Expression In Duodenum Research Articles

Responses of Intestinal Antioxidant Capacity, Morphology, Barrier Function, Immunity, and Microbial Diversity to Chlorogenic Acid in Late-Peak Laying Hens.

This study examined the influence of chlorogenic acid (CGA) on gut antioxidant status, morphology, barrier function, immunity, and cecal microbiota in late-peak laying hens. A total of 240 Hy-Line Brown hens, aged 43 weeks, were randomly assigned to four groups, the basal diet +0, 400, 600, and 800 mg/kg CGA, for 12 weeks. The results revealed that CGA significantly reduced ileal H2O2 and malondialdehyde levels; increased duodenal height, ileal villus height, and villus height-to-crypt depth ratio; while decreasing jejunal crypt depth. The 600 and 800 mg/kg CGA significantly upregulated the duodenal, jejunal, and ileal ZO-1 and occludin gene expression; increased IgG levels in serum and ileum; and upregulated ileal IgA gene expression. The 600 mg/kg CGA significantly upregulated CD3D and CD4 gene expression, while downregulating IL-1β gene expression in duodenum, jejunum, and ileum. Moreover, CGA changed the gut microbiota structure. The SCFA-producing bacteria unclassified_f__Peptostreptococcaceae, unclassified_f_Oscillospiraceae, Pseudoflavonifractor, Lachnospiraceae_FCS020_group, Oscillospira, Elusimicrobium, Eubacterium_ventriosum_group, Intestinimonas, and norank_f_Coriobacteriales_Incertae_Sedis were significantly enriched in the 400, 600, and/or 800 mg/kg CGA groups. The bacteria Lactobacillus, Bacillus, and Akkermansia were significantly enriched in the 600 mg/kg CGA group. Conclusively, dietary CGA (600-800 mg/kg) improved intestinal antioxidant status, morphology, barrier and immune function, and beneficial microbiota growth in late-peak laying hens.

Altered Bioavailability and Pharmacokinetics in Crohn's Disease: Capturing Systems Parameters for PBPK to Assist with Predicting the Fate of Orally Administered Drugs.

Backgrond and ObjectiveCrohn’s disease (CD) is a chronic inflammatory bowel disease that affects a wide age range. Hence, CD patients receive a variety of drugs over their life beyond those used for CD itself. The changes to the integrity of the intestine and its drug metabolising enzymes and transporters (DMETs) can alter the oral bioavailability of drugs. However, there are other changes in systems parameters determining the fate of drugs in CD, and understanding these is essential for dose adjustment in patients with CD.MethodsThe current analysis gathered all the available clinical data on the kinetics of drugs in CD (by March 2021), focusing on orally administered small molecule drugs. A meta-analysis of the systems parameters affecting oral drug pharmacokinetics was conducted. The systems information gathered on intestine, liver and blood proteins and other physiological parameters was incorporated into a physiologically based pharmacokinetic (PBPK) platform to create a virtual population of CD patients, with a view for guiding dose adjustment in the absence of clinical data in CD.ResultsThere were no uniform trends in the reported changes in reported oral bioavailability. The nature of the drug as well as the formulation affected the direction and magnitude of variation in kinetics in CD patients relative to healthy volunteers. Even for the same drug, the reported changes in exposure varied, possibly due to a lack of distinction between the activity states of CD. The highest alteration was seen with S-verapamil and midazolam, 8.7- and 5.3-fold greater exposure, respectively, in active CD patients relative to healthy volunteers. Only one report was available on liver DMETs in CD, and indicated reduced CYP3A4 activity. In a number of reports, mRNA expression of DMETs in the ileum and colon of CD patients was measured, focussing on P-glycoprotein (p-gp) transporter and CYP3A4 enzyme, and showed contradictory results. No data were available on protein expression in duodenum and jejunum despite their dominant role in oral drug absorption.ConclusionThere are currently inadequate dedicated clinical or quantitative proteomic studies in CD to enable predictive PBPK models with high confidence and adequate verification. The PBPK models for CD with the available systems parameters were able to capture the major physiological influencers and the gaps to be filled by future research. Quantification of DMETs in the intestine and the liver in CD is warranted, alongside well-defined clinical drug disposition studies with a number of index drugs as biomarkers of changes in DMETs in these patients, to avoid large-scale dedicated studies for every drug to determine the effects of disease on the drug’s metabolism and disposition and the consequential safety and therapeutic concerns.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40262-022-01169-4.

Transcutaneous auricular vagus nerve stimulation promotes gastric motility by up-rgulating α7nAChR and suppressing NF-κB p65 expression in duodenum in rats with functional dyspepsia

To study the effect of transcutaneous auricular vagus nerve stimulation (taVNS) on gastric sensitivity and motility in rats with functional dyspepsia (FD), so as to explore its underlying mechanism in improving FD. A total of 48 young SD rats were randomly divided into control (n=10), model (n=9), taVNS (n=9), subdiaphragmatic vagus nerve stimulation (SDVNS, n=9) and sham SDVNS (n=7) groups. The FD model was established by gavage of 0.1% iodoa-cetamide+2% glucose, once daily for 6 days. Rats in the taVNS group received taVNS (0.5 mA) of optopoint "Heart" and "Stomach" for 30 min, once daily for 14 days, while rats in the SDVNS group received subdiaphragmatic vagus nerve stimulation through the implanted electrode, and those of the sham SDVNS group received only application of the same electrodes without electrical stimulation. Electromyogram (EMG) of the cervical trapezius muscle (reflecting gastric sensitivity) was recorded before and after intragastric expansion via an air ballon and the gastric emptying rate was calculated for assessing the gastric motility. The contents of acetylcholine (ACh), nicotinic acetylcholine receptor α7 subunit (α7nAChR), interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in the duodenum tissue were detected by enzyme-linked immunosorbent assay (ELISA). The expression of nuclear factor kappa B (NF-κB) p65 in the duodenum tissue was determined by Western blot. In comparison with the control group, the EMG change rate at intragastric pressure levels of 40, 60 and 80 mm Hg, expression of NF-κB p65 protein, and contents of IL-6, IL-1β and TNF-α were significantly increased (P<0.05,P<0.01, P<0.001), while the gastric emptying rate, ACh and α7nAChR contents considerably decreased (P<0.05, P<0.001) in the model group. After interventions, the EMG change rate, contents of IL-6, IL-1β and TNF-α, and expression of NF-κB p65 were notably decreased (P<0.05, P<0.01, P<0.001), and the gastric emptying rate, ACh and α7nAChR contents obviously increased (P<0.05, P<0.001) in both taVNS and SDVNS groups relevant to the model group. In comparison with the sham SDVNS group, the EMG change rate, contents of IL-6, IL-1β and TNF-α, and expression of NF-κB p65 were notably decreased (P<0.01, P<0.05,P<0.001), and the gastric emptying rate, ACh and α7nAChR contents obviously increased (P<0.01, P<0.001) in the both SDVNS and taVNS groups. taVNS can reduce gastric sensitivity and promote gastric emptying in FD model rats, which may be closely related to its functions in up-regulating ACh and α7nAChR contents and inhibiting the activation of NF-κB p65 signaling in the duodenum.

Eugenol alleviated nonalcoholic fatty liver disease in rat via a gut-brain-liver axis involving glucagon-like Peptide-1

Eugenol, an active ingredient of many medicinal aromatic plants, has been proved to have the hypolipidemic effect, but its potential mechanism of action is still unknown. This study aimed to investigate whether eugenol regulates liver lipid accumulation in high-fat diet (HFD) induced nonalcoholic fatty liver disease (NAFLD) rats via the gut-brain-liver axis involving glucagon-like peptide-1 (GLP-1). Hepatic vagotomy was performed in NAFLD rats to determine the role of eugenol in regulating hepatic lipid accumulation via vagus nerve. The results showed that after eight weeks of eugenol administration in NAFLD rats, serum total cholesterol (TC), triglyceride (TG) and hepatic TG decreased. However, eugenol showed no significant effect on the increased food intakes and weight gain caused by the HFD. Eugenol promoted the secretion of GLP-1 into the blood, increased GLP-1 receptor (GLP-1R) expression in the duodenum, liver, arcuate nucleus (ARC) and paraventricular nucleus (PVN), increased c-fos expression in the nucleus tractus solitarii (NTS), and promoted ZO-1 and occludin expression in duodenum. Furthermore, steatosis and lipid accumulation were significantly alleviated. Hepatic vagotomy partially attenuated the improvement of eugenol in hepatic lipid accumulation in NAFLD rats. In conclusion, eugenol regulates hepatic lipid metabolism via a gut-brain-liver axis involving in GLP-1, providing a new strategy for the treatment of NAFLD.

Polysaccharides derived from Astragalus membranaceus and Glycyrrhiza uralensis improve growth performance of broilers by enhancing intestinal health and modulating gut microbiota

This study was conducted to investigate the effects of dietary supplementation of polysaccharides derived from Astragalus membranaceus and Glycyrrhiza uralensis on growth performance, intestinal health, and gut microbiota composition in broilers. A total of 480 one-day-old male Arbor Acres broilers were randomly divided into 4 treatments with 6 replicates comprising 20 broilers each. Treatments included: basal diet without antibiotics (CON); basal diet supplemented with 500 mg/kg terramycin calcium (ANT); basal diet supplemented with 300 mg/kg Astragalus membranaceus polysaccharides (APS); and basal diet supplemented with 150 mg/kg Glycyrrhiza uralensis polysaccharides (GPS). The results showed that ANT, AP,S and GPS supplementation significantly increased average daily gain (ADG) and decreased feed conversion ratio (FCR) of broilers from 1 to 42 d of age. At 42 d, serum immunoglobulin A (IgA), immunoglobulin M (IgM) and immunoglobulin G (IgG) levels of the APS and GPS group were notably higher than those of the CON group, while serum levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) as well as diamine oxidase (DAO) activity in the APS and GPS group were obviously decreased. Moreover, diets supplemented with APS and GPS could significantly increase villus height (VH) and the ratio of villus height to crypt depth (VH/CD) and remarkably upregulated occludin, claudin-1 and mucin-2 (MUC2) mRNA expression in duodenum, jejunum, and ileum of broilers. In addition, 16S rRNA gene sequencing revealed that APS and GPS supplementation altered cecal microbial diversity and composition in broilers. Higher Shannon index was observed in the APS and GPS group compared with the CON group, while GPS supplementation could also increase Chao1 index and Observed species. The result of Principal coordinate analysis (PCoA) showed that microbial community in the CON, ANT, APS, and GPS group clustered separately. Notably, both APS and GPS supplementation significantly decreased the abundance of Bacteroidetes, Bacteroides, Faecalibacterium, Desulfovibrio, and Butyricicoccus, while increased the abundance of Firmicutes, Prevotella, Parabacteroides, Ruminococcus, and Alistipes. The correlation analysis showed that the changes in cecal microbial composition induced by dietary APS and GPS supplementation were closely associated with the alteration of the phenotype of broilers including ADG, FCR, TNF-α, IL-1β, IL-6, IgA, IgG, DAO, Occludin, Claudin-1, ZO-1, and MUC2. In conclusion, polysaccharides derived from Astragalus membranaceus and Glycyrrhiza uralensis could improve growth performance of broilers by enhancing intestinal health and modulating gut microbiota.

Effects of bioactive peptides derived from cottonseed meal solid-state fermentation on the growth, metabolism, and immunity of yellow-feathered broilers.

This study investigated the effects of bioactive peptides derived from solid-state fermentation of cottonseed meal on the growth performance, apparent dietary digestibility, serum biochemical parameters, protein metabolism, antioxidant activity, and immunity in yellow-feathered broilers. A total of two hundred forty 21-days-old male broilers were randomly divided into four groups with six replicates per group. The control group received a basal diet and three experimental groups were fed diets with 1%, 2%, and 3% cottonseed meal bioactive peptides (CSBP) replacing equivalent protein of cottonseed meal in basic diet. Dietary supplementation of 2% and 3% CSBP increased the average daily weight gain, crude protein digestibility, total serum protein, and immunoglobulin (Ig) G contents in serum (P < 0.05). The 3% CSBP increased albumin, total antioxidant capacity, spleen weight/bodyweight, interleukin-6, and IgM, while reducing the feed to gain ratio, total cholesterol, urea nitrogen, total superoxide dismutase, glutathione peroxidase, and malondialdehyde contents in serum (P < 0.05). The 2% CSBP diet increased PepT1 expression in duodenum, jejunum, and ileum (P < 0.05). The 1%, 2%, and 3% CSBP diets increased S6kinase-polypeptide-1 and inositol-3-hydroxylase expression in chest and leg muscles (P < 0.05). The CSBP addition in diets can improve growth performance, nutrient digestibility, protein metabolism, antioxidant, and immune capabilities of yellow-feathered broilers.

Exploring the effectiveness of in ovo feeding of vitamin C based on the embryonic vitamin C synthesis and absorption in broiler chickens

BackgroundMany researches about in ovo feeding (IOF) of vitamin C (VC) are gradually carried out to explore physiological development in chicken, but little studies focus on VC synthesis capacity of the embryo itself, the selection of injection site and the effectiveness of IOF of VC. This study aims to explore the above problems.ResultsKidney and yolk sac were the main organs for VC synthesis and L-gulonolactone oxidase (GLO) expression was lower during pre-hatch development than that during post-hatch development. Sodium-dependent vitamin C transporter 1 (SVCT1) expression was increased continuously in yolk sac from embryonic age 19 (E19) to post-hatch day 1 (D1) and in intestine (duodenum, jejunum and ileum) from E17 to D1. Plasma VC content was higher at D1 than that at D21 and D42. IOF of VC significantly reduced GLO expression in liver, kidney and yolk sac as well as SVCT1 expression in duodenum, jejunum and ileum, but increased the VC content in plasma, brain, kidney and liver. In addition, IOF of VC obviously reduced the embryonic morality and increased the hatchability under heat stress.ConclusionsThis study suggested that IOF of VC at E11 in yolk was effective for embryonic VC supplementation. These findings provide a theoretical reference about the method of embryonic VC supplementation and effective methodology on embryonic VC nutrition in broiler chickens.

Alterations on vitamin C synthesis and transportation and egg deposition induced by dietary vitamin C supplementation in Hy-Line Brown layer model.

In ovo feeding of vitamin C (VC) has positive effects on the growth performance, immune and antioxidant function in poultry, which indicates that increasing VC content in eggs may be of benefit. This study was to investigate the effects of dietary VC supplementation on VC synthesis and transportation and egg deposition. In Exp. 1, in order to select a suitable animal model, VC content was detected in different eggs from different layer species. Vitamin C content was lower in ISA Brown breeder eggs and Hy-Line Brown layer eggs (P < 0.05) then in Arbor Acres breeder eggs. In Exp. 2, a total of 24 Hy-Line Brown layers (42-week-old) were randomly divided into 3 treatments with 8 replicates and fed a basal diet with VC at 0, 200 and 400 mg/kg. Sodium-dependent VC transporter 1 and 2 (SVCT1 and SVCT2) expressions were higher in ileum than in duodenum and jejunum (P < 0.05). SVCT1 expression was higher but SVCT2 expression was lower in the magnum than in the ovary (P < 0.05). L-Gulonolactone oxidase (GLO) and SVCT1 expressions were higher but SVCT2 was lower in the kidney than in the liver (P < 0.05). Dietary VC supplementation at 400 mg/kg increased SVCT1 expression in duodenum, ovary and magnum, but decreased GLO and SVCT1 expression in liver (P < 0.05). Dietary VC supplementation at 200 and 400 mg/kg increased SVCT2 expression in duodenum, but decreased GLO and SVCT1 expression in kidney and SVCT2 expression in liver (P < 0.05). Dietary VC supplementation promoted VC absorption in duodenum and jejunum, but reduced endogenous VC synthesis in liver and kidney. Although dietary VC supplementation enhanced VC transportation in ovary and magnum, it did not increase VC deposition in produced eggs.

Differential gene expression in duodenum of colored broiler chicken divergently selected for residual feed intake.

Feed constitutes about 70% of the total expenditure of poultry production. Maximizing the feed efficiency in juvenile period is essential to achieve low production cost. The efficiency of feed utilization was measured by RFI (residual feed intake) by calculating the difference between an individual animal's observed and its expected feed intake. The expression of genes influencing low and high RFI is required to know the basic molecular mechanism influencing feed efficiency. The present study aimed to estimate the RFI (0-5week) in a population of indigenously developed colored broiler sire line chicken. The duodenum sample of high and low-RFI broiler chicken was used for microarray analysis. Duodenum exhibited 1030 differentially expressed genes after analysis. Out of total DEGs, 461 genes were downregulated and 569 were upregulated. The fold change of differentialllyexpressed genesvaries from - 162.6 to 1549.28. A subset of genes was validated by qRT-PCR and results were correlated well with microarray data. In functional annotation study of DEGs, 89 biological processes, 30 cellular components, and 29 molecular functions were identified. Study of the important differentially expressed genes and the related molecular pathways in the population may hold the potential for future breeding strategies for augmenting feed efficiency.

Effects of incubation and chick rearing on intestinal morphology, digestive enzyme activities, and mRNA expression of nutrient transporter genes in the pigeon (Columba livia) under artificial farming conditions

The present study investigated the changes in morphology, enzyme activities in the pancreas and mucosa, and nutrient transporter gene expression in the duodenum and jejunum in male and female pigeons during the incubation and chick-rearing periods. Forty-two pairs of White King pigeons with 2 fertile eggs per pair were randomly divided into 7 groups by different breeding stages. The crypt depth of the duodenum and jejunum reached the peak at day 1 (R1) and day 7 (R7) of chick rearing, respectively. The jejunum surface area increased to a maximum value at R1. Amylase activity in the pancreas decreased to the lowest value at R1, whereas trypsin and lipase activities peaked at 17 D of incubation (I17) and R7, respectively. In male pigeons, mucosal Na+-K+-ATPase activity in the duodenum and jejunum was the highest at R15 and it was at I17 in female pigeons. Jejunum sucrose activity in female pigeons was higher at I4 than that at I17 (P < 0.05). The gene expression of FAT/CD36 and I-FABP in the duodenum gradually increased and then declined in the late chick-rearing period. SGLT1 in the jejunum decreased to a lower level at I17 and R25 in male pigeons (P < 0.05). GLUT2 expression in female duodenum and male jejunum decreased to a lower value at I17 compared with that at R15 (P < 0.05). In the late of incubation (from I10 to I17), expression of duodenum CAT1, B0AT1, and PepT1 and jejunum CAT1, ASCT1, and PepT1 in female pigeons was significantly reduced (P < 0.05), whereas opposite results were found in male jejunum CAT1 and duodenum ASCT1. In conclusion, variations of intestinal morphology, activities of pancreatic and mucosal enzymes, and gene expression of nutrient transporters during incubation and chick-rearing periods, underlying potential changes of digestive and absorptive function and intestinal adaptation with sexual effects, may represent a complicated response to stimuli of different breeding stages.

Tributyrin differentially regulates inflammatory markers and modulates goblet cells number along the intestinal tract segments of weaning pigs

Butyric acid is widely used in pig production as feed additive to improve growth performance at weaning, based on its intestinal health-promoting action. The aim of this study was to evaluate the intestinal architecture and expression of inflammatory cytokines and tight junctions (TJ) markers in weaning piglets fed with tributyrin, either free or microencapsulated, as dietary source of butyric acid. One hundred and eight weaned piglets were divided into pens (4 piglets/pen, n = 9) and received either a basal diet (control) or the basal diet supplemented with tributyrin at 1750 mg/kg (f-TB) or its encapsulated form (m-TB) at 3800 mg/kg (providing 1750 mg/kg of tributyrin equally to f-TB). Growth performance was recorded until d21 when 7 pigs/group were euthanized to collect intestinal samples (duodenum, jejunum, ileum, colon) for histomorphology, cytokines, and TJ markers gene expression analysis. Data were analyzed with 1-way ANOVA. Growth performance was not affected. Compared with control pigs, m-TB pigs tended to induce deeper crypts in the duodenum (P = 0.09); goblet cell number tended to be reduced by f-TB treatment in duodenum villi (P = 0.09), by both f-TB and m-TB treatments in ileum villi (P = 0.06), and by m-TB treatment in colon crypts (P = 0.08). Compared with control animals, f-TB pigs showed higher tumor necrosis factor α (TNF-α) expression in duodenum (trend with P = 0.06), and higher interferon γ (IFN-γ) in the jejunum (P = 0.04), whereas in the colon m-TB pigs tended to down regulate IFN-γ (P = 0.06). Claudin-1 mRNA in the jejunum was reduced in m-TB group compared to control group (P = 0.05). Occludin mRNA in the ileum was reduced in both groups treated with tributyrin compared to control group (P < 0.01). In the colon occludin mRNA was downregulated both in f-TB and m-TB pigs compared to control pigs (P < 0.05).Overall, the supplementation of tributyrin in the diet reduced the mucous-secreting goblet cells in a tract-specific way and modulated the expression of inflammatory cytokines and TJ components along the intestinal tract of weaning piglets, without any negative effect on growth performance.

Expresión de enzimas relacionadas con la síntesis de poliaminas en mucosa intestinal de cerdos recién destetados

El estrés del destete puede alterar la salud intestinal de los cerdos; en esta etapa arginina se vuelve esencial ya que participa en la síntesis de poliaminas y éstas son importantes para mantener la viabilidad y proliferación celular en el epitelio intestinal. Se analizó la expresión de las enzimas arginino-succinato-sintasa (ASS) y espermina-espermidina-acetil-tranferasa (SSAT) relacionadas con la síntesis de arginina y poliaminas, en mucosa de intestino delgado de cerdos destetados. Veinticuatro cerdos destetados a los 28 días de edad, fueron sacrificados a los 0, 3, 7 y 14 días postdestete. Se colectaron muestras de mucosa de duodeno, yeyuno e íleon en las que se analizó la expresión relativa de ASS y SSAT. La expresión de ASS en duodeno se incrementó en el d3 (P

A Naringin- and Icariin-Contained Herbal Formula, Gushukang, Ameliorated Aged Osteoporosis of Aged Mice with High Calcium Intake.

Traditional herbal formula Gushukang (GSK) was clinically applied to treat primary osteoporosis and showed osteoprotective effect in ovariectomized rodent animals and regulatory action on calcium transporters. This study aimed to determine if GSK could ameliorate aged osteoporosis by modulating serum level of calciotropic hormones and improving calcium balance. 18-month-old male mice were orally administered with either GSK (0.38[Formula: see text]g/kg body weight) or calcitriol (1[Formula: see text][Formula: see text]g/kg body weight) combined with high calcium diet (HCD, 1.2% Ca) for 60 days. The aged mice fed with normal calcium diet (NCD, 0.6% Ca) were a negative control. Trabecular bone and cortical bone properties as well as calcium balance were determined. Treatment with GSK significantly increased 25(OH)D and 1,25-(OH)2D levels in serum, moreover, it markedly attenuated trabecular bone micro-architectural deteriorations and elevated trabecular bone mass as well as strengthened cortical bone mechanical properties shown by the increase in maximal bending load and elastic modulus. Calcium balance, including urinary Ca excretion, fecal Ca level and net calcium retention, was remarkably improved by GSK, which up-regulated TRPV6 expression in duodenum and TRPV5 expression in kidney and down-regulated claudin-14 expression in duodenum and kidney. Additionally, 1-OHase and 24-OHase expression was significantly decreased (vs. NCD group) and increased (vs. HCD group), respectively, in kidney of GSK- and calcitriol-treated mice. Taken together, this study demonstrated the ameliorative effects of Gushukang on aged osteoporosis by effectively stimulating vitamin D production and improving calcium balance of aged mice with high dietary calcium supplement.

Mucosal Monosaccharide Transporter Expression in Newborns With Jejunoileal Atresia and Along the Adult Intestine.

In newborn rodents, intestinal maturation involves delayed fructose transporter GLUT5 expression until weaning. In jejunoileal atresia (JIA), distal intestinal segments lack exposure to amniotic fluid-containing carbohydrates. We assessed in human newborns, the impact of intestinal maturation and obstruction on mucosal monosaccharide transporter expression. Samples were obtained from 10 newborns operated for small intestinal atresia and from 17 adults undergoing gastroduodenoscopy and/or ileocolonoscopy. mRNA expression of the transporters SGLT1, GLUT1, GLUT2, GLUT5, and GLUT7 was measured in neonate samples proximal and distal of the atresia as well as in adult duodenum, ileum, and colon. Protein expression and localization was assessed using immunofluorescence. Although mRNA expression of monosaccharide transporters did not significantly differ between newborn and adult samples, luminal fructose transporter GLUT5 protein was absent in 0- to 4-day-old neonates, but expressed in adults. The mRNA expression of the 5 tested monosaccharide transporters was unchanged distal from the JIA relative to proximal. Similarly, luminal sodium-dependent glucose transporter SGLT1 and basolateral GLUT2 were expressed proximal and distal to JIA as visualized by immunofluorescence staining. With the exception of glucose transporter GLUT1 that showed highest expression levels in colon, all investigated hexose transporters showed strongest expression in duodenum, lower levels in ileum and lowest in colon. Human newborns lack small intestinal fructose transporter GLUT5 protein expression and small intestinal atresia does not affect the expression of hexose transporters.

Enhanced Intestinal Permeability and Plasma Concentration of Metformin in Rats by the Repeated Administration of Red Ginseng Extract.

We aimed to assess the potential herb–drug interactions between Korean red ginseng extract (RGE) and metformin in rats in terms of the modulation of metformin transporters, such as organic cation transporter (Oct), multiple toxin and extrusion protein (Mate), and plasma membrane monoamine transporter (Pmat). Single treatment of RGE did not inhibit the in vitro transport activity of OCT1/2 up to 500 µg/mL and inhibited MATE1/2-K with high IC50 value (more than 147.8 µg/mL), suggesting that concomitant used of RGE did not directly inhibit OCT- and MATE-mediated metformin uptake. However, 1-week repeated administration of RGE (1.5 g/kg/day) (1WRA) to rats showed different alterations in mRNA levels of Oct1 depending on the tissue type. RGE increased intestinal Oct1 but decreased hepatic Oct1. However, neither renal Oct1/Oct2 nor Mate1/Pmat expression in duodenum, jejunum, ileum, liver, and kidney were changed in 1WRA rats. RGE repeated dose also increased the intestinal permeability of metformin; however, the permeability of 3-O-methyl-d-glucose and Lucifer yellow was not changed in 1WRA rats, suggesting that the increased permeability of metformin by multiple doses of RGE is substrate-specific. On pharmacokinetic analysis, plasma metformin concentrations following intravenous injection were not changed in 1WRA, consistent with no significant change in renal Oct1, Oct2, and mate1. Repeated doses of RGE for 1 week significantly increased the plasma concentration of metformin, with increased half-life and urinary excretion of metformin following oral administration of metformin (50 mg/kg), which could be attributed to the increased absorption of metformin. In conclusion, repeated administration of RGE showed in vivo pharmacokinetic herb–drug interaction with metformin, with regard to its plasma exposure and increased absorption in rats. These results were consistent with increased intestinal Oct1 and its functional consequence, therefore, the combined therapeutic efficacy needs further evaluation before the combination and repeated administration of RGE and metformin, an Oct1 substrate drug.

Dietary phytase supplementation during peak egg laying cycle of White Leghorn hens on nutrient utilization and functional gene mRNA expression in duodenum and kidney

ABSTRACTSeventy-five White Leghorn hens during peak egg laying cycle were randomly divided into 5 groups: 1 group with 0.32% NPP (control), 2 groups with 0.24% NPP and laboratory (T1) or commercial (T2) phytase (250 FTU/kg feed), and 2 groups with 0.16% NPP and laboratory produced (T3) or commercial (T4) phytase (500 FTU/kg feed) from 23 to 40 weeks of age. The results indicated T2 group had the lowest (P > 0.05) bone ash, followed by similar ash content in T1, T3 and control groups. Mineral concentration (Ca, P, zinc and manganese) in the bone was not affected (P > 0.05) by variation in dietary phytase and NPP level. In duodenum, NaPiIIb was up-regulated (P < 0.05) in T2 and T3, whereas Calbindin 1 (CALB1) was up-regulated (P < 0.05) only in T3. In kidney, expression of NaPiIIa and CALB1 were down-regulated (P < 0.05) in all groups. The data demonstrated that 250 FTU/kg laboratory phytase supplementation in feed was enough for replacing 50% of inorganic P and 500 FTU/kg commercial phytase capable of replacing 100% of inorganic P. The up-and down-regulation of NaPiIIb, NaPiIIa and CALB1 genes in treatment groups was independent of phytase source and NPP level in feed.

Helicobacter pylori cagA+ Is Associated with Milder Duodenal Histological Changes in Chilean Celiac Patients.

HIGHLIGHTS What is already known about this subject?Celiac disease (CD) has a high clinical and histological diversity and the mechanisms underlying this phenomenon remain elusive.H. pylori is a bacterium that chronically infect gastric and duodenal mucosa activating both a Th1/Th17 and T-reg pathways.The role of H. pylori (and the effect of their virulence factors) in CD have not yet completely elucidated.What are the new findings?cagA+ H. pylori strains are associated to milder histological damage in infected CD patients.In active-CD patients the presence of cagA+ H. pylori is associated to an increase in T-reg markers, contrasting with a downregulation in cagA+ infected potential-CD individuals.How might it impact on clinical practice in the foreseeable future?The identification of microbiological factors that could modulate inflammation and clinical expression of CD may be used in the future as preventive strategies or as supplementary treatment in patients that cannot achieve complete remission, contributing to the better care of these patients.Background: Mechanisms underlying the high clinical and histological diversity of celiac disease (CD) remain elusive. Helicobacter pylori (Hp) chronically infects gastric and duodenal mucosa and has been associated with protection against some immune-mediated conditions, but its role (specifically of cagA+ strains) in CD is unclear.Objective: To assess the relationship between gastric Hp infection (cagA+ strains) and duodenal histological damage in patients with CD.Design: Case-control study including patients with active-CD, potential-CD and non-celiac individuals. Clinical presentation, HLA genotype, Hp/cagA gene detection in gastric mucosa, duodenal histology, Foxp3 positive cells and TGF-β expression in duodenal lamina propria were analyzed.Results: We recruited 116 patients, 29 active-CD, 37 potential-CD, and 50 non-CD controls. Hp detection was similar in the three groups (~30–40%), but cagA+ strains were more common in infected potential-CD than in active-CD (10/11 vs. 4/10; p = 0.020) and non-CD (10/20; p = 0.025). Among active-CD patients, Foxp3 positivity was significantly higher in subjects with cagA+ Hp+ compared to cagA- Hp+ (p < 0.01) and Hp- (p < 0.01). In cagA+ Hp+ individuals, Foxp3 positivity was also higher comparing active- to potential-CD (p < 0.01). TGF-β expression in duodenum was similar in active-CD with cagA+ Hp+ compared to Hp- and was significantly downregulated in cagA+ potential-CD subjects compared to other groups.Conclusion: Hp infection rates were similar among individuals with/without CD, but infection with cagA+ strains was associated with milder histological damage in celiac patients infected by Hp, and in active-CD cases with higher expression of T-reg markers. Results suggest that infection by cagA+ Hp may be protective for CD progression, or conversely, that these strains are prone to colonize intestinal mucosa with less severe damage.

Xanthophylls increased HDLC level and nuclear factor PPARγ, RXRγ and RARα expression in hens and chicks.

This study was designed to investigate effects of xanthophylls on serum lipid profile (triglyceride, TG; cholesterol, CHO; high-density lipoprotein cholesterol, HDLC; and low-density lipoprotein cholesterol, LDLC) and nuclear factor (peroxisome proliferator-activated receptor gamma, PPARγ; PPAR gamma coactivator 1 alpha, PGC1α; retinoid X receptor gamma, RXRγ; and retinoic acid receptor alpha, RARα) gene expression of breeding hens and chicks. In experiment 1, 432 hens were divided into three groups and fed diets supplemented with 0 (as control group), 20 or 40mg/kg xanthophylls. Blood was sampled at 7, 14, 21, 28 and 35 days of trial. Liver, duodenum, jejunum and ileum were sampled at 35 days of trial. Results showed that serum HDLC level of hens was increased after dietary 40mg/kg xanthophyll addition for 21, 28 and 35 days, while serum TG, CHO and LDLC were not affected. Xanthophyll addition also increased PPARγ expression in jejunum, RXRγ expression in duodenum and jejunum, and RARα expression in liver and duodenum. Experiment 2 was a 2×2 factorial design. Male chicks hatched from 0 or 40mg/kg xanthophyll diet of hens were fed diet containing either 0 or 40mg/kg xanthophylls. Liver, duodenum, jejunum and ileum were sampled at 0, 7, 14 and 21 days after hatching. Blood samples were also collected at 21 days. Results showed that in ovo xanthophylls elevated PPARγ in duodenum and jejunum, and RXRγ and RARα in liver of chicks mainly within 1week after hatching, while dietary xanthophylls increased serum HDLC level and PPARγ and RXRγ in liver from 2weeks onwards. In conclusion, our research suggested xanthophylls can regulate serum lipid profile and nuclear factor expression in hens and chicks.

A comparison of two sources of methionine supplemented at different levels on heat shock protein 70 expression and oxidative stress product of Peking ducks subjected to heat stress.

The aim of this study was to examine the effects of different sources and levels of methionine (Met) on Heat shock proteins HSP70 expression and protein carbonylation in liver, HSP70 expression and malondialdehyde (MDA) concentration in intestine under heat stress conditions during summer. A total of 720 (4days old) Peking ducks were placed 20 per pen into six replicates for each of the six treatments with a 2×3 factorial arrangement, such that two sources of Met (DL-methionine [DLM] and DL-2-hydroxy-4-methylthiobutyrate [HMTBA] were supplemented at three different levels (0.05%, 0.20%, or 0.35% on as-fed basis respectively). The experiment was divided into a starter (day 4-16) and a grower (day 17-35) period. Diet supplemented with 0.35% Met significantly up-regulated the HSP70 mRNA expression in duodenum, jejunum and ileum on day 16 and 35 as well as in liver on day 35 (p<.05) of ducks. HMTBA-supplemented diets increased the HSP70 mRNA expression in duodenum, jejunum, ileum and liver on day 35 (p<.01). An increased MDA concentration was detected in jejunum of birds in 0.35% DLM-supplemented treatment on day 16 (p<.05). And decreased protein carbonylation concentration was found in DLM-supplemented treatment on day 16 (p<.01). The birds fed with 0.35% Met supplemental diet displayed lower hepatic protein carbonylation on day 16 (p<.05). In conclusion, supplementation of 0.35% Met in the duck diet showed up-regulated HSP70 expression in small intestine and liver, which may provide new perspective to the mechanism of Met function. At the same time, DLM supplemented in diet may ameliorate oxidative status of liver, while HMTBA supplementation may partially improve the intestinal oxidative status of Peking ducks.

Intestinal microbiota could transfer host Gut characteristics from pigs to mice.

BackgroundThe present study was conducted to compare the differences in gut microbiota composition and gut-phenotypes among pig breeds, and determine whether these differences would transmit to mice colonized with fecal microbiota of different pig breeds. A total of 24 1-day-old germ-free BALB/C mice were divided into 3 groups (TFM, YFM and RFM), which were transplanted with intact fecal microbiota of Tibetan pig (TP), Yorkshire pig (YP) and Rongchang pig (RP), respectively.ResultsResults showed that different pig breeds exhibited distinct gut microbiota profile based on high-throughput pyrosequencing. YP exhibited a lower Firmicutes/Bacteroidetes ratio and apparent genera differences compared with RP and TP, and higher levels of bacteria from Spirochaetes were observed in TP compared with RP and YP (P < 0.05). Transplanted porcine microbiota into GF mice replicated the phenotypes of pig donors. Moreover, the three groups of donor pigs and their mice recipients exhibited different intestinal index and morphology. TP and RP had higher intestinal weight and relative CDX2 mRNA expression in ileum than YP, and longer intestine, higher villus height of duodenum and jejunum were observed in TP compared with YP and RP (P < 0.05). TP exhibited higher GLP-2 mRNA expression in duodenum and jejunum than RP (P < 0.05). Similarly, YFM had lower intestine weight and CDX2 mRNA expression in ileum than TFM and RFM (P < 0.05). The intestine length in TFM was longer than that in RFM, and TFM had higher villus height in duodenum and jejunum and GLP-2 mRNA expression in ileum than the other two groups (P < 0.05). Besides, the digestive and absorptive ability was different among the three groups in donor pigs and mice recipients. YP had higher jejunal lactase and maltase activities than TP and RP, while TP had higher activities of jejunal ATPase, γ-GT, and relative SGLT1 mRNA expression in duodenum and jejunum than YP and RP (P < 0.05). Likewise, YFM had higher jejunal sucrase and maltase activities than TFM and RFM, whereas higher jejunal γ-GT activity and relative SGLT1 mRNA expression in duodenum and ileum were observed in TFM compared with YFM and RFM (P < 0.05). In addition, Tibetan pigs-derived microbiota improved gut barrier in mice recipients. The concentration of MDA in YP was higher than that in TP and RP (P = 0.078), and the relative ZO-1 mRNA expression in ileum in TP was higher than that in YP (P < 0.05). Likely, compared with TFM and RFM, YFM exhibited increasing MDA concentration in jejunum (P = 0.098), and the relative ZO-1 mRNA expression in duodenum and ileum in TFM were higher than that in YFM (P < 0.05).ConclusionsThere were huge differences in gut microbiota composition and gut characteristics among pig breeds, and gut microbiota could partially convey host gut characteristics from pigs to mice.Electronic supplementary materialThe online version of this article (doi:10.1186/s12866-016-0851-z) contains supplementary material, which is available to authorized users.