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1.
Nutrients ; 13(8)2021 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-34444916

RESUMO

The study was conducted to explore actions of decanoic acid on regulating intestinal barrier and antioxidant functions in intestinal epithelium cells isolated from porcine jejunum (IPEC-J2) and C57/BL6 mice models. In vitro and vivo assays, mice and IPEC-J2 cells treated by H2O2 were disposed of sodium decanoate and sodium butyrate to determine intestinal barrier and antioxidant functions of the host. Results showed that sodium decanoate upregulated expression of tight junction proteins and improved antioxidant capacity in both IPEC-J2 cells treated by H2O2 and mice models (p < 0.05). Sodium decanoate increased weight gain and ileal villus height of mice compared with control and sodium butyrate treatments (p < 0.05). Sodium decanoate increased α-diversity of ileal microbiota, volatile fatty acids concentration, and G protein-coupled receptor-43 (GPR-43) expression in the ileum and colon of mice (p < 0.05). In conclusion, sodium decanoate improved antioxidant capacity, intestinal morphology, and gut physical barrier of intestinal epithelial cells, resulting in an increase growth performance of mice, which is mediated through activating GPR-43 signaling.


Assuntos
Antioxidantes/metabolismo , Ácidos Decanoicos/metabolismo , Mucosa Intestinal/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Animais , Ácido Butírico/metabolismo , Colo/metabolismo , Células Epiteliais/metabolismo , Microbioma Gastrointestinal , Íleo/metabolismo , Jejuno/metabolismo , Camundongos , Modelos Animais , Transdução de Sinais , Suínos , Junções Íntimas/metabolismo , Regulação para Cima
2.
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
3.
Poult Sci ; 100(7): 101195, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34107437

RESUMO

Two experiments were conducted to determine energy (Exp. 1) and P (Exp. 2) utilization in poultry meal (PM) for broiler chickens. A total of 192 birds were allotted to 3 experimental diets in a randomized complete block design with BW as a blocking factor on d 15 and 16 post hatching in Exp. 1 and 2, respectively. Each diet was fed to 8 replicate cages with 8 birds per cage in both experiments. Initial BW of birds in Exp. 1 and 2 were 438 ± 76.9 g and 543 ± 50.2 g, respectively. Three corn-soybean meal-based diets were prepared to contain 0, 80, or 160 g/kg in Exp. 1 and 0, 50, or 100 g/kg in Exp. 2. In Exp. 1, the addition of PM to the reference diet linearly decreased (P < 0.01) the apparent ileal digestibility of DM and gross energy (GE), as well as the apparent total tract utilization (ATTU) of DM, GE, and N in diets; but did not affect the ileal digestible energy, ME, and MEn of diets. The ileal digestible energy, ME, and MEn of PM estimated by the regression method were 4,002, 3,756, and 3,430 kcal/kg DM, respectively, representing 58 to 68% of the GE in PM. In Exp. 2, graded concentration of PM in the reference diet linearly decreased (P < 0.05) ATTU of DM but linearly increased (P < 0.01) ATTU of P and quadratically increased ATTU of Ca in diets. The true ileal digestibility and true total tract utilization of P in PM estimated by the regression method were 77.5 and 79.0%, respectively. In conclusion, these results showed that inclusion of poultry meal in the diets of broiler chickens reduced the digestibility of GE but increased the utilization of P. The regression-estimated energy values and P digestibility of PM in the current studies may be used in diet formulation.


Assuntos
Fenômenos Fisiológicos da Nutrição Animal , Galinhas , Ração Animal/análise , Animais , Dieta , Digestão , Metabolismo Energético , Íleo/metabolismo , Fósforo/metabolismo , Aves Domésticas , Zea mays
4.
Sci Rep ; 11(1): 13533, 2021 06 29.
Artigo em Inglês | MEDLINE | ID: mdl-34188154

RESUMO

The host receptor for SARS-CoV-2, angiotensin-converting enzyme 2 (ACE2), is highly expressed in small intestine. Our aim was to study colonic ACE2 expression in Crohn's disease (CD) and non-inflammatory bowel disease (non-IBD) controls. We hypothesized that the colonic expression levels of ACE2 impacts CD course. We examined the expression of colonic ACE2 in 67 adult CD and 14 NIBD control patients using RNA-seq and quantitative (q) RT-PCR. We validated ACE2 protein expression and localization in formalin-fixed, paraffin-embedded matched colon and ileal tissues using immunohistochemistry. The impact of increased ACE2 expression in CD for the risk of surgery was evaluated by a multivariate regression analysis and a Kaplan-Meier estimator. To provide critical support for the generality of our findings, we analyzed previously published RNA-seq data from two large independent cohorts of CD patients. Colonic ACE2 expression was significantly higher in a subset of adult CD patients which was defined as the ACE2-high CD subset. IHC in a sampling of ACE2-high CD patients confirmed high ACE2 protein expression in the colon and ileum compared to ACE2-low CD and NIBD patients. Notably, we found that ACE2-high CD patients are significantly more likely to undergo surgery within 5 years of CD diagnosis, and a Cox regression analysis found that high ACE2 levels is an independent risk factor for surgery (OR 2.17; 95% CI, 1.10-4.26; p = 0.025). Increased intestinal expression of ACE2 is associated with deteriorated clinical outcomes in CD patients. These data point to the need for molecular stratification that can impact CD disease-related outcomes.


Assuntos
Enzima de Conversão de Angiotensina 2/metabolismo , Doença de Crohn/patologia , Adolescente , Adulto , Enzima de Conversão de Angiotensina 2/genética , Doença de Crohn/metabolismo , Doença de Crohn/cirurgia , Feminino , Humanos , Íleo/metabolismo , Íleo/patologia , Imuno-Histoquímica , Doenças Inflamatórias Intestinais/metabolismo , Doenças Inflamatórias Intestinais/patologia , Masculino , Prognóstico , Modelos de Riscos Proporcionais , RNA Mensageiro/química , RNA Mensageiro/metabolismo , Fatores de Risco , Análise de Sequência de RNA , Adulto Jovem
5.
Am J Physiol Gastrointest Liver Physiol ; 321(1): G55-G66, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-33978477

RESUMO

Regulation of bile acid metabolism is normally discussed as the regulation of bile acid synthesis, which serves to compensate for intestinal loss in order to maintain a constant pool size. After a meal, bile acids start cycling in the enterohepatic circulation. Farnesoid X receptor-dependent ileal and hepatic processes lead to negative feedback inhibition of bile acid synthesis. When the intestinal bile acid flux decreases, the inhibition of synthesis is released. The degree of inhibition of synthesis and the mechanism and degree of activation are still unknown. Moreover, in humans, a biphasic diurnal expression pattern of bile acid synthesis has been documented, indicating maximal synthesis around 3 PM and 9 PM. Quantitative data on the hourly synthesis schedule as compensation for intestinal loss are lacking. In this review, we describe the classical view on bile acid metabolism and present alternative concepts that are based on the overlooked feature that bile acids transit through the enterohepatic circulation very rapidly. A daily profile of the cycling and total bile acid pool sizes and potential controlled and uncontrolled mechanisms for synthesis are predicted. It remains to be elucidated by which mechanism clock genes interact with the Farnesoid X receptor-controlled regulation of bile acid synthesis. This mechanism could become an attractive target to enhance bile acid synthesis at night, when cholesterol synthesis is high, thus lowering serum LDL-cholesterol.


Assuntos
Ácidos e Sais Biliares/metabolismo , Circulação Êntero-Hepática/fisiologia , Intestinos/fisiologia , Fígado/metabolismo , Animais , Retroalimentação Fisiológica/fisiologia , Humanos , Íleo/metabolismo
6.
Biomed Res Int ; 2021: 6648435, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33959661

RESUMO

Muscovy ducks are among the best meat ducks in the world. The objective of this study was to identify genes related to growth metabolism through transcriptome analysis of the ileal tissue of Muscovy ducks. Duck ileum samples with the highest (H group, n = 5) and lowest (L group, n = 5) body weight were selected from two hundred 70-day-old Muscovy ducks for transcriptome analysis by RNA sequencing. In the screening of differentially expressed genes (DEGs) between the H and L groups, a total of 602 DEGs with a fold change no less than 2 were identified, among which 285 were upregulated and 317 were downregulated. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that glutathione metabolism, pyrimidine metabolism, and protein digestion and absorption processes played a vital role in regulating growth and metabolism. The results showed that 7 genes related to growth and metabolism, namely, ANPEP, ENPEP, UPP1, SLC2A2, SLC6A19, NME4, and LOC106034733, were significantly expressed in group H, which was consistent with the phenotype results. The validation of these 7 genes using real-time quantitative PCR results indicated that the expression level of ENPEP was significantly different between the H and L groups (P < 0.05). This study provides a theoretical basis for exploring the influence of the ileum on growth and metabolism in ducks.


Assuntos
Patos , Perfilação da Expressão Gênica , Transcriptoma/genética , Animais , Patos/genética , Patos/crescimento & desenvolvimento , Patos/metabolismo , Perfilação da Expressão Gênica/métodos , Perfilação da Expressão Gênica/normas , Íleo/química , Íleo/metabolismo , Íleo/fisiologia , Reação em Cadeia da Polimerase em Tempo Real , Transcriptoma/fisiologia
7.
Clin Transl Gastroenterol ; 12(4): e00329, 2021 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-33843785

RESUMO

INTRODUCTION: Previous studies in patients with irritable bowel syndrome (IBS) showed immune activation, secretion, and barrier dysfunction in duodenal, jejunal, or colorectal mucosa. This study aimed to measure ileal mucosal expression of genes and proteins associated with mucosal functions. METHODS: We measured by reverse transcription polymerase chain reaction messenger RNA (mRNA) expression of 78 genes (reflecting tight junction proteins, chemokines, innate immunity, ion channels, and transmitters) and 5 proteins (barrier, bile acid receptor, and ion exchanger) in terminal ileal mucosa from 11 patients with IBS-diarrhea (IBS-D), 17 patients with IBS-constipation (IBS-C), and 14 healthy controls. Fold changes in mRNA were calculated using 2(-Δ, ΔCT) formula. Group differences were measured using analysis of variance. Protein ratios relative to healthy controls were based on Western blot analysis. Nominal P values (P < 0.05) are reported. RESULTS: In ileal mucosal biopsies, significant differences of mRNA expression in IBS-D relative to IBS-C were upregulation of barrier proteins (TJP1, FN1, CLDN1, and CLDN12), repair function (TFF1), and cellular functions. In ileal mucosal biopsies, mRNA expression in IBS-C relative to healthy controls was reduced GPBAR1 receptor, myosin light chain kinase (MYLK in barrier function), and innate immunity (TLR3), but increased mRNA expression of cadherin cell adhesion mechanisms (CTNNB1) and transport genes SLC9A1 (Na-H exchanger [NHE1]) and INADL (indirect effect on ion transport). DISCUSSION: These data support a role of ileal mucosal dysfunction in IBS, including barrier dysfunction in IBS-D and alterations in absorption/secretion mechanisms in IBS-C.


Assuntos
Íleo/metabolismo , Mucosa Intestinal/metabolismo , Síndrome do Intestino Irritável/complicações , Síndrome do Intestino Irritável/metabolismo , RNA Mensageiro/genética , Regulação para Cima , Biópsia , Caderinas/metabolismo , Adesão Celular , Quimiocinas/metabolismo , Constipação Intestinal/etiologia , Diarreia/etiologia , Feminino , Humanos , Imunidade Inata , Absorção Intestinal , Canais Iônicos/metabolismo , Síndrome do Intestino Irritável/patologia , Masculino , Pessoa de Meia-Idade , Proteínas de Junções Íntimas/metabolismo
8.
Toxins (Basel) ; 13(4)2021 04 13.
Artigo em Inglês | MEDLINE | ID: mdl-33924586

RESUMO

Plant materials used in the production of pig feed are frequently contaminated with mycotoxins. T-2 toxin is a secondary metabolite of selected Fusarium species, and it can exert a harmful influence on living organisms. Most mycotoxins enter the body via the gastrointestinal tract, and they can modulate the gut-associated lymphoid tissue (GALT) function. However, little is known about the influence of low T-2 toxin doses on GALT. Therefore, the aim of this study was to evaluate the effect of T-2 toxin administered at 50% of the lowest-observed-adverse-effect level (LOAEL) on the percentage of CD2+ T cells, CD4+ T helper cells, CD8+ cytotoxic T cells, CD4+CD8+ double-positive T cells, TCRγδ+ cells, CD5+CD8- B1 cells, and CD21+ B2 cells, and the secretion of proinflammatory (IFN-γ, IL-1ß, IL-2, IL-12/23p40, IL-17A), anti-inflammatory, and regulatory (IL-4, IL-10, TGF-ß) cytokines in the porcine ileal wall. The results of the study revealed that T-2 toxin disrupts the development of tolerance to food antigens by enhancing the secretion of proinflammatory and regulatory cytokines and decreasing the production of anti-inflammatory TGF-ß. T-2 toxin triggered the cellular response, which was manifested by an increase in the percentage of CD8+ T cells and a decrease in the percentage of B2 and Tγδ lymphocytes.


Assuntos
Subpopulações de Linfócitos B/efeitos dos fármacos , Citocinas/metabolismo , Íleo/efeitos dos fármacos , Toxina T-2/toxicidade , Subpopulações de Linfócitos T/efeitos dos fármacos , Ração Animal/microbiologia , Animais , Antígenos , Subpopulações de Linfócitos B/imunologia , Subpopulações de Linfócitos B/metabolismo , Hipersensibilidade Alimentar/imunologia , Hipersensibilidade Alimentar/metabolismo , Microbiologia de Alimentos , Íleo/imunologia , Íleo/metabolismo , Tolerância Imunológica , Masculino , Fenótipo , Via Secretória , Sus scrofa , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo
9.
Int J Biol Macromol ; 182: 595-611, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-33836198

RESUMO

This study investigated the effects of Moringa oleifera polysaccharides (MOP) on the serum indexes, small intestinal morphology, small intestinal metabolic profile, and caecal microbiota of mice. A new type of polysaccharides with 104,031 Da molecular weight and triple helix structure was isolated from M. oleifera leaves for in vivo experiment. Forty male SPF C57BL/6 mice aged 4 weeks were average divided into four groups randomly according to the MOP gavaged daily (0, 20, 40 and 60 mg/kg body weight MOP). After a 7-day preliminary trial period and a 28-day official trial period, the mice were slaughtered. Results showed that MOP reduced glucose, total cholesterol, and malondialdehyde. It also improved superoxide dismutase and catalase in serum (P < 0.05). For small intestinal morphology, MOP improved the villi length and crypt depth in both ileum and jejunum (P < 0.05); the ratio of villi length to crypt depth in jejunum increased (P < 0.05). MOP could cause the increase of beneficial bacteria and the decrease of harmful bacteria in caecum, further affecting the function of microbiota. In addition, MOP regulated 114 metabolites enriched in the pathway related to the synthesis and metabolism of micromolecules. In sum, MOP exerted positive effects on the serum indexes and intestinal health of mice.


Assuntos
Ceco/efeitos dos fármacos , Microbioma Gastrointestinal , Metaboloma , Moringa oleifera/química , Polissacarídeos/farmacologia , Animais , Glicemia/análise , Catalase/sangue , Ceco/metabolismo , Ceco/microbiologia , Colesterol/sangue , Íleo/efeitos dos fármacos , Íleo/metabolismo , Jejuno/efeitos dos fármacos , Jejuno/metabolismo , Masculino , Malondialdeído/sangue , Camundongos , Camundongos Endogâmicos C57BL , Superóxido Dismutase/sangue
10.
Nutrients ; 13(4)2021 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-33920682

RESUMO

(1) Background: Lactose digestion depends on persistence genotypes (including rs4988235), the frequency of which exhibits broad geographical variability. However, little is known about the relationship between lactase (LCT) genotypes and intestinal expression of LCT. We aimed to investigate ileal expression of LCT depending on main genetic polymorphisms (rs4988235, rs3754689, rs3739022), age, sex, smoking status, body mass index (BMI), and the expression of other genes; (2) Methods: phenotype, array-based genotype, and ileal mucosal biopsy expression data were obtained from the CEDAR study; (3) Results: analyses included 196 healthy Europeans (53.6% women) aged 53.0 ± 13.6 years with a mean BMI of 25.6 ± 4.2 kg/m2, of whom 17.4% were smoking. Ileal LCT expression was mostly independent of age, sex, BMI, or smoking. Rs4988235 homozygous minor allele (GG) associated with lower LCT expression (vs. AG p = 2.2 × 10-6, vs. AA p = 1.1 × 10-7). Homozygous major allele of rs3754689 (GG) was related to higher LCT expression (vs. AG p = 1.7 × 10-5, vs. AA p = 0.0074). Rs3754689 genotype did not modify LCT expression (GG vs. AG p = 0.051) in rs4988235-heterozygous subgroup. Interestingly, CD14, which is a marker of monocytes and macrophages, was the strongest negative transcriptomic correlate of LCT expression (r = -0.57, pFDR = 1.1 × 10-14); (4) Conclusions: both rs4988235 and rs3754689 associated with ileal LCT expression, which did not seem related to age, sex, smoking, or BMI. The inverse correlation between LCT and CD14 expression in the ileum is striking and requires further investigation.


Assuntos
Grupo com Ancestrais do Continente Europeu/genética , Íleo/metabolismo , Mucosa Intestinal/metabolismo , Lactase/genética , Polimorfismo Genético , Adulto , Fatores Etários , Idoso , Biópsia , Índice de Massa Corporal , Feminino , Genótipo , Voluntários Saudáveis , Humanos , Receptores de Lipopolissacarídeos/metabolismo , Masculino , Pessoa de Meia-Idade , Fenótipo , Fatores Sexuais
11.
Toxicol Appl Pharmacol ; 421: 115543, 2021 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-33872679

RESUMO

Nimodipine is a clinically used dihydropyridine L-type calcium channel antagonist that effectively inhibits transmembrane Ca2+ influx following the depolarization of smooth muscle cells, but the detailed effect on smooth muscle contraction is not fully understood. Ca2+-activated Cl- channels (CaCCs) in vascular smooth muscle cells (VSMCs) may regulate vascular contractility. We found that nimodipine can inhibit transmembrane protein 16A (TMEM16A) activity in a concentration-dependent manner by cell-based fluorescence-quenching assay and short-circuit current analysis, with an IC50 value of ~5 µM. Short-circuit current analysis also showed that nimodipine prevented Ca2+-activated Cl- current in both HT-29 cells and mouse colonic epithelia accompanied by significantly decreased cytoplasmic Ca2+ concentrations. In the absence of extracellular Ca2+, nimodipine still exhibited an inhibitory effect on TMEM16A/CaCCs. Additionally, the application of nimodipine to CFTR-expressing FRT cells and mouse colonic mucosa resulted in mild activation of CFTR-mediated Cl- currents. Nimodipine inhibited basolateral CCh-activated K+ channel activity with no effect on Na+/K+-ATPase activity. Evaluation of intestinal smooth muscle contraction showed that nimodipine inhibits intestinal smooth muscle contractility and frequency, with an activity pattern that was similar to that of non-specific inhibitors of CaCCs. In aortic smooth muscle, the expression of TMEM16A in thoracic aorta is higher than that in abdominal aorta, corresponding to stronger maximum contractility in thoracic aorta smooth muscle stimulated by phenylephrine (PE) and Eact. Nimodipine completely inhibited the contraction of aortic smooth muscle stimulated by Eact, and partially inhibited the contraction stimulated by PE. In summary, the results indicate that nimodipine effectively inhibits TMEM16A/CaCCs by reduction transmembrane Ca2+ influx and directly interacting with TMEM16A, explaining the mechanisms of nimodipine relaxation of intestinal and aortic smooth muscle contraction and providing new targets for pharmacological applications.


Assuntos
Anoctamina-1/antagonistas & inibidores , Bloqueadores dos Canais de Cálcio/toxicidade , Contração Muscular/efeitos dos fármacos , Músculo Liso Vascular/metabolismo , Músculo Liso/efeitos dos fármacos , Nimodipina/toxicidade , Vasoconstrição/efeitos dos fármacos , Animais , Anoctamina-1/metabolismo , Aorta Abdominal/efeitos dos fármacos , Aorta Abdominal/metabolismo , Aorta Torácica/efeitos dos fármacos , Aorta Torácica/metabolismo , Sinalização do Cálcio/efeitos dos fármacos , Células HT29 , Humanos , Íleo/efeitos dos fármacos , Íleo/metabolismo , Técnicas In Vitro , Masculino , Camundongos Endogâmicos C57BL , Músculo Liso/metabolismo , Músculo Liso Vascular/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley
12.
Nutrients ; 13(3)2021 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-33799564

RESUMO

The prebiotic effect of high ß-glucan barley (HGB) flour on the innate immune system of high-fat model mice was investigated. C57BL/6J male mice were fed a high-fat diet supplemented with HGB flour for 90 days. Secretory immunoglobulin A (sIgA) in the cecum and serum were analyzed by enzyme-linked immunosorbent assays (ELISA). Real-time PCR was used to determine mRNA expression levels of pro- and anti-inflammatory cytokines such as interleukin (IL)-10 and IL-6 in the ileum as well as the composition of the microbiota in the cecum. Concentrations of short-chain fatty acids (SCFAs) and organic acids were analyzed by GC/MS. Concentrations of sIgA in the cecum and serum were increased in the HGB group compared to the control. Gene expression levels of IL-10 and polymeric immunoglobulin receptor (pIgR) significantly increased in the HGB group. HGB intake increased the bacterial count of microbiota, such as Bifidobacterium and Lactobacillus. Concentrations of propionate and lactate in the cecum were increased in the HGB group, and a positive correlation was found between these organic acids and the IL-10 expression level. Our findings showed that HGB flour enhanced immune function such as IgA secretion and IL-10 expression, even when the immune system was deteriorated by a high-fat diet. Moreover, we found that HGB flour modulated the gut microbiota, which increased the concentration of SCFAs, thereby stimulating the immune system.


Assuntos
Ceco/imunologia , Farinha , Hordeum , Íleo/imunologia , Obesidade/imunologia , Prebióticos , beta-Glucanas/análise , Animais , Carga Bacteriana , Peso Corporal , Ácidos Carboxílicos/análise , Ceco/química , Ceco/microbiologia , Citocinas/genética , Citocinas/metabolismo , Dieta , Ingestão de Alimentos , Ácidos Graxos Voláteis/análise , Fezes/química , Microbioma Gastrointestinal , Perfilação da Expressão Gênica , Íleo/metabolismo , Imunoglobulina A Secretora/análise , Imunoglobulina A Secretora/sangue , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Tamanho do Órgão , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores de Imunoglobulina Polimérica/genética , Receptores de Imunoglobulina Polimérica/metabolismo
13.
PLoS One ; 16(3): e0247420, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33765064

RESUMO

The effect of two microbial phytases at two dose-levels on performance and apparent ileal digestibility (AID) of nutrients in broilers fed European-type diets was studied. A total of 1,200 d-old Ross 308 male broilers were randomly assigned to 5 treatments with 30 birds/pen and 8 pens/treatment. A nutritionally adequate positive control (PC) diet was tested against 4 experimental diets containing reduced total P, retainable P, Ca and Na as per the recommended nutritional contribution for Buttiauxella phytase (Phy B) at 1,000 FTU/kg (-1.87 g/kg, -1.59 g/kg, -1.99 g/kg and -0.4 g/kg vs. PC, respectively). Experimental diets were supplemented with Phy B at 500 FTU/kg or 1,000 FTU/kg, or Citrobacter phytase (Phy C) at 1,000 FTU/kg or 2,000 FTU/kg. Diets were based on corn, soybean meal, rapeseed meal and sunflower meal and formulated by phase (starter 1-10 d, grower 11-21 d) in crumbled or pelleted form. Overall (d 1-21), at 1,000 FTU/kg, birds fed Phy C exhibited lower BWG (-2.7%), FI (-3.4%) and tibia ash (-2.2%) vs. PC (P < 0.05), and reduced BWG (-3.6%), FI (-3.9%) and tibia ash (-1.8%) vs. Phy B (P < 0.05). Phy B at 1,000 FTU/kg and Phy C at 2,000 FTU/kg maintained performance equivalent to the PC. Digestibility of Ca did not differ among phytase treatments but at 1,000 FTU/kg AID P was greater with Phy B than Phy C (72.3% vs. 62.7%, P < 0.05). Ileal phytate (myo-inositol hexakisphosphate, IP6) digestibility was greatest with Phy B at 1,000 FTU/kg which was higher than Phy C at 1,000 FTU/kg (87.6 vs. 60.6%, P < 0.05). The findings indicate a higher phytate degradation rate of Phy B than Phy C at equivalent dose-level and this is correlated to the performance of the broilers.


Assuntos
6-Fitase/metabolismo , Ração Animal/análise , Digestão/efeitos dos fármacos , Criação de Animais Domésticos/métodos , Fenômenos Fisiológicos da Nutrição Animal/efeitos dos fármacos , Animais , Galinhas/metabolismo , Citrobacter/metabolismo , Dieta/veterinária , Suplementos Nutricionais/análise , Enterobacteriaceae/metabolismo , Íleo/efeitos dos fármacos , Íleo/metabolismo , Masculino , Ácido Fítico/metabolismo
14.
Mol Med Rep ; 23(2)2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33655320

RESUMO

Atezolizumab can reduce immunosuppression caused by T lymphocyte apoptosis in various cancer types. The current study aimed to investigate whether this drug can also alleviate immunosuppression during sepsis. For that purpose, a C57BL/6 mouse sepsis model was generated. Mice were randomly assigned to three groups: Sham, cecal ligation and puncture (CLP) and atezolizumab groups. Atezolizumab was administered in vivo by intraperitoneal injection. The expression of programmed death ligand­1 (PD­L1) on neutrophils and programmed death­1 (PD­1) on T lymphocytes was evaluated, and endotoxin concentration, intestinal permeability, ileum histopathological score and tight junction protein expression were assessed to determine the extent of disease in each group. The rate of T lymphocyte apoptosis was determined to assess the effects of atezolizumab on T lymphocyte apoptosis in vivo and in vitro. Survival times were also recorded to compare mouse prognosis during sepsis. In the CLP group, the proportion of PD­L1+ neutrophils was significantly higher at 48, 72 and 96 h in blood, and at 24, 48, 72 and 96 h in bone marrow, compared with those of the sham group (P<0.05). The proportion of PD­1+ T lymphocytes was also upregulated at 72 h in blood. In the atezolizumab group, endotoxin concentration, intestinal permeability and ileum histopathological score were lower compared with those in the CLP group (P<0.05), whereas the expression of claudin­1 and occludin proteins on ileum was higher compared with that in the CLP group (P<0.05). Both in vivo and in vitro experiments indicated that the rate of T lymphocyte apoptosis following atezolizumab treatment was lower compared with that in the CLP group (P<0.05). Survival analysis demonstrated that mice in the atezolizumab group survived longer compared with those in the CLP group (P<0.05). The current study demonstrated that treatment with atezolizumab may be an effective method for treating immunosuppression induced by sepsis.


Assuntos
Anticorpos Monoclonais Humanizados/farmacologia , Íleo/patologia , Imunossupressão , Neutrófilos/imunologia , Sepse/tratamento farmacológico , Animais , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/uso terapêutico , Antígeno B7-H1 , Ceco/lesões , Claudina-1/genética , Modelos Animais de Doenças , Regulação da Expressão Gênica , Íleo/metabolismo , Injeções Intraperitoneais , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Ocludina/genética , Sepse/imunologia , Resultado do Tratamento
15.
Poult Sci ; 100(3): 100967, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33652524

RESUMO

The reduced use of antibiotics in poultry feed has led to the investigation of alternatives to antibiotics, and one such substitution is fermentable carbohydrates. Exogenous ß-glucanase (BGase) is commonly used in poultry fed barley-based diets to reduce digesta viscosity. The effects of hulless barley (HB) and BGase levels on ileal digesta soluble ß-glucan molecular weight, digestive tract characteristics, and performance of broiler chickens were determined. A total of 360 day-old broilers were housed in battery cages (4 birds per cage) and fed graded levels of high ß-glucan HB (CDC Fibar; 0, 30, and 60% replacing wheat) and BGase (Econase GT 200 P; 0, 0.01, and 0.1%) in a 3 × 3 factorial arrangement. Beta-glucan peak molecular weight in the ileal digesta was lower with 30 and 60 than 0% HB, whereas the peak decreased with increasing BGase. The weight average molecular weight was lower at 0.1 than 0% BGase in wheat diets, whereas in HB diets, it was lower at 0.01 and 0.1 than 0% BGase. The maximum molecular weight was lower with 0.01 and 0.1 than 0% BGase regardless of the HB level. The maximum molecular weight was lower with HB than wheat at 0 or 0.01% BGase. Overall, empty weights and lengths of digestive tract sections increased with increasing HB, but there was no BGase effect. Hulless barley decreased the duodenum and jejunum contents, whereas increasing the gizzard (diets with BGase), ileum, and colon contents. The jejunum and small intestine contents decreased with increasing BGase. Ileal and colon pH increased with increasing HB, but there was no BGase effect. Treatment effects were minor on short-chain fatty acids levels and performance. In conclusion, exogenous BGase depolymerized the ileal digesta soluble ß-glucan in broiler chickens in a dose-dependent manner. Overall, feed efficiency was impaired by increasing HB levels. However, HB and BGase did not affect carbohydrate fermentation in the ileum and ceca, although BGase decreased ileal viscosity and improved feed efficiency at the 0.1% dietary level.


Assuntos
Galinhas , Dextranase , Dieta , Trato Gastrointestinal , Hordeum , beta-Glucanas , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal , Animais , Galinhas/crescimento & desenvolvimento , Galinhas/metabolismo , Dextranase/metabolismo , Dextranase/farmacologia , Dieta/veterinária , Digestão , Trato Gastrointestinal/metabolismo , Hordeum/classificação , Hordeum/metabolismo , Íleo/metabolismo , Peso Molecular , beta-Glucanas/química
16.
Am J Physiol Cell Physiol ; 320(5): C794-C805, 2021 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-33760661

RESUMO

The development of alternative in vitro culture methods has increased in the last decade as three-dimensional organoids of various tissues, including those of the small and large intestines. Due to their multicellular composition, organoids offer advantages over traditionally used immortalized or primary cell lines. However, organoids must be accurate models of their tissues of origin. This study compared gene expression profiles with respect to markers of specific cell types (stem cells, enterocytes, goblet, and enteroendocrine cells) and barrier maturation (tight junctions) of colonoid and enteroid cultures with their tissues of origin and colonoids with enteroids. Colonoids derived from three healthy pigs formed multilobed structures with a monolayer of cells similar to the crypt structures in colonic tissue. Colonoid and enteroid gene expression signatures were more similar to those found for the tissues of their origin than to each other. However, relative to their derived tissues, organoids had increased gene expression levels of stem cell markers Sox9 and Lgr5 encoding sex-determining region Y-box 9 and leucine-rich repeat-containing G protein-coupled rector 5, respectively. In contrast, expression levels of Occl and Zo1 encoding occludin and zonula occludens 1, respectively, were decreased. Expression levels of the cell lineage markers Atoh1, Cga, and Muc2 encoding atonal homolog 1, chromogranin A, and mucin 2, respectively, were decreased in colonoids, whereas Sglt1 and Apn encoding sodium-glucose transporter 1 and aminopeptidase A, respectively, were decreased in enteroids. These results indicate colonoid and enteroid cultures were predominantly comprised of undifferentiated cell types with decreased barrier maturation relative to their tissues of origin.


Assuntos
Diferenciação Celular , Linhagem da Célula , Colo/fisiologia , Íleo/fisiologia , Mucosa Intestinal/fisiologia , Organoides/fisiologia , Animais , Biomarcadores/metabolismo , Proliferação de Células , Colo/citologia , Colo/metabolismo , Regulação da Expressão Gênica , Íleo/citologia , Íleo/metabolismo , Mucosa Intestinal/citologia , Mucosa Intestinal/metabolismo , Masculino , Organoides/citologia , Organoides/metabolismo , Fenótipo , Transdução de Sinais , Sus scrofa , Fatores de Tempo , Técnicas de Cultura de Tecidos , Transcriptoma
17.
J Appl Genet ; 62(2): 307-317, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33638812

RESUMO

Taiping chicken is indigenous chickens (Gallus gallus domesticus), which was one of China's excellent poultry species, is an excellent chicken in Gansu Province. As the problems caused by the overuse of antibiotics become more and more severe, people begin to look for ways to replace them. Among them, probiotics and fructo-oligosaccharides are the research hotspot to replace antibiotics. Probiotics and fructo-oligosaccharides can promote the absorption of nutrients, improve the ability to resist and prevent diseases, and improve the intestinal tissue morphology. In this study, we used RNA-Seq analysis to study the gene expression in ileum tissue after Taiping chicken was given probiotics and fructo-oligosaccharides. In total, 67 genes were differentially expressed in the ileum. Ten of the differently expressed genes were further validated by RT-qPCR. In addition, these differentially expressed genes were mainly enriched to tyrosine metabolism, AGE-RAGE signaling pathway in diabetic complications, phenylalanine metabolism, and pyrimidine metabolism. The results which this study provides contribute to our understanding application of probiotics and fructo-oligosaccharides in indigenous chickens production and provide a theoretical basis for the genetic development of indigenous chickens.


Assuntos
Galinhas/genética , Íleo/metabolismo , Oligossacarídeos/administração & dosagem , Probióticos , Transcriptoma , Ração Animal , Animais , China
18.
Am J Physiol Gastrointest Liver Physiol ; 320(4): G658-G674, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33566727

RESUMO

Necrotizing enterocolitis (NEC), a life-threatening intestinal disease, is becoming a larger proportionate cause of morbidity and mortality in premature infants. To date, therapeutic options remain elusive. Based on recent cell therapy studies, we investigated the effect of a human placental-derived stem cell (hPSC) therapy on intestinal damage in an experimental NEC rat pup model. NEC was induced in newborn Sprague-Dawley rat pups for 4 days via formula feeding, hypoxia, and LPS. NEC pups received intraperitoneal (ip) injections of either saline or hPSC (NEC-hPSC) at 32 and 56 h into NEC induction. At 4 days, intestinal macroscopic and histological damage, epithelial cell composition, and inflammatory marker expression of the ileum were assessed. Breastfed (BF) littermates were used as controls. NEC pups developed significant bowel dilation and fragility in the ileum. Further, NEC induced loss of normal villi-crypt morphology, disruption of epithelial proliferation and apoptosis, and loss of critical progenitor/stem cell and Paneth cell populations in the crypt. hPSC treatment improved macroscopic intestinal health with reduced ileal dilation and fragility. Histologically, hPSC administration had a significant reparative effect on the villi-crypt morphology and epithelium. In addition to a trend of decreased inflammatory marker expression, hPSC-NEC pups had increased epithelial proliferation and decreased apoptosis when compared with NEC littermates. Further, the intestinal stem cell and crypt niche that include Paneth cells, SOX9+ cells, and LGR5+ stem cells were restored with hPSC therapy. Together, these data demonstrate hPSC can promote epithelial healing of NEC intestinal damage.NEW & NOTEWORTHY These studies demonstrate a human placental-derived stem cell (hPSC) therapeutic strategy for necrotizing enterocolitis (NEC). In an experimental model of NEC, hPSC administration improved macroscopic intestinal health, ameliorated epithelial morphology, and supported the intestinal stem cell niche. Our data suggest that hPSC are a potential therapeutic approach to attenuate established intestinal NEC damage. Further, we show hPSC are a novel research tool that can be utilized to elucidate critical neonatal repair mechanisms to overcome NEC.


Assuntos
Apoptose , Proliferação de Células , Enterocolite Necrosante/cirurgia , Íleo/patologia , Mucosa Intestinal/patologia , Celulas de Paneth/patologia , Placenta/transplante , Transplante de Células-Tronco , Animais , Animais Recém-Nascidos , Células Cultivadas , Citocinas/genética , Citocinas/metabolismo , Modelos Animais de Doenças , Enterocolite Necrosante/genética , Enterocolite Necrosante/metabolismo , Enterocolite Necrosante/patologia , Feminino , Humanos , Íleo/metabolismo , Mediadores da Inflamação/metabolismo , Mucosa Intestinal/metabolismo , Celulas de Paneth/metabolismo , Placenta/citologia , Gravidez , Ratos Sprague-Dawley , Receptores Acoplados a Proteínas G/metabolismo , Fatores de Transcrição SOX9 , Nicho de Células-Tronco , Cicatrização
19.
Poult Sci ; 100(2): 1178-1191, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33518076

RESUMO

The gastrointestinal health of poultry can be impacted by a variety of factors including their environment. As egg production moves from conventional cage housing (CC) toward cage-free housing (CF), it is important to understand this impact on intestinal health. This study was conducted to determine if housing type impacted intestinal permeability, morphology, and microbial communities in commercial hens across housing systems. Hens were randomly selected from 2 rooms of CC (n = 25) and CF (n = 25) at a commercial facility. Birds were given fluorescein isothiocyanate dextran (FITC-D) by oral gavage to measure intestinal permeability. Jejunal and ileal samples were collected to evaluate villus height, crypt depth, and their ratio. Ileal contents were collected for bacterial DNA isolation and 16S rRNA gene sequencing. Serum FITC-D was similar between housing type (P = 0.709). Hens housed in the CF had increased jejunal villus height and crypt depth compared with hens from the CC (P < 0.002). Hens from the CC tended to have a greater villus height to crypt depth ratio in both the jejunum and ileum compared with the CF (P = 0.064; P = 0.091, respectively). Microbial community diversity measurements favored hens housed in the CC as ileal contents tended to have increased species richness (P = 0.059), had greater alpha diversity (P = 0.044), and had an increased number of over represented operational taxonomic units (46/64), including Romboutsia sp. (30.80%), Lactobacillus kitasatonis (17.16%), and Lactobacillus aviarius (11.15%). Correlations between microbial communities with intestinal traits identified significant association with the greatest number of correlations with FITC-D and ileal morphology. Many of these correlations identified microbial communities associated with expected traits; thus, providing limited functional data to microbial communities with limited information. The greater number of correlations of ileal morphology with ileal microbial communities suggesting local microbial communities contribute to the intestinal environment distant. In this limited study, several parameters favored hens from CC suggesting an advantage of this system for intestinal health. However, the lower intestinal health parameters observed in CF were not at levels to indicate detrimental effects.


Assuntos
Bactérias/classificação , Galinhas , Microbioma Gastrointestinal , Abrigo para Animais/classificação , Íleo/metabolismo , Íleo/microbiologia , Animais , Feminino , Íleo/anatomia & histologia , Jejuno/anatomia & histologia , Jejuno/microbiologia , Permeabilidade , RNA Ribossômico 16S/genética
20.
Pediatr Surg Int ; 37(3): 301-309, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33566163

RESUMO

PURPOSE: Necrotizing enterocolitis (NEC) is a devastating gastrointestinal disease. Amniotic fluid stem cells (AFSC) improve NEC injury but human translation remains difficult. We aimed to evaluate the use of extracellular vesicles (EV) derived from human AFSC. METHODS: Human AFSC (hAFSC) were cultured according to the protocol (Celprogen Inc., California, U.S.A.). Conditioned medium was obtained, ultra-centrifuged, and EV were suspended in phosphate-buffered saline (PBS). C57BL/6 pups were grouped into: (1) breast-fed (Control, n = 11); (2) NEC + placebo (NEC + PBS; n = 10); and (3) NEC + treatment (NEC + EV; n = 11). NEC was induced post-natal days P5-9 by (A) gavage feeding hyperosmolar formula; (B) hypoxia for 10 min; and (C) lipopolysaccharide. Intra-peritoneal injections of PBS or hAFSC-EV were given on P6-7. All animals were sacrificed on P9 and terminal ileum harvested. RESULTS: hAFSC-EV administration reduced intestinal injury (p = 0.0048), NEC incidence (score ≥ 2), and intestinal inflammation (IL-6 p < 0.0001; TNF-α p < 0.0001). Intestinal stem cell expression (Lgr5 +) and cellular proliferation (Ki67) were enhanced above control levels following hAFSC-EV administration (Lgr5 p = 0.0003; Ki67 p < 0.0001). CONCLUSION: hAFSC-EV administration reduced intestinal NEC injury and inflammation while increasing stem cell expression and cellular proliferation. hAFSC-EV administration may induce similar beneficial effects to exogenous stem cells.


Assuntos
Líquido Amniótico/citologia , Enterocolite Necrosante/metabolismo , Vesículas Extracelulares/metabolismo , Animais , Animais Recém-Nascidos , Proliferação de Células , Modelos Animais de Doenças , Enterocolite Necrosante/terapia , Feminino , Humanos , Íleo/metabolismo , Recém-Nascido , Doenças do Recém-Nascido , Inflamação/metabolismo , Intestinos , Camundongos , Camundongos Endogâmicos C57BL , Células-Tronco/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
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