeability that may distinguish different disease severity or pathology, additional sample collection for immunoassays, and challenges in carrying out the test in certain populations such as infants and small children. Here, we demonstrate a minimally invasive probe for real-time localized gut permeability evaluation through gut potential difference (GPD) measurement.Materials and Methods: The probe has an outer diameter of 1.2 mm diameter and can be deployed in the gut of unsedated subjects via a transnasal introduction tube (TNIT) that is akin to an intestinal feeding tube. The GPD probe consists of an Ag/AgCl electrode, an optical probe and a perfusion channel all housed within a transparent sheath. Lactated Ringer’s (LR) solution is pumped through the perfusion channel to provide ionic contact between the electrodes and the gut lining. The optical probe captures non-scanning (M-mode) OCT images to confirm electrode contact with the gut lining. A separate skin patch probe is placed over an abraded skin area to provide reference for the GPD measurements. Swine studies were conducted to validate the GPD probe. GPD in the duodenum was modulated by perfusing 45 ml of 45 mM glucose.Results: GPD values of −13.1 ± 2.8 mV were measured in the duodenum across four swine studies. The change in GPD in the duodenum with the addition of glucose was −10.5 ± 2.4 mV (p < 0.001). M-mode OCT images provided electrode-tissue contact information, which was vital in ascertaining the probe’s proximity to the gut mucosa.Conclusion: We developed and demonstrated a minimally invasive method for investigating gastrointestinal permeability consisting of an image guided GPD probe that can be used in unsedated subjects.

Improvement of roasted germinated brown rice flour processing using ergothioneine to limit oxidation during processing and preservation

Roasting temperature and time are important parameters in the process of roasted germinated brown rice flour (RGBRF), which cause the loss of bioactive ingredients and sensory value of the product. During roasting and storage, fat oxidation is also one of the problems that reduce the quality of RGBRF. In order to complete the RGBRF process, experiments using different temperature and time as 160oC, 200oC, 240oC for 10 to 30 mins were done to find the best roasting conditions. To limit the oxidation of fat during the processing and preserving RGBRF, ergothioneine (ERG) extract from enoki mushroom were supplemented at 3%, 5%, 7% and 10% (w/w) before roasted, the product was then ground and put into two types of packaging (PA and aluminum), vacuum seamed and stored at room temperature for 8 weeks were carried out. The results showed that germinated brown rice (GBR) which supplemented 3% of the extract before roasted at 200oC for 30 mins showed the best quality in term of sensory value, γ-aminobutyric acid (GABA) content and helped to limit fat oxidation as well as maintained stable quality after 8 weeks of storage in PA and aluminum packaging. In addition, the results from in vitro of starch resistance and in vivo of sugar absorption capacity in rats showed that RGBRF did not significantly change the GI index as well as the ability to absorb sugar compared to unroasted product. The results indicated that RGBRF should be used as a nutritious food with the ability to supplement bioactive compounds to the people at risk of lifestyle diseases.

Artificial Sweeteners and Metabolic Syndrome: Paradox of Physiological Behavior or Neuroendocrine Mechanisms

Artificial sweeteners owing to their non-caloric nature were proposed as a healthful means with the prospective benefits. Epidemiological data indicate direct relationship between artificial sweetener intake and increase in body weight, glycemic status, and adiposity. Despite strong association, evidence is still lacking in establishing the causal relationship between artificial sweeteners and various risk factors for the development of metabolic syndrome. In vitro studies have disclosed that artificial sweeteners similar to glucose/fructose bind to sweet-taste receptors on the tongue and intestinal mucosa stimulating enhanced sugar absorption, through glucagon like peptide-1 (GLP-1) secretion. Human studies failed to recapitulate these effects, advocating that artificial sweeteners rather serve to promote food consumption rather than improving satiety. Therefore, enhanced food consumption, disallowance of caloric adjustments could in some measure explain body weight gain with the use of artificial sweeteners. However, the physiological behavior and neuroendocrine mechanisms by which the non-caloric sweeteners may stimulate appetite needs further scrutiny.

Starvation and Its Effects on the Gut

ABSTRACT There is growing awareness that intestinal dysfunction determines the clinical outcomes of situations as diverse as undernourished children in urban tropical slums and undernourished surgical patients in intensive care units. As experimental starvation in humans has only rarely been studied, and largely not using current biomedical research tools, we must draw inference from disparate clinical and experimental observations as to the derangements present in the starved gut. There is good evidence of intestinal atrophy and achlorhydria in starvation and severe undernutrition. Historical reports from concentration camps and conflict settings consistently reported a noncontagious phenomenon called “hunger diarrhea,” but in settings where starved individuals are isolated from others (prisoners on hunger strike, anorexia nervosa) diarrhea is not a feature. Changes in intestinal permeability and absorption have been infrequently studied in experimental starvation; available data suggest that short-term starvation reduces sugar absorption but not permeability. Severe acute malnutrition in children is associated with severe changes in the intestinal mucosa. Experimental animal models may help explain some observations in humans. Starved rats develop a hypersecretory state and intestinal barrier defects. Starved pigs demonstrate prolongation of rotavirus diarrhea and reproduce some of the absorptive and barrier defects observed in malnourished children. However, there remains much to be learned about the effects of starvation on the gut. Given the high prevalence of undernutrition in hospitals and disadvantaged communities, the lack of attention to the interaction between undernutrition and gastrointestinal damage is surprising and needs to be corrected. Current sophisticated cellular and molecular techniques now provide the opportunity to create fresh understanding of gastrointestinal changes in pure undernutrition, using volunteer studies and samples from anorexia nervosa.

Post-Delivery Milking Delay Influence on the Effect of Oral Supplementation with Bovine Colostrum as Measured with Intestinal Permeability Test

Background and objective: The health supplement bovine colostrum reportedly improves immunity and regulates intestinal homeostasis. Reliable assessment methods are needed to ensure the satisfactory biological activity of all marketed colostrum products. Of the well-established effects of colostrum use, the restoration of appropriate intestinal permeability assessed with the lactulose/mannitol (L/M) differential sugar absorption test upon supplementation with colostrum has been consistently observed. Milking time after delivery is one of the factors that influences the composition of bovine colostrum, which causes a rapid decrease in bioactive components. Materials and methods: We use the L/M test to evaluate the intestinal permeability reduction upon supplementation with colostrum (2 × 500 mg) harvested at various times after delivery (2, 24, and 72 h) or a placebo (whey). In our randomized, double-blind placebo-controlled (DBPC) trial, 31 healthy athletes were divided into four groups and assessed at baseline and after the intervention. Results: The trial revealed that only colostrum collected after 2 h and 24 h caused a significant reduction of intestinal permeability. The comparison of post-intervention vs. baseline Δ values produced statistically significant results for 2 h colostrum versus the placebo and 72 h colostrum groups. Conclusions: We conclude that the change of bovine colostrum composition over the first three days of lactation is accompanied by a decrease in its biological activity as measured with the L/M test. This test may offer a biological quality measure for colostrum.

Intestinal Permeability in Children with Celiac Disease after the Administration of Oligofructose-Enriched Inulin into a Gluten-Free Diet—Results of a Randomized, Placebo-Controlled, Pilot Trial

Abnormalities in the intestinal barrier are a possible cause of celiac disease (CD) development. In animal studies, the positive effect of prebiotics on the improvement of gut barrier parameters has been observed, but the results of human studies to date remain inconsistent. Therefore, this study aimed to evaluate the effect of twelve-week supplementation of a gluten-free diet (GFD) with prebiotic oligofructose-enriched inulin (10 g per day) on the intestinal permeability in children with CD treated with a GFD. A pilot, randomized, placebo-controlled nutritional intervention was conducted in 34 children with CD, being on a strict GFD. Sugar absorption test (SAT) and the concentrations of intestinal permeability markers, such as zonulin, intestinal fatty acid-binding protein, claudin-3, calprotectin, and glucagon-like peptide-2, were measured. We found that the supplementation with prebiotic did not have a substantial effect on barrier integrity. Prebiotic intake increased excretion of mannitol, which may suggest an increase in the epithelial surface. Most children in our study seem to have normal values for intestinal permeability tests before the intervention. For individuals with elevated values, improvement in calprotectin and SAT was observed after the prebiotic intake. This preliminary study suggests that prebiotics may have an impact on the intestinal barrier, but it requires confirmation in studies with more subjects with ongoing leaky gut.

Lactobacillus salivarius AP-32 and Lactobacillus reuteri GL-104 decrease glycemic levels and attenuate diabetes-mediated liver and kidney injury in db/db mice

ObjectivesPatients with type 2 diabetes mellitus (T2DM) exhibit strong insulin resistance or abnormal insulin production. Probiotics, which are beneficial live micro-organisms residing naturally in the intestinal tract, play indispensable roles in the regulation of host metabolism. However, the detailed mechanisms remain unclear. Here, we evaluate the mechanisms by which probiotic strains mediate glycemic regulation in the host. The findings should enable the development of a safe and natural treatment for patients with T2DM.Research designs and methodsSugar consumption by more than 20 strains of Lactobacillus species was first evaluated. The probiotic strains that exhibited high efficiency of sugar consumption were further coincubated with Caco-2 cells to evaluate the regulation of sugar absorption in gut epithelial cells. Finally, potential probiotic strains were selected and introduced into a T2DM animal model to study their therapeutic efficacy.ResultsAmong the tested strains, Lactobacillus salivarius AP-32 and L. reuteri GL-104 had higher monosaccharide consumption rates and regulated the expression of monosaccharide transporters. Glucose transporter type-5 and Na+-coupled glucose transporter mRNAs were downregulated in Caco-2 cells after AP-32 and GL-104 treatment, resulting in the modulation of intestinal hexose uptake. Animal studies revealed that diabetic mice treated with AP-32, GL-104, or both showed significantly decreased fasting blood glucose levels, improved glucose tolerance and blood lipid profiles, and attenuated diabetes-mediated liver and kidney injury.ConclusionOur data elucidate a novel role for probiotics in glycemic regulation in the host. L. salivarius AP-32 and L. reuteri GL-104 directly reduce monosaccharide transporter expression in gut cells and have potential as therapeutic probiotics for patients with T2DM.

Consuming a Diet of U.S. Military Food Rations Alters Fecal Microbiota Composition but Does Not Increase Intestinal Permeability (FS07-06-19)

Objectives Recent studies have reported altered fecal microbiota composition together with increased intestinal permeability (IP) and inflammation in individuals consuming military food rations in austere environments, but could not separate effects of the highly processed, commercially sterile ration-based diets from environmental factors. This study aimed to determine how the U.S. Meal, Ready-to-Eat (MRE) food ration affects fecal microbiota composition and IP. Methods In this parallel-arm trial, 60 adults (95% male, 18–61 yr) were randomly assigned to consume their usual diet for 31d (CON), or a strictly controlled MRE-only diet for 21d then their usual diet for 10d (MRE). Fecal samples were collected at baseline (BL, days -8–0), and during (INT, days 1–21) and after (POST, days 22–31) the intervention period to measure microbiota composition by 16S rDNA sequencing. On days 0, 10, 21 and 31 IP was measured by dual-sugar absorption test, and circulating markers of bacterial translocation from the gut lumen (LPS-binding protein (LBP)) and inflammation (hsCRP) were measured. Results During INT, carbohydrate (CON vs MRE: 44% vs 50% energy) and fiber (19 vs 26 g/d) intakes were lower in CON relative to MRE, whereas protein intake was higher (18% vs. 13% energy) (P ≤ 0.01). Body weight increased over time in CON, but transiently decreased during INT in MRE (P = 0.001). Changes in fecal microbiota composition differed over time between groups (P ≤ 0.01), with random forest models discriminating the fecal microbiota of MRE and CON samples during INT with 88% accuracy. The most discriminant genera included multiple bacteria used in food production (Lactobacillus, Lactococcus, Streptococcus, Leuconostoc) which were less abundant in MRE, and the inflammation-associated genus Sutterella which transiently increased in MRE during INT. IP and hsCRP were both lower (25% and 16%, respectively) in MRE relative to CON on day 21 (P < 0.05), but did not differ before or after. LBP did not differ between groups at any time. Conclusions Findings suggest that a highly processed, commercially sterile MRE-only diet reduces the proportions of diet-derived bacteria in the gut microbiota and does not increase IP or inflammation. Funding Sources US Army Medical Research and Materiel Command. Authors’ views do not reflect official DoD or Army policy.

Intestinal Permeability Measured by Urinary Sucrose Excretion Correlates with Serum Zonulin and Faecal Calprotectin Concentrations in UC Patients in Remission

Background and Aims. Ulcerative colitis (UC) is associated with an increased intestinal permeability, possibly through a dysbiosis of intestinal bacteria. We investigated which markers are most relevant to assess intestinal permeability in UC patients and whether probiotics had an effect on these markers. Methods. In this twelve-week placebo-controlled randomized double-blind study, twenty-five subjects with UC in remission received either placebo or a multispecies probiotics. Samples of blood, urine, and faeces were taken at baseline, week 6, and week 12 to assess intestinal permeability and inflammation. Diaries and Bristol stool scale were kept to record stool frequency and consistency. Quality of life was scored from 32–224 with the inflammatory bowel disease questionnaire (IBD-Q). Results. This group of UC patients, in clinical remission, did not show increased intestinal permeability at baseline of this study. During the study, no significant group or time effects were found for intestinal permeability measured by the 5-sugar absorption test, serum zonulin, and faecal zonulin. Likewise, the inflammatory markers C-reactive protein (CRP), calprotectin, and the cytokines IFNγ, TNFα, IL-6, and IL-10 were not significantly affected. Stool frequency and consistency were not significantly affected either. The IBD-Q score, 194 for the probiotics group and 195 for the placebo group, remained unaffected. Correlations were tested between all outcomes; urinary sucrose excretion was significantly correlated with serum zonulin (r = 0.62) and faecal calprotectin (r = 0.55). Faecal zonulin was not significantly correlated with any of the other markers. Conclusion. Serum zonulin may be a more relevant biomarker of intestinal permeability than faecal zonulin, due to its correlation with other biomarkers of intestinal permeability. UC patients in remission did not show an effect of the probiotic treatment or a change in gut permeability. This should not discourage further studies because effects might be present during active disease or shortly after a flare up.