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1.
Nutrients ; 13(10)2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34684302

RESUMO

As part of a whole egg, egg white proteins are embedded in a lipid matrix that could modify their presentation to the immune system and their allergenic properties. The present study examines the impact of the main egg lipid components, triacylglycerides and phospholipids, in the early events of sensitization to egg. To this end, BALB/c mice were exposed intragastrically to egg lipids and egg lipid fractions, alone and in mixtures with egg white proteins, and Th2-promoting and proinflammatory effects were investigated. Our results highlight that the egg lipid fraction is responsible for Th2 adjuvant effects and point at a different influence of triacylglycerides and phospholipids on the bioavailability and immunomodulating properties of egg white proteins. While triacylglycerides promote type 2 responses at the small intestine level, phospholipids reduce the solubility of EW proteins and induce Th2 skewing in lymphoid intestinal tissues, which may have a direct impact on the development of egg allergy.


Assuntos
Proteínas do Ovo/farmacologia , Gema de Ovo/química , Imunização , Fosfolipídeos/farmacologia , Triglicerídeos/farmacologia , Animais , Galinhas , Duodeno/efeitos dos fármacos , Duodeno/metabolismo , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Intestino Delgado/metabolismo , Linfócitos/efeitos dos fármacos , Linfócitos/metabolismo , Camundongos Endogâmicos BALB C , Solubilidade , Linfócitos T/efeitos dos fármacos , Linfócitos T/metabolismo
2.
Nutrients ; 13(10)2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34684398

RESUMO

Zinc (Zn) deficiency is estimated to affect over one billion (17%) of the world's population. Zn plays a key role in various cellular processes such as differentiation, apoptosis, and proliferation, and is used for vital biochemical and structural processes in the body. Widely used biomarkers of Zn status include plasma, whole blood, and urine Zn, which decrease in severe Zn deficiency; however, accurate assessment of Zn status, especially in mild to moderate deficiency, is difficult, as studies with these biomarkers are often contradictory and inconsistent. Thus, sensitive and specific biological markers of Zn physiological status are still needed. In this communication, we provide the Zn status index (ZSI) concept, which consists of a three-pillar formula: (1) the LA:DGLA ratio, (2) mRNA gene expression of Zn-related proteins, and (3) gut microbiome profiling to provide a clear assessment of Zn physiological status and degree of Zn deficiency with respect to assessing dietary Zn manipulation. Analysis of five selected studies found that with lower dietary Zn intake, erythrocyte LA:DGLA ratio increased, mRNA gene expression of Zn-related proteins in duodenal and liver tissues was altered, and gut microbiota populations differed, where the ZSI, a statistical model trained on data from these studies, was built to give an accurate estimation of Zn physiological status. However, the ZSI needs to be tested and refined further to determine its full potential.


Assuntos
Dieta , Zinco/metabolismo , Ácido 8,11,14-Eicosatrienoico/sangue , Animais , Biomarcadores/sangue , Proteínas de Transporte de Cátions/genética , Proteínas de Transporte de Cátions/metabolismo , Galinhas , Duodeno/metabolismo , Eritrócitos/química , Alimentos Fortificados , Microbioma Gastrointestinal , Regulação da Expressão Gênica , Ácido Linoleico/sangue , Fígado/metabolismo , Modelos Animais , Zinco/administração & dosagem , Zinco/sangue , Zinco/deficiência
3.
Int J Mol Sci ; 22(18)2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34576090

RESUMO

Iron deficiency is the most common mammalian nutritional disorder. However, among mammalian species iron deficiency anemia (IDA), occurs regularly only in pigs. To cure IDA, piglets are routinely injected with high amounts of iron dextran (FeDex), which can lead to perturbations in iron homeostasis. Here, we evaluate the therapeutic efficacy of non-invasive supplementation with Sucrosomial iron (SI), a highly bioavailable iron supplement preventing IDA in humans and mice and various iron oxide nanoparticles (IONPs). Analysis of red blood cell indices and plasma iron parameters shows that not all iron preparations used in the study efficiently counteracted IDA comparable to FeDex-based supplementation. We found no signs of iron toxicity of any tested iron compounds, as evaluated based on the measurement of several toxicological markers that could indicate the occurrence of oxidative stress or inflammation. Neither SI nor IONPs increased hepcidin expression with alterations in ferroportin (FPN) protein level. Finally, the analysis of the piglet gut microbiota indicates the individual pattern of bacterial diversity across taxonomic levels, independent of the type of supplementation. In light of our results, SI but not IONPs used in the experiment emerges as a promising nutritional iron supplement, with a high potential to correct IDA in piglets.


Assuntos
Anemia Ferropriva/tratamento farmacológico , Suplementos Nutricionais , Compostos Férricos/administração & dosagem , Compostos Férricos/uso terapêutico , Nanopartículas Magnéticas de Óxido de Ferro/administração & dosagem , Nanopartículas Magnéticas de Óxido de Ferro/química , Administração Oral , Anemia Ferropriva/sangue , Animais , Animais Recém-Nascidos , Biomarcadores/metabolismo , Duodeno/metabolismo , Compostos Férricos/farmacologia , Compostos Ferrosos/uso terapêutico , Hepcidinas/sangue , Hepcidinas/genética , Masculino , Microbiota , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Suínos
4.
Nutrients ; 13(8)2021 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-34444676

RESUMO

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.


Assuntos
Gastrectomia/efeitos adversos , Hepcidinas/sangue , Ferro/deficiência , Adulto , Proteínas de Transporte de Cátions/análise , Estudos de Coortes , Suplementos Nutricionais , Duodeno/química , Duodeno/metabolismo , Eritrócitos/química , Feminino , Humanos , Absorção Intestinal/fisiologia , Ferro/administração & dosagem , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/complicações , Obesidade/cirurgia , Estudos Prospectivos , Protoporfirinas/sangue , Receptores da Transferrina/sangue , Fatores de Transcrição/análise
5.
Am J Physiol Gastrointest Liver Physiol ; 321(4): G243-G251, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34259574

RESUMO

The gallbladder is considered an important organ in maintaining digestive and metabolic homeostasis. Given that therapeutic options for gallbladder diseases are often limited to cholecystectomy, understanding gallbladder pathophysiology is essential in developing novel therapeutic strategies. Since liver X receptor ß (LXRß), an oxysterol-activated transcription factor, is strongly expressed in gallbladder cholangiocytes, the aim was to investigate LXRß physiological function in the gallbladder. Thus, we studied the gallbladders of WT and LXRß-/- male mice using immunohistochemistry, electron microscopy, qRT-PCR, bile duct cannulation, bile and blood biochemistry, and duodenal pH measurements. LXRß-/- mice presented a large gallbladder bile volume with high duodenal mRNA levels of the vasoactive intestinal polypeptide (VIP), a strong mediator of gallbladder relaxation. LXRß-/- gallbladders showed low mRNA and protein expression of Aquaporin-1, Aquaporin-8, and cystic fibrosis transmembrane conductance regulator (CFTR). A cystic fibrosis-resembling phenotype was evident in the liver showing high serum cholestatic markers and the presence of reactive cholangiocytes. For LXRß being a transcription factor, we identified eight putative binding sites of LXR on the promoter and enhancer of the Cftr gene, suggesting Cftr as a novel LXRß regulated gene. In conclusion, LXRß was recognized as a regulator of gallbladder bile volume through multiple mechanisms involving CFTR and aquaporins.NEW & NOTEWORTHY This report reveals a novel and specific role of the nuclear receptor liver X receptor ß (LXRß) in controlling biliary tree pathophysiology. LXRß-/- mice have high gallbladder bile volume and are affected by a cholangiopathy that resembles cystic fibrosis. We found LXRß to regulate the expression of both aquaporins water channels and the cystic fibrosis transmembrane conductance regulator. This opens a new field in biliary tree pathophysiology, enlightening a possible transcription factor controlling CFTR expression.


Assuntos
Aquaporina 1/metabolismo , Aquaporinas/metabolismo , Bile/metabolismo , Regulador de Condutância Transmembrana em Fibrose Cística/metabolismo , Vesícula Biliar/metabolismo , Receptores X do Fígado/metabolismo , Animais , Aquaporina 1/genética , Aquaporinas/genética , Sítios de Ligação , Proliferação de Células , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Duodeno/metabolismo , Vesícula Biliar/ultraestrutura , Receptores X do Fígado/genética , Masculino , Camundongos Knockout , Regiões Promotoras Genéticas , Peptídeo Intestinal Vasoativo/genética , Peptídeo Intestinal Vasoativo/metabolismo
6.
Nutrients ; 13(5)2021 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-34063414

RESUMO

Intestinal iron transport requires an iron importer (Dmt1) and an iron exporter (Fpn1). The hormone hepcidin regulates iron absorption by modulating Fpn1 protein levels on the basolateral surface of duodenal enterocytes. In the genetic, iron-loading disorder hereditary hemochromatosis (HH), hepcidin production is low and Fpn1 protein expression is elevated. High Fpn1-mediated iron export depletes intracellular iron, causing a paradoxical increase in Dmt1-mediated iron import. Increased activity of both transporters causes excessive iron absorption, thus initiating body iron loading. Logically then, silencing of intestinal Dmt1 or Fpn1 could be an effective therapeutic intervention in HH. It was previously established that Dmt1 knock down prevented iron-loading in weanling Hamp (encoding hepcidin) KO mice (modeling type 2B HH). Here, we tested the hypothesis that Dmt1 silencing combined with dietary iron restriction (which may be recommended for HH patients) will mitigate iron loading once already established. Accordingly, adult Hamp KO mice were switched to a low-iron (LFe) diet and (non-toxic) folic acid-coupled, ginger nanoparticle-derived lipid vectors (FA-GDLVs) were used to deliver negative-control (NC) or Dmt1 siRNA by oral, intragastric gavage daily for 21 days. The LFe diet reduced body iron burden, and experimental interventions potentiated iron losses. For example, Dmt1 siRNA treatment suppressed duodenal Dmt1 mRNA expression (by ~50%) and reduced serum and liver non-heme iron levels (by ~60% and >85%, respectively). Interestingly, some iron-related parameters were repressed similarly by FA-GDLVs carrying either siRNA, including 59Fe (as FeCl3) absorption (~20% lower), pancreatic non-heme iron (reduced by ~65%), and serum ferritin (decreased 40-50%). Ginger may thus contain bioactive lipids that also influence iron homeostasis. In conclusion, the combinatorial approach of FA-GDLV and Dmt1 siRNA treatment, with dietary iron restriction, mitigated pre-existing iron overload in a murine model of HH.


Assuntos
Administração Oral , Gengibre/química , Hepcidinas/genética , Hepcidinas/metabolismo , Sobrecarga de Ferro/metabolismo , Ferro na Dieta/metabolismo , Nanopartículas/química , Fatores de Transcrição/metabolismo , Animais , Duodeno/metabolismo , Enterócitos/metabolismo , Ácido Fólico , Expressão Gênica , Hemocromatose/genética , Homeostase , Ferro/metabolismo , Sobrecarga de Ferro/genética , Lipídeos , Fígado/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/metabolismo , Fatores de Transcrição/genética
7.
Nutrients ; 13(5)2021 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-34064724

RESUMO

Macronutrients in the gastrointestinal (GI) lumen are able to activate "intestinal brakes", feedback mechanisms on proximal GI motility and secretion including appetite and energy intake. In this review, we provide a detailed overview of the current evidence with respect to four questions: (1) are regional differences (duodenum, jejunum, ileum) present in the intestinal luminal nutrient modulation of appetite and energy intake? (2) is this "intestinal brake" effect macronutrient specific? (3) is this "intestinal brake" effect maintained during repetitive activation? (4) can the "intestinal brake" effect be activated via non-caloric tastants? Recent evidence indicates that: (1) regional differences exist in the intestinal modulation of appetite and energy intake with a proximal to distal gradient for inhibition of energy intake: ileum and jejunum > duodenum at low but not at high caloric infusion rates. (2) the "intestinal brake" effect on appetite and energy appears not to be macronutrient specific. At equi-caloric amounts, the inhibition on energy intake and appetite is in the same range for fat, protein and carbohydrate. (3) data on repetitive ileal brake activation are scarce because of the need for prolonged intestinal intubation. During repetitive activation of the ileal brake for up to 4 days, no adaptation was observed but overall the inhibitory effect on energy intake was small. (4) the concept of influencing energy intake by intra-intestinal delivery of non-caloric tastants is intriguing. Among tastants, the bitter compounds appear to be more effective in influencing energy intake. Energy intake decreases modestly after post-oral delivery of bitter tastants or a combination of tastants (bitter, sweet and umami). Intestinal brake activation provides an interesting concept for preventive and therapeutic approaches in weight management strategies.


Assuntos
Apetite , Ingestão de Energia/fisiologia , Trato Gastrointestinal/metabolismo , Bases de Dados Factuais , Carboidratos da Dieta , Gorduras na Dieta , Proteínas na Dieta , Duodeno/metabolismo , Motilidade Gastrointestinal , Humanos , Íleo/metabolismo , Jejuno/metabolismo
8.
Food Funct ; 12(14): 6157-6166, 2021 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-34079965

RESUMO

The intra-amniotic administration approach has been used to evaluate the effects of plant origin prebiotics on intestinal health and on brush border membrane functionality and morphology. Prebiotics are fermentable dietary fibers, which can positively affect the host by selectively stimulating the growth and activity of colon bacteria, thus improving intestinal health. The consumption of prebiotics increases digestive tract motility, which leads to hyperplasia and/or hypertrophy of intestinal cells, increasing nutrient digestive and absorptive surface area. This review collates information about the effects and relationship between prebiotic consumption on small intestinal brush border membrane functionality and morphology by utilizing the intra-amniotic administration approach. To date, research has shown that the intra-amniotic administration of prebiotics affects the expression of key brush border membrane functional proteins, intestinal surface area (villi height/width), and goblet cell number/size. These effects may improve brush border membrane functionality and digestive/absorptive capabilities.


Assuntos
Galinhas , Mucosa Intestinal/efeitos dos fármacos , Microvilosidades/efeitos dos fármacos , Extratos Vegetais/farmacologia , Prebióticos/administração & dosagem , Animais , Colo/microbiologia , Fibras na Dieta/administração & dosagem , Digestão , Duodeno/metabolismo , Duodeno/microbiologia , Microbioma Gastrointestinal/efeitos dos fármacos , Motilidade Gastrointestinal , Trato Gastrointestinal/metabolismo , Trato Gastrointestinal/microbiologia , Absorção Intestinal , Mucosa Intestinal/metabolismo , Intestinos/microbiologia , Microvilosidades/metabolismo
9.
PLoS One ; 16(6): e0252930, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34115808

RESUMO

BACKGROUND: Irritable bowel syndrome (IBS) is a pathologic condition characterized by changes in gut microbiome composition, low-grade inflammation, and disruption of intestinal wall permeability. The interaction between the gut microbiome and the disease manifestation remains unclear. The changing of tight junction proteins and cytokines expression throughout the gastrointestinal tract in IBS patients has not been studied yet. AIM OF THE STUDY: To assess the changes of gut microbiome composition, tight junction proteins, and cytokines expression of intestinal mucosa from the duodenum to the distal part of the colon in IBS patients and healthy volunteers. METHODS: In 31 IBS patients (16 patients with IBS-D; 15 patients with IBS-C) and 10 healthy volunteers the expression of CLD-2, CLD-3, CLD-5, IL-2, IL-10, and TNF-α in mucosal biopsy specimens was determined by morphological and immune-histochemical methods. The qualitative and quantitative composition of the intestinal microbiota was assessed based on 16S rRNA gene sequencing in both groups of patients. RESULTS: The expression of IL-2 and TNF-α was significantly increased in IBS patients compared with the controls (p<0.001), with a gradual increase from the duodenum to the sigmoid colon. The expression of IL-10, CLD-3, and CLD-5 in mucosal biopsy specimens of these patients was lower than in the control group (p<0.001). Increased ratios of Bacteroidetes and decreased ratios of Firmicutes were noted in IBS patients compared to healthy volunteers (p<0.05). CONCLUSION: IBS patients have impaired gut permeability and persisting low-grade inflammation throughout the gastrointestinal tract. Changes in the gut microbiota may support or exacerbate these changes.


Assuntos
Citocinas/metabolismo , Microbioma Gastrointestinal , Mediadores da Inflamação/metabolismo , Síndrome do Intestino Irritável/imunologia , Síndrome do Intestino Irritável/metabolismo , Síndrome do Intestino Irritável/microbiologia , Proteínas de Junções Íntimas/metabolismo , Adulto , Bactérias/classificação , Bactérias/isolamento & purificação , Biodiversidade , Estudos de Coortes , Duodeno/imunologia , Duodeno/metabolismo , Feminino , Humanos , Mucosa Intestinal/metabolismo , Masculino
10.
Biochem Biophys Res Commun ; 566: 115-122, 2021 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-34119823

RESUMO

Human intestinal organoids are expected to be applied in pharmaceutical research. Various culture media for human intestinal organoids have been developed, but it remains unclear which media are preferable for pharmacokinetic studies. Here, we cultured human intestinal organoids with three major culture media that are already used widely around the world: the medium of Sato et al. (S-medium; reported in 2011), Fujii et al. (F-medium; 2018), and Miyoshi et al. (M-medium; 2013). The growth of human intestinal organoids cultured in S-medium was faster than that in F- or M-medium. The gene expression levels of most pharmacokinetic-related enzymes or transporters in human intestinal organoids cultured in M-medium were higher than those in S- or F-medium, and comparable to those in the adult human small intestine. The level of cytochrome P450 (CYP) 3A4 activity was also highest in human intestinal organoids cultured in M-medium. Collectively, the results underscored the importance of selection and optimization of culture medium for various applications using human intestinal organoids, including pharmacokinetic studies.


Assuntos
Meios de Cultura/metabolismo , Duodeno/citologia , Organoides/metabolismo , Técnicas de Cultura de Células/métodos , Células Cultivadas , Duodeno/metabolismo , Humanos , Organoides/citologia , Farmacocinética
11.
Toxicol Appl Pharmacol ; 422: 115561, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-33957193

RESUMO

Arsenic is a global health concern that causes toxicity through ingestion of contaminated water and food. In vitro studies suggest that arsenic reduces stem and progenitor cell differentiation. Thus, this study determined if arsenic disrupted intestinal stem cell (ISC) differentiation, thereby altering the number, location, and/or function of intestinal epithelial cells. Adult male C57BL/6 mice were exposed to 0 or 100 ppb sodium arsenite (AsIII) through drinking water for 5 weeks. Duodenal sections were collected to assess changes in morphology, proliferation, and cell types. qPCR analysis revealed a 40% reduction in Lgr5 transcripts, an ISC marker, in the arsenic-exposed mice, although there were no changes in the protein expression of Olfm4. Secretory cell-specific transcript markers of Paneth (Defa1), Goblet (Tff3), and secretory transit amplifying (Math1) cells were reduced by 51%, 44%, and 30% respectively, in the arsenic-exposed mice, indicating significant impacts on the Wnt-dependent differentiation pathway. Further, protein levels of phosphorylated ß-catenin were reduced in the arsenic-exposed mice, which increased the expression of Wnt-dependent transcripts CD44 and c-myc. PCA analysis, followed by MANOVA and regression analyses, revealed significant changes and correlations between Lgr5 and the transit amplifying (TA) cell markers Math1 and Hes1, which are in the secretory cell pathway. Similar comparisons between Math1 and Defa1 show that terminal differentiation into Paneth cells is also reduced in the arsenic-exposed mice. The data suggests that ISCs are not lost following arsenic exposure, but rather, specific Wnt-dependent progenitor cell formation and terminal differentiation in the small intestine is reduced.


Assuntos
Arsenitos/toxicidade , Diferenciação Celular/efeitos dos fármacos , Duodeno/efeitos dos fármacos , Celulas de Paneth/efeitos dos fármacos , Receptores Acoplados a Proteínas G/metabolismo , Compostos de Sódio/toxicidade , Células-Tronco/efeitos dos fármacos , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Regulação para Baixo , Duodeno/metabolismo , Duodeno/patologia , Masculino , Camundongos Endogâmicos C57BL , Celulas de Paneth/metabolismo , Celulas de Paneth/patologia , Receptores Acoplados a Proteínas G/genética , Células-Tronco/metabolismo , Células-Tronco/patologia , Fator Trefoil-3/genética , Fator Trefoil-3/metabolismo , Via de Sinalização Wnt , alfa-Defensinas/genética , alfa-Defensinas/metabolismo
13.
Food Funct ; 12(13): 5837-5849, 2021 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-34018533

RESUMO

The present study was conducted to investigate the effects of dietary supplementation with Bacillus subtilis (BS) and xylo-oligosaccharides (XOS) on growth performance, intestinal morphology, intestinal microbial community, and metabolites of weaned piglets. One hundred and twenty-eight piglets were randomly allocated to one of four groups, including a control group (basal diet), BS group (basal diet + 500 g t-1 BS), XOS group (basal diet + 250 g t-1 XOS), and BS + XOS group (basal diet + 500 g t-1 BS + 250 g t-1 XOS). Dietary BS and XOS were mixed with the basal diet. All groups had eight replicates with four piglets per replicate. The experiment lasted for 42 days. The results showed that dietary XOS supplementation increased the ADFI and ADG, while decreasing the F/G. Dietary BS or XOS supplementation improved the intestinal morphology of weaned piglets by increasing the villus height and the ratio of villus height to crypt depth in the ileum. In addition, dietary XOS supplementation increased the concentrations of butyrate in the ileum and tryptamine and spermidine in the colon, while decreasing the concentration of indole in the colon compared with the control group. Dietary BS supplementation increased the colonic concentrations of butyrate, tryptamine, and cadaverine, while decreasing the concentration of skatole compared with the control group. The LEfSe analysis identified 16 biomarkers in the ileum of the BS group. The intestinal microbiota alterations of weaned piglets indicated that dietary BS or XOS supplementation could improve intestinal health by increasing the gut microbial diversity and altering the relative abundances of different bacterial species. Moreover, Spearman's correlation analysis revealed the potential link between gut microbiota alterations and metabolite changes of weaned piglets. These findings suggest that dietary XOS supplementation could alone improve the growth performance, while dietary BS or XOS and BS with XOS supplementation could influence intestinal health by altering the intestinal morphology, microbial community, and metabolites of weaned piglets. Meanwhile, there were interactions between BS and XOS in intestinal metabolites.


Assuntos
Bacillus subtilis/fisiologia , Suplementos Nutricionais , Microbioma Gastrointestinal/fisiologia , Oligossacarídeos/metabolismo , Ração Animal , Animais , Dieta , Duodeno/metabolismo , Íleo/metabolismo , Masculino , Suínos , Desmame
14.
Food Funct ; 12(13): 5913-5926, 2021 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-34028482

RESUMO

The aim of this study was to investigate the effects and potential signaling pathway of selenium-enriched Bacillus subtilis (SEBS) on beta defensin 1 (BD1) expression in chicken intestine. Chinese Huainan Partridge chickens (500 individuals) were randomly allocated into five groups, including control, inorganic Se, B. subtilis, SEBS, and a mixture of Se and B. subtilis (Se-BS). After 56 d of feeding, chicken ileal mucous membranes were harvested to detect differences in expression of BD1. The results indicated that BD1 was produced in intestinal crypt cells and secreted into the lumen through the villi brush border. BD1 was up-regulated in distal ileum segments colonized by SEBS and B. subtilis. Chicken primary intestinal crypt cells were cultured and grouped into control, inorganic Se, B. subtilis, SEBS, and Se-BS treatments to identify the receptor of B. subtilis. Results indicated that B. subtilis and SEBS were recognized by toll-like receptor 2 (TLR2), stimulating the NF-κB1 signaling pathway to increase expression of BD-1, which was further enhanced when combined with Se. Pro-inflammatory cytokines TNF-α, IL-1ß, and IL-6 were up-regulated with B. subtilis supplementation, and inhibited under the action of Se. In conclusion, B. subtilis and SEBS were recognized by the TLR2 receptor in the ileal mucous membrane, which activated the TLR2-MyD88-NF-κB1 signaling pathway to upregulate BD1 expression. In addition, Se enhanced recognition of B. subtilis and reduced levels of pro-inflammatory factors caused by estrogenic B. subtilis supplementation.


Assuntos
Bacillus subtilis/efeitos dos fármacos , Selênio/farmacologia , Transdução de Sinais/efeitos dos fármacos , Receptor 2 Toll-Like/metabolismo , beta-Defensinas/metabolismo , Animais , Galinhas , Citocinas/metabolismo , Duodeno/metabolismo , Íleo/patologia , Intestinos , NF-kappa B/metabolismo , Probióticos/farmacologia
15.
J Dairy Sci ; 104(7): 7641-7652, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33865572

RESUMO

Our objective was to evaluate effects of corn grain endosperm type and fineness of grind on feed intake, feeding behavior, and productive performance of lactating cows. Eight ruminally and duodenally cannulated Holstein cows in mid lactation (130 ± 42 d in milk; mean ± standard deviation) were used in a duplicated 4 × 4 Latin square design with 21-d periods. A 2 × 2 factorial arrangement of treatments was used with main effects of corn grain endosperm type (floury or vitreous) and fineness of grind (fine or medium). Rations included alfalfa silage, corn treatments, protein supplement, minerals, and vitamins and were formulated to contain 29% starch, 27% neutral detergent fiber, 18.2% forage neutral detergent fiber, and 18% crude protein. Corn grain treatments supplied 86.2% of dietary starch. Endosperm was 25% vitreous for the floury treatment and 66% vitreous for the vitreous treatment. The floury treatment increased rate of starch degradation by 94% (19.2 vs. 9.9%/h) and decreased rate of starch passage by 38% (16.1 vs. 25.8%/h), increasing apparent ruminal starch digestibility by 117% (53.7 vs. 24.7%). The floury treatment increased total-tract starch digestibility by 8% (92.2 vs. 85.1%) despite 37% lower postruminal starch digestion for the floury treatment compared with vitreous corn (38.4 vs. 60.7% of starch intake). Fine grind size increased apparent ruminal starch digestibility by 52% (47.2 vs. 31.1%) compared with medium grind size by increasing the rate of starch degradation by 105% (19.5 vs. 9.5%/h) with no effect on rate of starch passage. However, total-tract starch digestibility was not affected by fineness of grind because postruminal starch digestibility was 37% greater for medium compared with fine grind size (57.2 vs. 41.9% of starch intake). Endosperm type did not affect flow of nitrogen (N) fractions to the duodenum or microbial N efficiency, whereas fine grind size increased duodenal flow of nonammonia N by increasing duodenal flow of microbial N by 22% compared with medium grind size (438 vs. 359 g/d) but did not affect apparent total-tract N digestibility. No interactions were detected for any measure of starch digestion, ruminal N metabolism, or flow of N fractions to the duodenum. Endosperm type greatly affected ruminal and total-tract starch digestibility independent of the fineness of grind of corn grain with no effects on flow of N fractions.


Assuntos
Lactação , Zea mays , Animais , Bovinos , Digestão , Duodeno/metabolismo , Endosperma , Feminino , Fermentação , Cinética , Leite , Nitrogênio/metabolismo , Rúmen/metabolismo
16.
J Dairy Sci ; 104(7): 7617-7629, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33865594

RESUMO

Our objective was to evaluate the relative effects of endosperm type and conservation method of corn grain on ruminal kinetics, site of nutrient digestion, and flow of nitrogen fractions to the duodenum in lactating dairy cows. Seven ruminally and duodenally cannulated Holstein cows (73 ± 39 d in milk; mean ± SD) were used in a duplicated 4 × 4 Latin square design with 21-d periods. A 2 × 2 factorial arrangement of treatments was used, with main effects of corn grain endosperm type (floury or vitreous) and conserved as dry ground corn (DGC) or high-moisture corn (HMC). Rations were formulated to contain 27.0% starch, 26.6% neutral detergent fiber (NDF), 19.1% forage NDF, and 16.5% crude protein. Corn grain treatments supplied 86.6% of dietary starch, and alfalfa silage was the sole forage. True ruminal starch digestibility was increased by HMC compared with DGC (87.2 vs. 64.3%) and by floury compared with vitreous corn grain (83.7 vs. 67.7%). The increase for HMC compared with DGC was because of an increase in the degradation rate (33.8 vs. 23.1%/h) and a decrease in passage rate of starch (7.6 vs. 15.2%/h). The increase for floury compared with vitreous corn grain was because of an increase in the degradation rate (31.5 vs. 25.4%/h) and a decrease in rate of starch passage from the rumen (7.9 vs. 14.9%/h). Apparent total-tract starch digestibility was increased by HMC compared with DGC and by floury compared with vitreous corn, but the increase for floury corn was greater for the DGC treatment. Dry ground corn compared with HMC tended to increase nonammonia N flow to the duodenum (466 vs. 431 g/d) by increasing flow of nonammonia nonmicrobial N (211 vs. 111 g/d) despite a decrease in microbial N flow (255 vs. 320 g/d). Vitreous corn increased nonammonia nonmicrobial N flow to the duodenum (187 vs. 135 g/d) compared with floury corn, but microbial N flow to the duodenum was not affected by endosperm type. Efficiency of microbial N production was not affected by treatment. Endosperm type and conservation method of corn grain greatly affect digestion kinetics and ruminal digestibility of starch as well as flow of N fractions to the duodenum and should be considered during diet formulation for lactating cows.


Assuntos
Rúmen , Zea mays , Animais , Bovinos , Digestão , Duodeno/metabolismo , Endosperma , Feminino , Fermentação , Cinética , Lactação , Leite , Nitrogênio/metabolismo , Distribuição Aleatória , Rúmen/metabolismo
17.
Nutrients ; 13(3)2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33808622

RESUMO

This work aimed to define the microbial consortia that are able to digest gluten into non-toxic and non-immunogenic peptides in the human gastrointestinal tract. METHODS: 131 out of 504 tested Bacillus and lactic acid bacteria, specifically Bacillus (64), lactobacilli (63), Pediococcus (1), and Weissella (3), showed strong gastrointestinal resistance and were selected for their PepN, PepI, PepX, PepO, and PepP activities toward synthetic substrates. Based on multivariate analysis, 24 strains were clearly distinct from the other tested strains based on having the highest enzymatic activities. As estimated by RP-HPLC and nano-ESI-MS/MS, 6 cytoplasmic extracts out of 24 selected strains showed the ability to hydrolyze immunogenic epitopes, specifically 57-68 of α9-gliadin, 62-75 of A-gliadin, 134-153 of γ-gliadin, and 57-89 (33-mer) of α2-gliadin. Live and lysed cells of selected strains were combined into different microbial consortia for hydrolyzing gluten under gastrointestinal conditions. Commercial proteolytic enzymes (Aspergillusoryzae E1, Aspergillusniger E2, Bacillussubtilis Veron HPP, and Veron PS proteases) were also added to each microbial consortium. Consortium activity was evaluated by ELISA tests, RP-HPLC-nano-ESI-MS/MS, and duodenal explants from celiac disease patients. RESULTS: two microbial consortia (Consortium 4: Lactiplantibacillus (Lp.) plantarum DSM33363 and DSM33364, Lacticaseibacillus (Lc.) paracasei DSM33373, Bacillussubtilis DSM33298, and Bacilluspumilus DSM33301; and Consortium 16: Lp. plantarum DSM33363 and DSM33364, Lc. paracasei DSM33373, Limosilactobacillusreuteri DSM33374, Bacillusmegaterium DSM33300, B.pumilus DSM33297 and DSM33355), containing commercial enzymes, were able to hydrolyze gluten to non-toxic and non-immunogenic peptides under gastrointestinal conditions. CONCLUSIONS: the results of this study provide evidence that selected microbial consortia could potentially improve the digestion of gluten in gluten-sensitive patients by hydrolyzing the immunogenic peptides during gastrointestinal digestion.


Assuntos
Bactérias/metabolismo , Digestão , Microbioma Gastrointestinal/fisiologia , Trato Gastrointestinal/metabolismo , Glutens/metabolismo , Bacillus , Bactérias/classificação , Duodeno/metabolismo , Epitopos , Trato Gastrointestinal/microbiologia , Glutens/imunologia , Humanos , Hidrólise , Consórcios Microbianos , Peptídeo Hidrolases/metabolismo , Peptídeos
18.
PLoS One ; 16(4): e0249179, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33844694

RESUMO

There is no FDA approved therapy for the treatment of celiac disease (CeD), aside from avoidance of dietary gluten. Larazotide acetate (LA) is a first in class oral peptide developed as a tight junction regulator, which is a lead candidate for management of CeD. A delayed release formulation was tested in vitro and predicted release in the mid duodenum and jejunum, the target site of CeD. The aim of this study was to follow the concentration versus time profile of orally administered LA in the small intestine using a porcine model. A sensitive liquid chromatography/tandem mass spectrometry method was developed to quantify LA concentrations in porcine intestinal fluid samples. Oral dosing of LA (1 mg total) in overnight fasted pigs resulted in time dependent appearance of LA in the distal duodenum and proximal jejunum. Peak LA concentrations (0.32-1.76 µM) occurred at 1 hour in the duodenum and in proximal jejunum following oral dosing, with the continued presence of LA (0.02-0.47 µM) in the distal duodenum and in proximal jejunum (0.00-0.43 µM) from 2 to 4 hours following oral dosing. The data shows that LA is available in detectable concentrations at the site of CeD.


Assuntos
Doença Celíaca/tratamento farmacológico , Oligopeptídeos/farmacocinética , Administração Oral , Animais , Liberação Controlada de Fármacos , Duodeno/metabolismo , Jejuno/metabolismo , Oligopeptídeos/administração & dosagem , Oligopeptídeos/uso terapêutico , Suínos
19.
Mol Pharm ; 18(5): 1895-1904, 2021 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-33886332

RESUMO

Intestinal efflux transporters affect the gastrointestinal processing of many drugs but further data on their intestinal expression levels are required. Relative mRNA expression and relative and absolute protein expression data of transporters are commonly measured by real-time polymerase chain reaction (RT-PCR), Western blot and mass spectrometry-based targeted proteomics techniques. All of these methods, however, have their own strengths and limitations, and therefore, validation for optimized quantification methods is needed. As such, the identification of the most appropriate technique is necessary to effectively translate preclinical findings to first-in-human trials. In this study, the mRNA expression and protein levels of the efflux transporter P-glycoprotein (P-gp) in jejunal and ileal epithelia of 30 male and female human subjects, and the duodenal, jejunal, ileal and colonic tissues in 48 Wistar rats were quantified using RT-PCR, Western blot and liquid chromatography-tandem mass spectrometry (LC-MS/MS). A similar sex difference was observed in the expression of small intestinal P-gp in humans and Wistar rats where P-gp was higher in males than females with an increasing trend from the proximal to the distal parts in both species. A strong positive linear correlation was determined between the Western blot data and LC-MS/MS data in the small intestine of humans (R2 = 0.85). Conflicting results, however, were shown in rat small intestinal and colonic P-gp expression between the techniques (R2 = 0.29 and 0.05, respectively). In RT-PCR and Western blot, an internal reference protein is experimentally required; here, beta-actin was used which is innately variable along the intestinal tract. Quantification via LC-MS/MS can provide data on P-gp expression without the need for an internal reference protein and consequently, can give higher confidence on the expression levels of P-gp along the intestinal tract. Overall, these findings highlight similar trends between the species and suggest that the Wistar rat is an appropriate preclinical animal model to predict the oral drug absorption of P-gp substrates in the human small intestine.


Assuntos
Subfamília B de Transportador de Cassetes de Ligação de ATP/análise , Mucosa Intestinal/metabolismo , Subfamília B de Transportador de Cassetes de Ligação de ATP/metabolismo , Adulto , Idoso , Animais , Ensaios Clínicos Fase I como Assunto , Avaliação Pré-Clínica de Medicamentos/métodos , Duodeno/metabolismo , Feminino , Humanos , Íleo/metabolismo , Absorção Intestinal , Jejuno/metabolismo , Masculino , Pessoa de Meia-Idade , Ratos , Fatores Sexuais , Especificidade da Espécie , Espectrometria de Massas em Tandem
20.
Biomed Pharmacother ; 137: 111385, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33761606

RESUMO

A large body of evidence suggests that supplementation of butyric acid exerts beneficial intestinal and extra-intestinal effects. Unfortunately, unpleasant sensorial properties and unfavourable physico-chemical properties strongly limit its use in food supplements and foods for medicinal purposes. N-(1-carbamoyl-2-phenyl-ethyl) butyramide (FBA) is a new butyric acid releaser in solid form with neutral sensorial properties. The aim of this investigation is to provide preliminary information on its pharmacokinetic and toxicological properties through the study of a) in vivo bioavailability of FBA administered by oral gavage to male and female Swiss CD1 mice in comparison with sodium butyrate, b) the influence of digestion on FBA stability through an in vitro simulated oro-gastro-duodenal digestion process, and c) in vitro toxicological profile by means of the Ames Test and Micronucleus Test. The results reveal that FBA is a good butyric acid releaser, being able to increase butyrate serum concentration in a dose and time dependent manner in both male and female mice with a pharmacokinetic profile similar to that obtained from sodium butyrate as such. These data are confirmed by investigating the influence of digestion on FBA, which undergoes extensive hydrolysis following oro-gastro-duodenal digestion, especially in duodenal conditions, with a residual concentration of less than 10% of the initial FBA concentration. Finally, in the Ames and Micronucleus Tests, FBA does not show any in vitro genotoxicity as it is non mutagenic in the Ames Test and results to be unable to induce chromosome breaks in the Micronucleus Test. In conclusion, FBA is a new butyric acid releaser that can overcome the disadvantages of butyric acid while maintaining the same pharmacokinetic properties and safety profile, as shown by the results of the preliminary in vitro toxicological studies performed in this investigation.


Assuntos
Butiratos/farmacologia , Ácido Butírico/metabolismo , Animais , Disponibilidade Biológica , Ácido Butírico/sangue , Quebra Cromossômica/efeitos dos fármacos , Suplementos Nutricionais , Digestão , Relação Dose-Resposta a Droga , Duodeno/metabolismo , Feminino , Mucosa Gástrica/metabolismo , Masculino , Camundongos , Testes para Micronúcleos , Testes de Mutagenicidade
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