Duodenal alpha-Synuclein Pathology and Enteric Gliosis in Advanced Parkinson's Disease.

BACKGROUND: The role of the gut-brain axis has been recently highlighted as a major contributor to Parkinson's disease (PD) physiopathology, with numerous studies investigating bidirectional transmission of pathological protein aggregates, such as α-synuclein (αSyn). However, the extent and the characteristics of pathology in the enteric nervous system have not been fully investigated. OBJECTIVE: We characterized αSyn alterations and glial responses in duodenum biopsies of patients with PD by employing topography-specific sampling and conformation-specific αSyn antibodies. METHODS: We examined 18 patients with advanced PD who underwent Duodopa percutaneous endoscopic gastrostomy and jejunal tube procedure, 4 untreated patients with early PD (disease duration <5 years), and 18 age- and -sex-matched healthy control subjects undergoing routine diagnostic endoscopy. A mean of four duodenal wall biopsies were sampled from each patient. Immunohistochemistry was performed for anti-aggregated αSyn (5G4) and glial fibrillary acidic protein antibodies. Morphometrical semiquantitative analysis was performed to characterize αSyn-5G4+ and glial fibrillary acidic protein-positive density and size. RESULTS: Immunoreactivity for aggregated α-Syn was identified in all patients with PD (early and advanced) compared with controls. αSyn-5G4+ colocalized with neuronal marker ß-III-tubulin. Evaluation of enteric glial cells demonstrated an increased size and density when compared with controls, suggesting reactive gliosis. CONCLUSIONS: We found evidence of synuclein pathology and gliosis in the duodenum of patients with PD, including early de novo cases. Future studies are required to evaluate how early in the disease process duodenal pathology occurs and its possible contribution to levodopa effect in chronic patients. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Durable metabolic improvements 2 years after duodenal mucosal resurfacing (DMR) in patients with type 2 diabetes (REVITA-1 Study).

AIMS: Duodenal mucosal resurfacing (DMR) is an endoscopic procedure developed to improve metabolic parameters and restore insulin sensitivity in patients with diabetes. Here we report long-term DMR safety and efficacy from the REVITA-1 study. MATERIALS AND METHODS: REVITA-1 was a prospective, single-arm, open-label, multicenter study of DMR feasibility, safety, and efficacy in patients with type 2 diabetes (hemoglobin A1c [HbA1c] of 7.5-10.0% (58-86 mmol/mol)) on oral medication. Safety and glycemic (HbA1c), hepatic (alanine aminotransferase [ALT]), and cardiovascular (HDL, triglyceride [TG]/HDL ratio) efficacy parameters were assessed (P values presented for LS mean change). RESULTS: Mean ± SD HbA1c levels reduced from 8.5 ± 0.7% (69.1 ± 7.1 mmol/mol) at baseline (N = 34) to 7.5 ± 0.8% (58.9 ± 8.8 mmol/mol) at 6 months (P < 0.001); and this reduction was sustained through 24 months post-DMR (7.5 ± 1.1% [59.0 ± 12.3 mmol/mol], P < 0.001) while in greater than 50% of patients, glucose-lowering therapy was reduced or unchanged. ALT decreased from 38.1 ± 21.1 U/L at baseline to 32.5 ± 22.1 U/L at 24 months (P = 0.048). HDL and TG/HDL improved during 24-months of follow-up. No device- or procedure-related serious adverse events, unanticipated device effects, or hypoglycemic events were noted between 12 and 24 months post-DMR. CONCLUSIONS: DMR is associated with durable improvements in insulin sensitivity and multiple downstream metabolic parameters through 24 months post-treatment in type 2 diabetes. Clinical trial reg. no. NCT02413567, clinicaltrials.gov.

Hepcidin and Iron Deficiency in Women One Year after Sleeve Gastrectomy: A Prospective Cohort Study.

Iron deficiency with or without anemia, needing continuous iron supplementation, is very common in obese patients, particularly those requiring bariatric surgery. The aim of this study was to address the impact of weight loss on the rescue of iron balance in patients who underwent sleeve gastrectomy (SG), a procedure that preserves the duodenum, the main site of iron absorption. The cohort included 88 obese women; sampling of blood and duodenal biopsies of 35 patients were performed before and one year after SG. An analysis of the 35 patients consisted in evaluating iron homeostasis including hepcidin, markers of erythroid iron deficiency (soluble transferrin receptor (sTfR) and erythrocyte protoporphyrin (PPIX)), expression of duodenal iron transporters (DMT1 and ferroportin) and inflammatory markers. After surgery, sTfR and PPIX were decreased. Serum hepcidin levels were increased despite the significant reduction in inflammation. DMT1 abundance was negatively correlated with higher level of serum hepcidin. Ferroportin abundance was not modified. This study shed a new light in effective iron recovery pathways after SG involving suppression of inflammation, improvement of iron absorption, iron supply and efficiency of erythropoiesis, and finally beneficial control of iron homeostasis by hepcidin. Thus, recommendations for iron supplementation of patients after SG should take into account these new parameters of iron status assessment.

Gliadin, through the Activation of Innate Immunity, Triggers lncRNA NEAT1 Expression in Celiac Disease Duodenal Mucosa.

Celiac disease (CD) is an autoimmune enteropathy arising in genetically predisposed subjects exposed to gluten, which activates both innate and adaptive immunity. Although the pathogenesis is common to all patients, the clinical spectrum is quite variable, and differences could be explained by gene expression variations. Among the factors able to affect gene expression, there are lncRNAs. We evaluated the expression profile of 87 lncRNAs in CD vs. healthy control (HC) intestinal biopsies by RT-qPCR array. Nuclear enriched abundant transcript 1 (NEAT1) and taurine upregulated gene 1 (TUG1) were detected as downregulated in CD patients at diagnosis, but their expression increased in biopsies of patients on a gluten-free diet (GFD) exposed to gluten. The increase in NEAT1 expression after gluten exposure was mediated by IL-15 and STAT3 activation and binding to the NEAT1 promoter, as demonstrated by gel shift assay. NEAT1 is localized in the nucleus and can regulate gene expression by sequestering transcription factors, and it has been implicated in immune regulation and control of cell proliferation. The demonstration of its regulation by gluten thus also supports the role of lncRNAs in CD and prompts further research on these RNAs as gene expression regulators.

Impaired Duodenal Palmitoylethanolamide Release Underlies Acid-Induced Mast Cell Activation in Functional Dyspepsia.

BACKGROUND & AIMS: Acid hypersensitivity is claimed to be a symptomatic trigger in functional dyspepsia (FD); however, the neuroimmune pathway(s) and the mediators involved in this process have not been investigated systematically. Palmitoylethanolamide (PEA) is an endogenous compound, able to modulate nociception and inflammation, but its role in FD has not been assessed. METHODS: Duodenal biopsy specimens from FD and control subjects, and peroxisome proliferator-activated receptor-α (PPARα) null mice were cultured at a pH of 3.0 and 7.4. Mast cell (MC) number, the release of their mediators, and the expression of transient receptor potential vanilloid receptor (TRPV)1 and TRPV4, were evaluated. All measurements also were performed in the presence of a selective blocker of neuronal action potential (tetradotoxin). FD and control biopsy specimens in acidified medium also were incubated in the presence of different PEA concentrations, alone or combined with a selective PPARα or PPAR-γ antagonist. RESULTS: An acid-induced increase in MC density and the release of their mediators were observed in both dyspeptic patients and controls; however, this response was amplified significantly in FD. This effect was mediated by submucosal nerve fibers and up-regulation of TRPV1 and TRPV4 receptors because pretreatment with tetradotoxin significantly reduced MC infiltration. The acid-induced endogenous release of PEA was impaired in FD and its exogenous administration counteracts MC activation and TRPV up-regulation. CONCLUSIONS: Duodenal acid exposure initiates a cascade of neuronal-mediated events culminating in MC activation and TRPV overexpression. These phenomena are consequences of an impaired release of endogenous PEA. PEA might be regarded as an attractive therapeutic strategy for the treatment of FD.

Duodenal acidification induces gastric relaxation and alters epithelial barrier function by a mast cell independent mechanism.

Duodenal hyperpermeability and low-grade inflammation in functional dyspepsia is potentially related to duodenal acid exposure. We aimed to evaluate in healthy volunteers the involvement of mast cell activation on the duodenogastric reflex and epithelial integrity during duodenal acidification. This study consisted of 2 parts: (1) Duodenal infusion of acid or saline during thirty minutes in a randomized, double-blind cross-over manner with measurement of intragastric pressure (IGP) using high resolution manometry and collection of duodenal biopsies to measure epithelial barrier function and the expression of cell-to-cell adhesion proteins. Mast cells and eosinophils were counted and activation and degranulation status were assessed. (2) Oral treatment with placebo or mast cell stabilizer disodiumcromoglycate (DSCG) prior to duodenal perfusion with acid, followed by the procedures described above. Compared with saline, acidification resulted in lower IGP (P < 0.01), increased duodenal permeability (P < 0.01) and lower protein expression of claudin-3 (P < 0.001). Protein expression of tryptase (P < 0.001) was increased after acid perfusion. Nevertheless, an ultrastructural examination did not reveal degranulation of mast cells. DSCG did not modify the drop in IGP and barrier dysfunction induced by acid. Duodenal acidification activates an inhibitory duodenogastric motor reflex and, impairs epithelial integrity in healthy volunteers. However, these acid mediated effects occur independently from mast cell activation.

Molecular Dynamics Simulations on Interindividual Variability of Intestinal Fluids: Impact on Drug Solubilization.

Efficient delivery of oral drugs is dependent on their solubility in human intestinal fluid, a complex and dynamic fluid that contains colloidal structures composed of small molecules. These structures solubilize poorly water-soluble compounds, increasing their apparent solubility, and possibly their bioavailability. In this study, we conducted coarse-grained molecular dynamics simulations with data from duodenal fluid samples previously acquired from five healthy volunteers. In these simulations, we observed the self-assembly of mixed micelles of bile salts, phospholipids, and free fatty acids. The micelles were ellipsoids with a size range of 4-7 nm. Next, we investigated micelle affinities of three model drugs. The affinities in our simulation showed the same trend as literature values for the solubility enhancement of drugs in human intestinal fluids. This type of simulations is useful for studies of events and interactions taking place in the small intestinal fluid.

Therapeutic effect of Lactobacillus rhamnosus SHA113 on intestinal infection by multi-drug-resistant Staphylococcus aureus and its underlying mechanisms.

Staphylococcus aureus, especially multi-drug-resistant (MDR) pathogenic S. aureus, poses a severe threat to food safety and human health. Probiotics offer promising potential for the control of MDR pathogens because of their safe and biofunctional properties. This study shows that Lactobacillus rhamnosus SHA113, a strain isolated from the milk of healthy women, could efficiently inhibit MDR S. aureus both in vitro and in vivo. In vitro, L. rhamnosus efficiently inhibited and even killed drug resistant and drug sensitive S. aureus strains. In vivo experiments showed that SHA113 could efficiently decrease the number of S. aureus cells, inhibit the expression of inflammatory factors TNF-α and IL-6, and restore the level of white cells and neutrophils in the blood. SHA113 could also efficiently repair damage of the intestinal barrier and other functions impaired by S. aureus infection. This was indicated by a change of intestinal villi length and structure, and an up-regulated expression of tight junction proteins ZO-1 and occludin. SHA113 also restored the structural damage of immune organs, such as the enlargement of the spleen and the increased level of inflammatory cytokines caused by S. aureus infection. More importantly, L. rhamnosus SHA113 showed more effective inhibitory and therapeutic effects on MDR S. aureus strain ZBQ006 than on drug sensitive S. aureus strain 29213. These results illustrated that L. rhamnosus SHA113 has great potential for the treatment of MDR S. aureus contamination as food control and for therapeutic treatment.

Differential regulation of claudin-2 and claudin-15 expression in children and adults with malabsorptive disease.

Intestinal Na+-nutrient cotransport depends on claudin-2 and claudin-15 mediated Na+ recycling. Expression of these proteins is coordinately regulated during postnatal development. While expression of claudin-2 and claudin-15 has been studied in inflammatory bowel disease (IBD) and celiac disease (CD), it has not been assessed in other malabsorptive diseases, and no reports have compared expression in children and adults. We used quantitative immunofluorescence microscopy to assess claudin-2 and claudin-15 expression in duodenal biopsies from children and adults with malabsorptive disease and healthy controls. Consistent with previous work in rodents, claudin-2 expression in healthy children was markedly greater, and claudin-15 expression was less, than that in adults. Claudin-2 expression was increased in adults with CD and downregulated in children with graft-versus-host disease (GVHD). In contrast, claudin-15 expression was reduced in adults with GVHD and common variable immunodeficiency (CVID). These data show that one of the two Na+/water pore-forming claudins is upregulated in CD and downregulated in GVHD and CVID. The specific claudin whose expression changes, however, reflects the age of the patient (child or adult). We conclude that contributions of claudin-2 and claudin-15 to pathophysiology of and responses to diarrhea in children and adults with GVHD and CVID differ from those in CD and IBD.

A lower duodenal immune response is associated with an increase of insulin resistance in patients with morbid obesity.

OBJECTIVE: The intestinal immune response could play an important role in obesity-related comorbidities. We aim to study the profile of duodenal cytokines and chemokines in patients with morbid obesity (MO), its relation with insulin resistance (IR) and the intake of metformin, and with the evolution of MO after sleeve gastrectomy (SG). RESEARCH DESIGN AND METHODS: Duodenal levels of 24 cytokines and 9 chemokines were analyzed in 14 nonobese and in 54 MO who underwent SG: with lower IR (MO-lower-IR), with higher IR (MO-higher-IR), and with type 2 diabetes treated with metformin (MO-metf-T2DM). RESULTS: MO-lower-IR had higher levels of cytokines related to Th1, Th2, Th9, Th17, Th22, M1 macrophages, and chemokines involved in the recruitment of macrophages and T-lymphocytes (p < 0.05), and total (CD68 expression) and M1 macrophages (ITGAX expression) (p < 0.05) when compared with nonobese patients, but with a decrease in M2 macrophages (MRC1 expression) (p < 0.05). In MO-higher-IR, these chemokines and cytokines decreased and were similar to those found in nonobese patients. In MO-metf-T2DM, only IL-4 (Th2) and IL-22 (Th22) increased their levels with regard to MO-higher-IR (p < 0.05). In MO-higher-IR and MO-metf-T2DM, there was a decrease of CD68 expression (p < 0.05) while ITGAX and MRC1 were similar with regard to MO-lower-IR. We found an association between CXCL8, TNFß and IL-2 with the evolution of body mass index (BMI) after SG (p < 0.05). CONCLUSIONS: There is an association between a higher IR and a lower duodenal immune response in MO, with a slight increase in those patients with metformin treatment. Intestinal immune response could be involved in the evolution of BMI after SG.

Determination of the changes on the small intestine of pregnant mice by histological, enzyme histochemical, and immunohistochemical methods.

BACKGROUND/AIMS: The aim of the present study was to determine the changes on the small intestine in mice during pregnancy using histological, enzyme histochemical, and immunohistochemical methods. MATERIALS AND METHODS: A total of 24 Swiss albino female mice were divided as non-pregnant/control, first week, second week, and third week of pregnancy (n=6). Tissue samples obtained from the duodenum, jejunum, and ileum were processed by means of routine histological techniques and stained with Crossmon's triple staining. Alkaline phosphatase (ALP) was demonstrated with the simultaneous azo-coupling method. Proliferating cell nuclear antigen (PCNA) was demonstrated with the streptavidin-biotin-peroxidase complex method. The numerical data of the parameters were obtained and analyzed statistically. RESULTS: Villus height, villus width, and the rate of villus height/crypt depth were decreased in the duodenum, jejunum, and ileum in the last week of pregnancy compared with the control group. Changes in the crypt depth of the duodenum, jejunum, and ileum in pregnancy were found. The muscle width increased in pregnancy. It was identified that the ALP reactivity statistically significantly increased in the duodenum, jejunum, and ileum in pregnancy. The percentage of PCNA-positive cells in the duodenum, jejunum, and ileum increased in the first and second weeks of pregnancy, whereas it decreased in the third week of pregnancy compared with non-pregnant control animals. CONCLUSION: In conclusion, villus parameters, ALP reactivity, and percentage of PCNA-positive cells in the small intestine were affected during pregnancy.

Combined Analysis of Methylation and Gene Expression Profiles in Separate Compartments of Small Bowel Mucosa Identified Celiac Disease Patients' Signatures.

By GWAS studies on celiac disease, gene expression was studied at the level of the whole intestinal mucosa, composed by two different compartments: epithelium and lamina propria. Our aim is to analyse the gene-expression and DNA methylation of candidate genes in each of these compartments. Epithelium was separated from lamina propria in biopsies of CeD patients and CTRs using magnetic beads. Gene-expression was analysed by RT-PC; methylation analysis required bisulfite conversion and NGS. Reverse modulation of gene-expression and methylation in the same cellular compartment was observed for the IL21 and SH2B3 genes in CeD patients relative to CTRs. Bioinformatics analysis highlighted the regulatory elements in the genomic region of SH2B3 that altered methylation levels. The cREL and TNFAIP3 genes showed methylation patterns that were significantly different between CeD patients and CTRs. In CeD, the genes linked to inflammatory processes are up-regulated, whereas the genes involved in the cell adhesion/integrity of the intestinal barrier are down-regulated. These findings suggest a correlation between gene-expression and methylation profile for the IL21 and SH2B3 genes. We identified a "gene-expression phenotype" of CeD and showed that the abnormal response to dietary antigens in CeD might be related not to abnormalities of gene structure but to the regulation of molecular pathways.

Maternal high-fat diet exposure during gestation, lactation, or gestation and lactation differentially affects intestinal morphology and proteome of neonatal mice.

Offspring nutrition depends on the mother during gestation and lactation; thus, maternal nutrition and metabolism can affect their development. We hypothesized that maternal exposure to high-fat (HF) diet affects neonate's gastrointestinal tract development. Our objective was to determine the effect of maternal HF diet during gestation and lactation on neonate's duodenum histomorphology and proteome. Female mice were fed either a control (C, 10% kcal fat) or an HF (60% kcal fat) diet for 4 weeks and bred. On postnatal day 2, half the pups were cross-fostered to dams fed on different diet, creating 4 treatments: C-C, C-HF, HF-C, and HF-HF, indicating maternal diet during gestation-lactation, respectively. On postnatal day 12, pups' duodenum was excised and prepared for histology and liquid chromatography-tandem mass spectrometry analysis of proteome. Villi were significantly longer in HF-HF pups, and crypt cell proliferation rate was not different among treatments. Between C-C and HF-HF, HF-C, or C-HF, 812, 601, or 894 proteins were differentially expressed (Tukey adjusted P < .05), respectively. Functional analysis clustered proteins upregulated in HF-HF vs C-C in fat digestion and absorption, extracellular matrix, cell adhesion, immune response, oxidation-reduction processes, phagocytosis, and transport categories. Proteins downregulated were classified as RNA splicing, translation, protein folding, endocytosis, and transport. There was evidence for a carryover effect of exposure to HF diet during gestation to the postnatal period. Alterations in proteome relative to HF exposure potentially reflect long-term changes in the functioning of the duodenum.

Low intake of digestible carbohydrates ameliorates duodenal absorption of carbohydrates in mice with glucose metabolism disorders induced by artificial sweeteners.

BACKGROUND: Long-term artificial sweetener consumption has been reported to induce glucose intolerance, and the intestinal microbiota seems as an important target. While the impacts of artificial sweeteners on energy balance remain controversial, this work aimed to evaluate the protective effects in mice of a low digestible carbohydrate (LDC) diet on plasma glucose, plasma fasting insulin, sweet taste receptors, glucose transporters, and absorption of carbohydrates, together with consumption of acesulfame potassium (AK) or saccharin (SAC). RESULTS: Artificial sweetener was administered to mice for 12 weeks to induce glucose metabolism disorders; mice were treated with an LDC diet for the final 6 weeks. The experimental groups were treated with an LDC diet that had the same energy as the normal-diet group. Prolonged administration of artificial sweeteners led to metabolic dysfunction, characterized by significantly increased plasma glucose, insulin resistance, sweet taste receptors, glucose transporters, and absorption of carbohydrates. Treatment with an LDC diet positively modulated these altered parameters, suggesting overall beneficial effects of an LDC diet on detrimental changes associated with artificial sweeteners. CONCLUSIONS: Reducing digestible carbohydrates in the diet can significantly reduce the absorption of carbohydrates and improve glucose metabolism disorders caused by dietary factors. These effects may be due to the fact that reducing the amount of digestible carbohydrates in the feed can reduce the number of intestinal sweet receptors induced by exposure to artificial sweeteners. © 2019 Society of Chemical Industry.

Intranasal immunization with recombinant Trichinella spiralis serine protease elicits protective immunity in BALB/c mice.

The aim of this study was to observe the intestinal mucosal/systemic responses triggered by intranasal vaccination using recombinant Trichinella spiralis serine protease (rTsSP) and its capacity to elicit immune protection against larva challenge in a murine model. rTsSP coupled with cholera toxin B subunit (CTB) was used to vaccinate mice via intranasal route. The results revealed that intranasal vaccination with rTsSP plus CTB elicited significantly intestinal local sIgA response and a TsSP-specific systemic antibody response in vaccinated mice. Furthermore, more goblet cells/acidic mucins and IgA-secreting cells were observed in jejunum from vaccinated mice. Anti-rTsSP immune serum strongly recognized the cuticle of various worm stages (muscle larva, intestinal infective larva and adult worm). The level of IFN-γ, IL-4 and IL-10 of rTsSP-vaccinated mice was significantly elevated relative to CTB and PBS control groups. The vaccinated mice exhibited a 71.10% adult reduction at 9 days pi and a 62.10% muscle larva reduction at 42 days pi following larva challenge. Additionally, vaccination with rTsSP also dampened intestinal T. spiralis development and decreased the female fecundity. Our results showed that intranasal vaccination using rTsSP adjuvanted with CTB triggered significantly local sIgA response and systemic concurrent Th1/Th2 response that induced an obvious protection against Trichinella infection.

Variants in ABCG8 and TRAF3 genes confer risk for gallstone disease in admixed Latinos with Mapuche Native American ancestry.

Latin Americans and Chilean Amerindians have the highest prevalence of gallstone disease (GSD) and gallbladder cancer (GBC) in the world. A handful of loci have been associated with GSD in populations of predominantly European ancestry, however, they only explain a small portion of the genetic component of the disease. Here, we performed a genome-wide association study (GWAS) for GSD in 1,095 admixed Chilean Latinos with Mapuche Native American ancestry. Disease status was assessed by cholecystectomy or abdominal ultrasonography. Top-10 candidate variants surpassing the suggestive cutoff of P < 1 × 10-5 in the discovery cohort were genotyped in an independent replication sample composed of 1,643 individuals. Variants with positive replication were further examined in two European GSD populations and a Chilean GBC cohort. We consistently replicated the association of ABCG8 gene with GSD (rs11887534, P = 3.24 × 10-8, OR = 1.74) and identified TRAF3 (rs12882491, P = 1.11 × 10-7, OR = 1.40) as a novel candidate gene for the disease in admixed Chilean Latinos. ABCG8 and TRAF3 variants also conferred risk to GBC. Gene expression analyses indicated that TRAF3 was significantly decreased in gallbladder (P = 0.015) and duodenal mucosa (P = 0.001) of GSD individuals compared to healthy controls, where according to GTEx data in the small intestine, the presence of the risk allele contributes to the observed effect. We conclude that ABCG8 and TRAF3 genes are associated with GSD and GBC in admixed Latinos and that decreased TRAF3 levels could enhance gallbladder inflammation as is observed in GSD and GSD-associated GBC.

Effects of chemical speciation on the bioaccessibility of zinc in spiked and smelter-affected soils.

Previous studies have suggested that understanding soil metal speciation, rather than relying solely on total metal content, can improve the accuracy and utility of contaminated site risk assessments. Because soil properties and reaction time can alter metal speciation, speciation should influence metal bioaccessibility. For example, under gastrointestinal conditions, it is expected that metal species will differ in bioaccessibility depending on their stability in acidic pH environments. We studied the links between metal speciation and bioaccessibility. A combination of synchrotron-based X-ray diffraction and X-ray absorption near edge structure (XANES) was used to identify the zinc (Zn) speciation in spiked and smelter-affected soils. After conducting in vitro digestion tests on the soil samples, XANES and linear combination fitting were carried out on the residual pellets to identify the species of Zn that remained after digesting the soils in the simulated gastric and duodenal fluids. The metal species that were not present in the residual pellets were inferred to have been dissolved and, thus, more bioaccessible. Sphalerite (ZnS), ZnO, and outer-sphere Zn contributed more to Zn bioaccessibility than franklinite (ZnFe2 O4 ) and Zn incorporated into a hydroxy interlayer mineral (Zn-HIM). The bioaccessibility of Zn-aluminum layered double hydroxides (Zn-Al-LDH) was found to be inversely proportional to its residence time in soil. It was also observed that the relatively high pH of the duodenum favors metal reprecipitation and readsorption, leading to a reduction in bioaccessible metal concentration. These results imply that metal speciation mainly controls metal bioaccessibility. Environ Toxicol Chem 2019;38:448-459. © 2018 SETAC.

Duodenal Niemann-Pick C1-like 1 expression was negatively correlated with liver X receptor expression in nonalcoholic fatty liver disease.

BACKGROUND/AIMS: Intestinal cholesterol absorption includes intestinal Niemann-Pick C1-like 1 (NPC1L1) and is an important target pathway in nonalcoholic fatty liver disease (NAFLD). We investigated the expression of NPC1L1 and its correlation with liver X receptor (LXR) expression in peripheral mononuclear (PMN) cells in patients with NAFLD. METHODS: We evaluated intestinal expression of NPC1L1 in 25 NAFLD patients and 28 healthy controls. We calculated the mRNA expression levels of LXR and farnesoid X receptor (FXR), which are master players of cholesterol metabolism in PMN cells. The protein expression of ABCA1, ABCG5/8, NPC1L1, SREBP, LXR, FXR, and CD36 was measured on tissue samples from the duodenum and ileum. RESULTS: The expression of LXR (p = 0.01) and FXR (p = 0.03) in PMN cells was increased in the NAFLD group compared to the control group. Duodenal NPC1L1 decreased in the NAFLD group compared to the healthy controls (3.38 ± 1.4 vs. 2.42 ± 1.2, p = 0.05). NPC1L1 expression in the duodenum was negatively correlated with LXR expression in PMN cells. Expression of LXR and FXR in the ileum was also negatively correlated with the expression of LXR in PMN cells. CONCLUSION: Duodenal NPC1L1 expression was decreased in NAFLD and was negatively correlated with LXR expression in PMN cells.

Active ß-Catenin Signaling in the Small Intestine of Humans During Infancy.

BACKGROUND: Wnt-ß-catenin signaling is essential for homeostasis of intestinal stem cells in mice and is thought to promote intestinal crypt fission. AIMS: The aim of this study was to investigate Wnt-ß-catenin signaling in intestinal crypts of human infants. METHODS: Duodenal biopsies from nine infants (mean, range 0.9 years, 0.3-2 years) and 11 adults (mean, range 43 years, 34-71 years) were collected endoscopically. Active ß-catenin signaling was assessed by cytoplasmic and nuclear ß-catenin, nuclear c-Myc, and cytoplasmic Axin-2 expression in the base of crypts. Tissues were stained by an immunoperoxidase staining technique and quantified as pixel energy using cumulative signal analysis. Data were expressed as mean ± SD and significance assessed by Student's t test. RESULTS: Crypt fission was significantly higher in infants compared to adults (16 ± 8.6% versus 0.7 ± 0.6%, respectively, p < 0.0001). Expression of cytoplasmic and nuclear ß-catenin was 1.8-fold (p < 0.0001) and 2.9-fold (p < 0.0001) higher in infants, respectively, while cytoplasmic Axin-2 was 3.1-fold (p < 0.0001) increased in infants. c-Myc expression was not significantly different between infants and adults. Expression was absent in Paneth cells but present in the transit amplifying zone of crypts. Crypt base columnar cells, which were intercalated between Paneth cells, expressed c-Myc. CONCLUSIONS: Wnt-ß-catenin signaling was active in crypt base columnar cells (i.e., intestinal stem cells) in human infants. This signaling could promote crypt fission during infancy. Wnt-ß-catenin signaling likely acts in concert with other pathways to promote postnatal growth.

Intestinal mucosa develops in a sex-dependent manner in Japanese quail (Coturnix japonica) fed Saccharomyces cerevisiae.

1. The aim of study was to investigate whether the impact of the yeast Saccharomyces cerevisiae on the histological structure of the intestine, innervation of the small intestine wall, and basal biochemical serum parameters in Japanese quail was sex dependent. 2. One-day-old healthy male and female Japanese quail were fed either a basal diet containing no yeast (control group) or the basal diet plus 1.5% (15 g/kg of diet) of yeast (S. cerevisiae inactivated by drying). Samples from the duodenum and jejunum were taken from each bird at the age of 42 days. Blood samples were collected at this age and the concentrations of glucose, total protein, creatinine, uric acid, lipid profile (total cholesterol, low density lipoproteins (LDL), high density lipoproteins (HDL) and triacylglycerols (TG)), alanine aminotransferase (ALAT), aspartate aminotransferase (AspAT), lactate dehydrogenase (LDH), amylase (AMY), calcium, phosphorus and iron were determined. 3. Female quail fed diets supplemented with yeast had significantly lower total cholesterol and amylase activity than the control females. The concentration of HDL was higher in the male quail than in the females, irrespective of the treatment. An opposite effect was observed in LDL. The diet treatments influenced the activity of AspAT, which was significantly less in the male quail fed diets with 1.5% yeast. 4. Supplementation with S. cerevisiae increased the myenteron, submucosa and mucosa thickness, villus length and thickness and size of absorptive surface, while the number of villi and enterocytes were decreased in the duodenum in males. Female quail showed an increased absorptive surface in the jejunum. The Meissner (submucosal) plexuses were influenced by the feeding and sex to a greater extent than the Auerbach plexus (in the muscularis propria). 5. The results demonstrated that S. cerevisiae (1.5%) in the diet caused significant positive effects in Japanese quail, exerting an effect on the morphology of the small intestine in a sex-dependent manner.