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Morphological Adaptation in the Jejunal Mucosa after Iso-Caloric High-Fat versus High-Carbohydrate Diets in Healthy Volunteers: Data from a Randomized Crossover Study.
Casselbrant, A, Wallenius, V, Elebring, E, Marschall, HU, Johansson, BR, Helander, HF, Fändriks, L
Nutrients. 2022;14(19)
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The small intestinal mucosa is a large organ which acts as an intestinal barrier. The jejunal mucosa is the largest part of the small intestinal mucosa, and its functions include digestion and absorption of food. Epithelium cells on the surface of the small intestine renew every few days. Therefore, this single-centre, randomised, unblinded, crossover study looked at how jejunal mucosal cells change after two weeks of an isocaloric high-fat diet (HFD) and high-carbohydrate diet (HCD) in fifteen healthy people. The study also measured ketogenesis rate-limiting enzyme 3-hydroxy-3-methylglutaryl-CoA synthase (HMGCS2) and mitochondria following the isocaloric HFD and HCD. Neither HFD nor HCD changes the mucosal surface enlargement factor. However, at the ultrastructural level, there was a significant surface enlargement in the bases of the villi after following HCD than HFD. In addition, HFD increased the number of mitochondrial cristae in the erythrocytes than HCD. The increased number of mitochondrial cristae in the erythrocytes was associated with the increased expression of HMGCS2. Healthcare professionals can use the results of this study to understand how short-term implementation of different diets affects jejunal mucosal morphology at the ultrastructural level. Further robust studies are required to evaluate the long-term effects of HFD and HCD in jejunal mucosa and how the morphological adaptations impact people with obesity.
Abstract
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.
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Protective effect of probiotics in patients with non-alcoholic fatty liver disease.
Cai, GS, Su, H, Zhang, J
Medicine. 2020;99(32):e21464
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Non-alcoholic fatty liver disease (NAFLD) is common in people with obesity and is characterised by high amounts of fat stored in the liver. Diet and exercise are the standard treatments, however recent studies have indicated that the gut microbiota may have an important role. This randomised control trial of 140 patients with NAFLD, aimed to assess the effect of probiotics when added to standard therapy for 3 months. The results showed that although gut microbiota, some aspects of liver function, blood lipids and blood sugars were all improved in individuals on standard therapy, there were additional improvements in those on standard therapy plus probiotics. It was concluded that although standard therapy alone is adequate to improve NAFLD, probiotics plus standard therapy was superior to standard therapy alone and effective in treatment of NAFLD. This study could be used by health professionals to justify the addition of probiotics to standard therapy to further improve NAFLD outcomes.
Abstract
To investigate the effects of probiotics on liver function, glucose and lipids metabolism, and hepatic fatty deposition in patients with non-alcoholic fatty liver disease (NAFLD).Totally 140 NAFLD cases diagnosed in our hospital from March 2017 to March 2019 were randomly divided into the observation group and control group, 70 cases in each. The control group received the diet and exercise therapy, while the observation group received oral probiotics based on the control group, and the intervention in 2 groups lasted for 3 months. The indexes of liver function, glucose and lipids metabolism, NAFLD activity score (NAS), and conditions of fecal flora in 2 groups were compared before and after the treatment.Before the treatment, there were no significant differences on alanine aminotransferase (ALT), aspartate aminotransferase (AST), glutamine transferase (GGT), total bilirubin (TBIL), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), insulin resistance index (HOMA-IR), NAFLD activity score (NAS), and conditions of fecal flora in 2 groups (P > .05). After the treatment, ALT, AST, GGT, TC, TG, HOMA-IR, NAS, and conditions of fecal flora in the observation group were better than those in the control group, and the observation group was better after treatment than before. All these above differences were statistically significant (P < .05).Probiotics can improve some liver functions, glucose and lipids metabolism, hepatic fatty deposition in patients with NAFLD, which will enhance the therapeutic effects of NAFLD.
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Modified Mediterranean-ketogenic diet modulates gut microbiome and short-chain fatty acids in association with Alzheimer's disease markers in subjects with mild cognitive impairment.
Nagpal, R, Neth, BJ, Wang, S, Craft, S, Yadav, H
EBioMedicine. 2019;47:529-542
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The exact causes of Alzheimer's disease (AD) are unknown, but there is evidence that AD is related to chronic inflammation, and it is thought that the gut bacteria (microbiome) and their metabolites can directly or indirectly affect brain functions. Diet can affect both the gut microbiome and brain health, and a ketogenic diet has been proposed to modulate processes associated with AD and is also known to affect gut microbial balance. The aim of this randomized, double-blind, crossover, pilot trial was to evaluate whether and how a modified Mediterranean-ketogenic diet (MMKD) alters the gut microbiome composition and whether this is associated with biomarkers for AD. 17 participants completed the study, 11 with mild cognitive impairment (MCI, an early stage of AD), and 6 counterparts with normal cognitive function (CN). Participants were randomly assigned to either a MMKD or an American Heart Association Diet (AHAD) for 6-weeks, followed by a 6-week washout, and then a 6-week intervention with the other diet. At baseline, participants with MCI had a microbiome composition different to that of the CN controls, with that of the MCI participants being considered less beneficial and potentially more pro-inflammatory. This difference was associated with biomarkers of AD. There was no difference in levels of microbial metabolites at baseline. Several types of bacteria were affected by the MMKD and AHAD, as were levels of faecal bacterial metabolites (short chain fatty acids). In particular, on the MMKD there was an increase in the metabolite butyrate which possesses neuroprotective actions and improves brain health. The authors conclude that the MMKD has a beneficial effect on the gut microbiome and associated AD biomarkers.
Abstract
BACKGROUND Alzheimer's disease (AD) prevalence is increasing, but its etiology remains elusive. Gut microbes can contribute to AD pathology and may help identifying novel markers and therapies against AD. Herein, we examine how the gut microbiome differs in older adults with mild cognitive impairment compared to cognitively normal counterparts, and whether and how a modified Mediterranean-ketogenic diet (MMKD) alters the gut microbiome signature in association with cerebrospinal fluid (CSF) AD biomarkers. METHODS A randomized, double-blind, cross-over, single-center pilot study of MMKD versus American Heart Association Diet (AHAD) intervention is performed on 17 subjects (age: 64.6 ± 6.4 yr), of which 11 have mild cognitive impairment, while 6 are cognitively normal. Subjects undergo MMKD and AHAD intervention for 6-weeks separated by 6-weeks washout periods. Gut microbiome, fecal short-chain fatty acids (SCFAs), and markers of AD in CSF including amyloid β (Aβ)-40 and Aß-42, total tau, and phosphorylated tau-181 (tau-p181) are measured at before and after diet interventions. FINDINGS At baseline, subjects with normal vs. impaired cognition show no notable difference in microbiome diversity but several unique microbial signatures are detected in subjects with mild cognitive impairment. Proteobacteria correlate positively with Aβ-42: Aβ-40 while fecal propionate and butyrate correlates negatively with Aβ-42 in subjects with mild cognitive impairment. Several bacteria are differently affected by the two diets with distinct patterns between cognitively normal and impaired subjects. Notably, the abundance of Enterobacteriaceae, Akkermansia, Slackia, Christensenellaceae and Erysipelotriaceae increases while that of Bifidobacterium and Lachnobacterium reduces on MMKD, while AHAD increases Mollicutes. MMKD slightly reduces fecal lactate and acetate while increasing propionate and butyrate. Conversely, AHAD increases acetate and propionate while reducing butyrate. INTERPRETATION The data suggest that specific gut microbial signatures may depict the mild cognitive impairment and that the MMKD can modulate the gut microbiome and metabolites in association with improved AD biomarkers in CSF.
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Effect of a Preparation of Four Probiotics on Symptoms of Patients with Irritable Bowel Syndrome: Association with Intestinal Bacterial Overgrowth.
Leventogiannis, K, Gkolfakis, P, Spithakis, G, Tsatali, A, Pistiki, A, Sioulas, A, Giamarellos-Bourboulis, EJ, Triantafyllou, K
Probiotics and antimicrobial proteins. 2019;11(2):627-634
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Irritable bowel syndrome (IBS) is the most common functional gut disorder with symptoms primarily of bloating and diarrhea. Recently these symptoms have been associated with small intestinal bacterial overgrowth (SIBO), which occurs when bacteria from the colon resides in the small intestine. The aim of this study was to determine the efficacy of probiotics in improvement of symptoms of IBS patients with SIBO. In this prospective trial, five patients with IBS and SIBO and 21 patients with IBS without SIBO were given probiotic capsules twice a day for 30 days. Participants completed an IBS severity questionnaire at three visits throughout the trial. At the end of the trial, a 71.3% decrease of the total IBS score was detected in patients with IBS and SIBO, compared with those without SIBO. This study found there are clinical benefits from probiotic supplementation in IBS patients with SIBO. Based on these findings, the authors conclude larger, randomised studies be undertaken based on this prospective design.
Abstract
The effect of probiotics on small intestinal bacterial overgrowth (SIBO) in irritable bowel syndrome (IBS) has never been studied so far. In this prospective trial, five patients with IBS and SIBO and 21 patients with IBS without SIBO were administered an oral capsule containing Saccharomyces boulardii, Bifidobacterium lactis, Lactobacillus acidophilus, and Lactobacillus plantarum (Lactolevure®) every 12 h for 30 days. SIBO was defined by quantitative culture of the third part of the duodenum; IBS was defined by the Rome III criteria. Severity of symptoms was graded by the IBS severity scoring system (SSS). The primary study endpoint was the efficacy of probiotics in improvement of symptoms of IBS in patients with SIBO. Thirty days after the end of treatment, a 71.3% decrease of the total IBS score was detected in patients with IBS and SIBO compared to 10.6% in those without SIBO (p 0.017). A similar decrease was achieved among patients with constipation-predominant IBS without SIBO. Post-treatment satisfaction from bowel function was greater in patients with SIBO. Similar satisfaction improvement was found among patients with diarrhea-predominant IBS irrespective from SIBO; pain intensity score decreased in patients with constipation-predominant IBS irrespective from SIBO. The benefit of probiotics was greater among patients with a pro-inflammatory cytokine pattern in the duodenal fluid. This is the first study that prospectively demonstrated superior clinical efficacy of probiotics in patients with IBS with SIBO. Analysis also showed considerable benefit from probiotic intake regarding certain symptoms of patients with diarrhea-predominant and constipation-predominant IBS.Trial registration: ClinicalTrials.gov identifier NCT02204891.
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Prolonged Collagen Peptide Supplementation and Resistance Exercise Training Affects Body Composition in Recreationally Active Men.
Kirmse, M, Oertzen-Hagemann, V, de Marées, M, Bloch, W, Platen, P
Nutrients. 2019;11(5)
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Currently little is known concerning collagen protein supplementation combined with a prolonged resistance exercising training (RET) programme. The aim of this study was to determine the effects of long-term collagen peptide supplementation and RET on body composition, strength and muscle fibre cross-sectional surface area (fCSA) in 57 recreationally active men. In this double-blind, placebo-controlled study, participants were randomly allocated to receive either collagen peptides or placebo for 12 weeks. Both groups trained three times a week. Strength testing, bioimedance analysis and muscle biopsies were taken at baseline and post-intervention. Most notably the collagen group experienced a significant increase in fat-free mass while body fat mass remained unchanged, compared to the placebo group. Both groups showed significant increases in strength tests and the fCSA increased significantly without differences. Based on these results, the authors conclude collagen protein supplementation have positive impact on body composition however suggest further study include connective tissue in addition to muscle tissue to better understand the mechanisms underlying these changes.
Abstract
We aimed to determine the effects of long-term collagen peptide (CP) supplementation and resistance exercise training (RET) on body composition, strength, and muscle fiber cross-sectional area (fCSA) in recreationally active men. Fifty-seven young men were randomly and double-blinded divided into a group receiving either collagen peptides (COL, 15 g/day) or a placebo (PLA). Strength testing, bioimpedance analysis, and muscle biopsies were used prior to and after an RET intervention. Food record protocols were performed during the RET intervention. The groups trained three times a week for 12 weeks. Baseline parameters showed no differences between groups, and the external training load and dietary food intake were also similar. COL showed a significant increase in fat-free mass (FFM) compared with the placebo group (p < 0.05). Body fat mass (BFM) was unchanged in COL, whereas a significant increase in BFM was observed in PLA. Both groups showed significant increases in all strength tests, with a trend for a slightly more pronounced effect in COL. The fCSA of type II muscle fibers increased significantly in both groups without differences between the two groups. We firstly demonstrated improved body composition in healthy, recreationally active men subsequent to prolonged CP supplementation in combination with RET. As the observed increase in FFM was not reflected in differences in fCSA hypertrophy between groups, we assume enhanced passive connective tissue adaptations in COL due to CP intake.
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Functional variants in the sucrase-isomaltase gene associate with increased risk of irritable bowel syndrome.
Henström, M, Diekmann, L, Bonfiglio, F, Hadizadeh, F, Kuech, EM, von Köckritz-Blickwede, M, Thingholm, LB, Zheng, T, Assadi, G, Dierks, C, et al
Gut. 2018;67(2):263-270
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Congenital sucrase-isomaltase deficiency (CSID) is a genetic disorder which results in a lower ability to digest certain sugars, resulting in diarrhoea, abdominal pain and bloating, which are also common symptoms of Irritable Bowel Syndrome (IBS). The objective of this study was to test sucrase-isomaltase (SI) gene variants for their potential relevance in IBS. The researchers looked at genetics in several populations with and without IBS. The researchers found that genetic mutations are associated with a 35% reduction in the activity of the SI enzymes. CSID mutations were almost twice as common in IBS patients than healthy controls. The genetic variant 15Phe was associated with diarrhoea, stool frequency and changes in the gut bacteria. The authors concluded that people with SI gene variants associated with reduced enzyme activity are more at risk of IBS. Genetic screening could help to identify individuals at increased risk of IBS, and may lead to more targeted treatment for some people with IBS.
Abstract
OBJECTIVE IBS is a common gut disorder of uncertain pathogenesis. Among other factors, genetics and certain foods are proposed to contribute. Congenital sucrase-isomaltase deficiency (CSID) is a rare genetic form of disaccharide malabsorption characterised by diarrhoea, abdominal pain and bloating, which are features common to IBS. We tested sucrase-isomaltase (SI) gene variants for their potential relevance in IBS. DESIGN We sequenced SI exons in seven familial cases, and screened four CSID mutations (p.Val557Gly, p.Gly1073Asp, p.Arg1124Ter and p.Phe1745Cys) and a common SI coding polymorphism (p.Val15Phe) in a multicentre cohort of 1887 cases and controls. We studied the effect of the 15Val to 15Phe substitution on SI function in vitro. We analysed p.Val15Phe genotype in relation to IBS status, stool frequency and faecal microbiota composition in 250 individuals from the general population. RESULTS CSID mutations were more common in patients than asymptomatic controls (p=0.074; OR=1.84) and Exome Aggregation Consortium reference sequenced individuals (p=0.020; OR=1.57). 15Phe was detected in 6/7 sequenced familial cases, and increased IBS risk in case-control and population-based cohorts, with best evidence for diarrhoea phenotypes (combined p=0.00012; OR=1.36). In the population-based sample, 15Phe allele dosage correlated with stool frequency (p=0.026) and Parabacteroides faecal microbiota abundance (p=0.0024). The SI protein with 15Phe exhibited 35% reduced enzymatic activity in vitro compared with 15Val (p<0.05). CONCLUSIONS SI gene variants coding for disaccharidases with defective or reduced enzymatic activity predispose to IBS. This may help the identification of individuals at risk, and contribute to personalising treatment options in a subset of patients.
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Disruption of maternal gut microbiota during gestation alters offspring microbiota and immunity.
Nyangahu, DD, Lennard, KS, Brown, BP, Darby, MG, Wendoh, JM, Havyarimana, E, Smith, P, Butcher, J, Stintzi, A, Mulder, N, et al
Microbiome. 2018;6(1):124
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The gut microbiota is key for immune development, especially during a critical window in infancy, and it has been shown that maternal diet before, during and after pregnancy influences infant metabolism and gut microbiota. The aim of this study was to assess the effects of maternal antibiotics administration during gestation and nursing on offspring gut microbiota and immunity. Pregnant mice, dams, received oral vancomycin in drinking water 5 days prior to give birth (gestation group), 14 days after delivery (nursing group) or 5 days prior to delivery and throughout nursing (gestation plus nursing group), while control mice received no vancomycin. Adaptive immunity and gut microbiota in dams and pups were analysed at various times after delivery. This study showed that antibiotic alteration of maternal gut microbiota during both pregnancy and nursing results in changes in the adaptive immunity in offspring. The authors conclude these findings are important as they provide insight into the mechanism by which maternal exposures during pregnancy may impact infant health, therefore identifying potential targets for intervention.
Abstract
BACKGROUND Early life microbiota is an important determinant of immune and metabolic development and may have lasting consequences. The maternal gut microbiota during pregnancy or breastfeeding is important for defining infant gut microbiota. We hypothesized that maternal gut microbiota during pregnancy and breastfeeding is a critical determinant of infant immunity. To test this, pregnant BALB/c dams were fed vancomycin for 5 days prior to delivery (gestation; Mg), 14 days postpartum during nursing (Mn), or during gestation and nursing (Mgn), or no vancomycin (Mc). We analyzed adaptive immunity and gut microbiota in dams and pups at various times after delivery. RESULTS In addition to direct alterations to maternal gut microbial composition, pup gut microbiota displayed lower α-diversity and distinct community clusters according to timing of maternal vancomycin. Vancomycin was undetectable in maternal and offspring sera, therefore the observed changes in the microbiota of stomach contents (as a proxy for breastmilk) and pup gut signify an indirect mechanism through which maternal intestinal microbiota influences extra-intestinal and neonatal commensal colonization. These effects on microbiota influenced both maternal and offspring immunity. Maternal immunity was altered, as demonstrated by significantly higher levels of both total IgG and IgM in Mgn and Mn breastmilk when compared to Mc. In pups, lymphocyte numbers in the spleens of Pg and Pn were significantly increased compared to Pc. This increase in cellularity was in part attributable to elevated numbers of both CD4+ T cells and B cells, most notable Follicular B cells. CONCLUSION Our results indicate that perturbations to maternal gut microbiota dictate neonatal adaptive immunity.
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Inflammatory bowel diseases: a burden in pediatrics: Case series and a review of the literature.
Mărginean, CO, Meliţ, LE, Mocanu, S, Mărginean, MO
Medicine. 2017;96(11):e6329
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Inflammatory bowel disease (IBD) is a disorder of the digestive tract and is of two types –Ulcerative colitis and Crohn’s disease. IBD can occur at any age but it seems, it's on increase in children especially in developed countries. The etiology of IBD is not fully understood, though the prognosis depends on the number of relapses. This study is a review based on four cases of IBD presenting in children under the age of 16. The authors found that emotional disorders and stress are often the common factors encountered in IBD patients. Also, a diet high in animal fat and low in fruit and vegetable seems to be associated with increased risk of IBD. The authors concluded that intervention of defined formula diet and supplementation of vitamin D showed positive outcomes in IBD sufferers. However, alongside medical approach for the treatment of IBD, educational intervention as well as addressing the emotional disorders may be helpful in the management of IBD.
Abstract
INTRODUCTION Inflammatory bowel disease is a chronic condition of the gastrointestinal tract, comprising mainly Crohn disease (CD) and ulcerative colitis (UC). Both of them are frequently encountered in children, being multifactorial conditions, with an unclear etiology. PATIENTS CONCERNS We present 4 cases of inflammatory bowel disease (IBD) in children in order to underline the variable evolution depending on the patient's particularities. DIAGNOSIS, INTERVENTIONS AND OUTCOMES The first case, a 13-year-old male patient, with a history of Henoch-Schonlein purpura, was admitted for rectal bleeding and weight loss, with normal laboratory parameters. The colonoscopy and the histopathological examination established the diagnosis of UC. The evolution was initially favorable under corticosteroids and sulfasalazine, but with 3 relapses in 2 years. The second case, a 16-year-old male patient, with a history of lactose intolerance and constipation, was admitted for bloody, diarrheic stools, the laboratory tests pointing out only leukocytosis with neutrophilia. The colonoscopy and histopathological examination established the diagnosis of UC. The patient's evolution was slowly favorable. The third case, a 9-year old male patient, with emotional disorders and babbling, admitted for semiconsistent, bloody stools, with increased inflammatory tests, whose colonoscopy pointed out diffuse edema and hemorrhages, the histopathological examination establishing the diagnosis of CD. The evolution was initially favorable, but with 5 relapses in 3 years. The last case, a 12-year-old male patient, was admitted with diarrheic, bloody stools, refractory to antibiotics, and weight loss, with increased inflammatory tests. The colonoscopy pointed out ulcerations, hemorrhages, and disseminated puss deposits. The histopathological examination established the diagnosis of CD. The patient's evolution was favorable, with only 1 relapse in 3 years. CONCLUSIONS The adequate management, especially the self-management can influence the prognosis of patients with IBD, even though it is unpredictable and burdened by the risk of malignant transformation.
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Randomised clinical study: Aspergillus niger-derived enzyme digests gluten in the stomach of healthy volunteers.
Salden, BN, Monserrat, V, Troost, FJ, Bruins, MJ, Edens, L, Bartholomé, R, Haenen, GR, Winkens, B, Koning, F, Masclee, AA
Alimentary pharmacology & therapeutics. 2015;42(3):273-85
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Gluten is high in proline, an amino acid that is not naturally broken down in the human gastrointestinal tract. In patients with coeliac disease, proline-rich gluten reaches the small intestine and triggers an abnormal immune response, causing inflammation and microvilli damage. The aim of this randomised study was to test the efficacy of Aspergillus niger prolyl endoprotease (AN-PEP) on gluten degradation. AN-PEP belongs to a family of enzymes that has been previously known to break down proline in vitro. The study included 12 healthy volunteers aged 18-45 who were administered a low or high calorie meal containing 4.0g of gluten protein, with AN-PEP or placebo into the stomach. The findings of this study showed that AN-PEP significantly enhanced gluten digestion in the stomach before entering the duodenum of healthy volunteers. Based on this study, the authors conclude that AN-PEP is a promising option for degrading inadvertent dietary gluten consumption, and should be evaluated in target populations.
Abstract
BACKGROUND Aspergillus niger prolyl endoprotease (AN-PEP) efficiently degrades gluten molecules into non-immunogenic peptides in vitro. AIM: To assess the efficacy of AN-PEP on gluten degradation in a low and high calorie meal in healthy subjects. METHODS In this randomised, double-blind, placebo-controlled, cross-over study 12 healthy volunteers attended to four test days. A liquid low or high calorie meal (4 g gluten) with AN-PEP or placebo was administered into the stomach. Via a triple-lumen catheter gastric and duodenal aspirates were sampled, and polyethylene glycol (PEG)-3350 was continuously infused. Acetaminophen in the meals tracked gastric emptying time. Gastric and duodenal samples were used to calculate 240-min area under the curve (AUC0-240 min ) of ?-gliadin concentrations. Absolute ?-gliadin AUC0-240 min was calculated using duodenal PEG-3350 concentrations. RESULTS AN-PEP lowered α-gliadin concentration AUC0-240 min, compared to placebo, from low and high calorie meals in stomach (low: 35 vs. 389 μg × min/mL; high: 53 vs. 386 μg × min/mL; P < 0.001) and duodenum (low: 7 vs. 168 μg × min/mL; high: 4 vs. 32 μg × min/mL; P < 0.001) and absolute α-gliadin AUC0-240 min in the duodenum from low (2813 vs. 31 952 μg × min; P < 0.001) and high (2553 vs. 13 095 μg × min; P = 0.013) calorie meals. In the placebo group, the high compared to low calorie meal slowed gastric emptying and lowered the duodenal α-gliadin concentration AUC0-240 min (32 vs. 168 μg × min/mL; P = 0.001). CONCLUSIONS AN-PEP significantly enhanced gluten digestion in the stomach of healthy volunteers. Increasing caloric density prolonged gastric residence time of the meal. Since AN-PEP already degraded most gluten from low calorie meals, no incremental effect was observed by increasing meal caloric density. ClinicalTrials.gov, Number: NCT01335503; www.trialregister.nl, Number: NTR2780.
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Effect of gliadin on permeability of intestinal biopsy explants from celiac disease patients and patients with non-celiac gluten sensitivity.
Hollon, J, Puppa, EL, Greenwald, B, Goldberg, E, Guerrerio, A, Fasano, A
Nutrients. 2015;7(3):1565-76
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Celiac disease (CD) and non-celiac gluten sensitivity (GS) are conditions caused by a reaction to gluten in the small intestines. When gluten is ingested, patients with CD produce an immune-mediated response in the intestinal mucosa whereas GS react symptomatically but do not produce an immune response. Due to this difference, it is thought that there may be a common defect in the intestinal barrier function in these two conditions. The aim of this study was to evaluate the response to gliadin exposure, both in terms of intestinal barrier function and immune cell secretion. Gliadin is a peptide in gluten that is responsible for the disassembly of intestinal tight junctions and therefore increased intestinal permeability. The study included intestinal explants from 23 patients. The findings of this study showed that gliadin exposure leads to a significant increase in intestinal permeability in all individuals. A deficiency in anti-inflammatory immune cells was also measured in patients with CD or GS, which is suggested to contribute to increased intestinal permeability.
Abstract
BACKGROUND Intestinal exposure to gliadin leads to zonulin upregulation and consequent disassembly of intercellular tight junctions and increased intestinal permeability. We aimed to study response to gliadin exposure, in terms of barrier function and cytokine secretion, using intestinal biopsies obtained from four groups: celiac patients with active disease (ACD), celiac patients in remission (RCD), non-celiac patients with gluten sensitivity (GS) and non-celiac controls (NC). METHODS Ex-vivo human duodenal biopsies were mounted in microsnapwells and luminally incubated with either gliadin or media alone. Changes in transepithelial electrical resistance were monitored over 120 min. Media was subsequently collected and cytokines quantified. RESULTS Intestinal explants from all groups (ACD (n = 6), RCD (n = 6), GS (n = 6), and NC (n = 5)) demonstrated a greater increase in permeability when exposed to gliadin vs. media alone. The increase in permeability in the ACD group was greater than in the RCD and NC groups. There was a greater increase in permeability in the GS group compared to the RCD group. There was no difference in permeability between the ACD and GS groups, between the RCD and NC groups, or between the NC and GS groups. IL-10 was significantly greater in the media of the NC group compared to the RCD and GS groups. CONCLUSIONS Increased intestinal permeability after gliadin exposure occurs in all individuals. Following gliadin exposure, both patients with gluten sensitivity and those with active celiac disease demonstrate a greater increase in intestinal permeability than celiacs in disease remission. A higher concentration of IL-10 was measured in the media exposed to control explants compared to celiac disease in remission or gluten sensitivity.