Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 6 de 6
Filtrar
Mais filtros

Base de dados
Tipo de documento
Intervalo de ano de publicação
1.
J Infect Dis ; 213(11): 1846-56, 2016 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-27067195

RESUMO

Dietary lipids modulate immunity, yet the means by which specific fatty acids affect infectious disease susceptibility remains unclear. Deciphering lipid-induced immunity is critical to understanding the balance required for protecting against pathogens while avoiding chronic inflammatory diseases. To understand how specific lipids alter susceptibility to enteric infection, we fed mice isocaloric, high-fat diets composed of corn oil (rich in n-6 polyunsaturated fatty acids [n-6 PUFAs]), olive oil (rich in monounsaturated fatty acids), or milk fat (rich in saturated fatty acids) with or without fish oil (rich in n-3 PUFAs). After 5 weeks of dietary intervention, mice were challenged with Citrobacter rodentium, and pathological responses were assessed. Olive oil diets resulted in little colonic pathology associated with intestinal alkaline phosphatase, a mucosal defense factor that detoxifies lipopolysaccharide. In contrast, while both corn oil and milk fat diets resulted in inflammation-induced colonic damage, only milk fat induced compensatory protective responses, including short chain fatty acid production. Fish oil combined with milk fat, unlike unsaturated lipid diets, had a protective effect associated with intestinal alkaline phosphatase activity. Overall, these results reveal that dietary lipid type, independent of the total number of calories associated with the dietary lipid, influences the susceptibility to enteric damage and the benefits of fish oil during infection.


Assuntos
Citrobacter rodentium , Gorduras na Dieta/uso terapêutico , Ingestão de Energia , Infecções por Enterobacteriaceae/dietoterapia , Animais , Células CACO-2 , Colo/microbiologia , Óleo de Milho/administração & dosagem , Óleo de Milho/uso terapêutico , Dieta Hiperlipídica , Gorduras na Dieta/imunologia , Suscetibilidade a Doenças , Infecções por Enterobacteriaceae/imunologia , Infecções por Enterobacteriaceae/prevenção & controle , Feminino , Óleos de Peixe/uso terapêutico , Humanos , Lipopolissacarídeos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Leite , Azeite de Oliva/administração & dosagem , Azeite de Oliva/uso terapêutico , Fosforilação , Resultado do Tratamento
2.
World J Gastroenterol ; 20(42): 15650-6, 2014 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-25400448

RESUMO

Intestinal alkaline phosphatase (IAP) plays an essential role in intestinal homeostasis and health through interactions with the resident microbiota, diet and the gut. IAP's role in the intestine is to dephosphorylate toxic microbial ligands such as lipopolysaccharides, unmethylated cytosine-guanosine dinucleotides and flagellin as well as extracellular nucleotides such as uridine diphosphate. IAP's ability to detoxify these ligands is essential in protecting the host from sepsis during acute inflammation and chronic inflammatory conditions such as inflammatory bowel disease. Also important in these complications is IAP's ability to regulate the microbial ecosystem by forming a complex relationship between microbiota, diet and the intestinal mucosal surface. Evidence reveals that diet alters IAP expression and activity and this in turn can influence the gut microbiota and homeostasis. IAP's ability to maintain a healthy gastrointestinal tract has accelerated research on its potential use as a therapeutic agent against a multitude of diseases. Exogenous IAP has been shown to have beneficial effects when administered during ulcerative colitis, coronary bypass surgery and sepsis. There are currently a handful of human clinical trials underway investigating the effects of exogenous IAP during sepsis, rheumatoid arthritis and heart surgery. In light of these findings IAP has been marked as a novel agent to help treat a variety of other inflammatory and infectious diseases. The purpose of this review is to highlight the essential characteristics of IAP in protection and maintenance of intestinal homeostasis while addressing the intricate interplay between IAP, diet, microbiota and the intestinal epithelium.


Assuntos
Fosfatase Alcalina/metabolismo , Bactérias/imunologia , Dieta , Imunidade nas Mucosas , Intestinos , Fosfatase Alcalina/uso terapêutico , Animais , Anti-Inflamatórios/uso terapêutico , Doença Crônica , Proteínas Ligadas por GPI/metabolismo , Proteínas Ligadas por GPI/uso terapêutico , Homeostase , Interações Hospedeiro-Patógeno , Humanos , Inflamação/enzimologia , Inflamação/imunologia , Inflamação/microbiologia , Doenças Inflamatórias Intestinais/enzimologia , Doenças Inflamatórias Intestinais/imunologia , Doenças Inflamatórias Intestinais/microbiologia , Intestinos/efeitos dos fármacos , Intestinos/enzimologia , Intestinos/imunologia , Intestinos/microbiologia , Transdução de Sinais
3.
PLoS One ; 8(8): e70248, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23936397

RESUMO

PGC-1α, a transcriptional coactivator, controls inflammation and mitochondrial gene expression in insulin-sensitive tissues following exercise intervention. However, attributing such effects to PGC-1α is counfounded by exercise-induced fluctuations in blood glucose, insulin or bodyweight in diabetic patients. The goal of this study was to investigate the role of PGC-1α on inflammation and mitochondrial protein expressions in aging db/db mice hearts, independent of changes in glycemic parameters. In 8-month-old db/db mice hearts with diabetes lasting over 22 weeks, short-term, moderate-intensity exercise upregulated PGC-1α without altering body weight or glycemic parameters. Nonetheless, such a regimen lowered both cardiac (macrophage infiltration, iNOS and TNFα) and systemic (circulating chemokines and cytokines) inflammation. Curiously, such an anti-inflammatory effect was also linked to attenuated expression of downstream transcription factors of PGC-1α such as NRF-1 and several respiratory genes. Such mismatch between PGC-1α and its downstream targets was associated with elevated mitochondrial membrane proteins like Tom70 but a concurrent reduction in oxidative phosphorylation protein expressions in exercised db/db hearts. As mitochondrial oxidative stress was predominant in these hearts, in support of our in vivo data, increasing concentrations of H2O2 dose-dependently increased PGC-1α expression while inhibiting expression of inflammatory genes and downstream transcription factors in H9c2 cardiomyocytes in vitro. We conclude that short-term exercise-induced oxidative stress may be key in attenuating cardiac inflammatory genes and impairing PGC-1α mediated gene transcription of downstream transcription factors in type 2 diabetic hearts at an advanced age.


Assuntos
Envelhecimento/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Proteínas de Membrana/metabolismo , Membranas Mitocondriais/metabolismo , Miocárdio/metabolismo , Condicionamento Físico Animal , Fatores de Transcrição/metabolismo , Envelhecimento/patologia , Animais , Respiração Celular , DNA Mitocondrial/genética , Diabetes Mellitus Tipo 2/enzimologia , Diabetes Mellitus Tipo 2/patologia , Inflamação/genética , Inflamação/metabolismo , Inflamação/patologia , Masculino , Camundongos , Miocárdio/enzimologia , Miocárdio/patologia , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Fosforilação Oxidativa , Estresse Oxidativo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Fatores de Transcrição/genética , Ativação Transcricional , Regulação para Cima
4.
PLoS One ; 8(2): e55468, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23405155

RESUMO

Clinically, excessive ω-6 polyunsaturated fatty acid (PUFA) and inadequate ω-3 PUFA have been associated with enhanced risks for developing ulcerative colitis. In rodent models, ω-3 PUFAs have been shown to either attenuate or exacerbate colitis in different studies. We hypothesized that a high ω-6: ω-3 PUFA ratio would increase colitis susceptibility through the microbe-immunity nexus. To address this, we fed post-weaned mice diets rich in ω-6 PUFA (corn oil) and diets supplemented with ω-3 PUFA (corn oil+fish oil) for 5 weeks. We evaluated the intestinal microbiota, induced colitis with Citrobacter rodentium and followed disease progression. We found that ω-6 PUFA enriched the microbiota with Enterobacteriaceae, Segmented Filamentous Bacteria and Clostridia spp., all known to induce inflammation. During infection-induced colitis, ω-6 PUFA fed mice had exacerbated intestinal damage, immune cell infiltration, prostaglandin E2 expression and C. rodentium translocation across the intestinal mucosae. Addition of ω-3 PUFA on a high ω-6 PUFA diet, reversed inflammatory-inducing microbial blooms and enriched beneficial microbes like Lactobacillus and Bifidobacteria, reduced immune cell infiltration and impaired cytokine/chemokine induction during infection. While, ω-3 PUFA supplementation protected against severe colitis, these mice suffered greater mortality associated with sepsis-related serum factors such as LPS binding protein, IL-15 and TNF-α. These mice also demonstrated decreased expression of intestinal alkaline phosphatase and an inability to dephosphorylate LPS. Thus, the colonic microbiota is altered differentially through varying PUFA composition, conferring altered susceptibility to colitis. Overall, ω-6 PUFA enriches pro-inflammatory microbes and augments colitis; but prevents infection-induced systemic inflammation. In contrast, ω-3 PUFA supplementation reverses the effects of the ω-6 PUFA diet but impairs infection-induced responses resulting in sepsis. We conclude that as an anti-inflammatory agent, ω-3 PUFA supplementation during infection may prove detrimental when host inflammatory responses are critical for survival.


Assuntos
Colite/induzido quimicamente , Ácidos Graxos Ômega-3/farmacologia , Ácidos Graxos Ômega-6/farmacologia , Óleos de Peixe/farmacologia , Lipopolissacarídeos/farmacologia , Sepse/microbiologia , Fosfatase Alcalina/metabolismo , Animais , Citrobacter rodentium/metabolismo , Colite/metabolismo , Colite/microbiologia , Dieta , Suplementos Nutricionais , Dinoprostona/metabolismo , Infecções por Enterobacteriaceae/metabolismo , Infecções por Enterobacteriaceae/microbiologia , Ácidos Graxos Ômega-3/toxicidade , Ácidos Graxos Ômega-6/toxicidade , Feminino , Interleucina-15/metabolismo , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiologia , Camundongos , Camundongos Endogâmicos C57BL , Sepse/induzido quimicamente , Sepse/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
5.
Br J Nutr ; 110(3): 515-23, 2013 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-23298440

RESUMO

Controversies have emerged regarding the beneficial v. detrimental effects of dietary n-6 PUFA. The alteration of the intestinal microbiota, a phenomenon termed dysbiosis, occurs during several chronic inflammatory diseases, but has not been well studied in an aged population. With present 'Western' diets predominantly composed of n-6 PUFA, we hypothesised that PUFA-rich diets cause intestinal dysbiosis in an aged population. C57BL/6 mice (aged 2 years) were fed a high-fat (40% energy), isoenergetic and isonitrogenous diet composed of rapeseed oil, maize oil or maize oil supplemented with fish oil. We examined ileal microbiota using fluorescence in situ hybridisation and stained tissues by immunofluorescence for the presence of immune cells and oxidative stress. We observed that feeding high-fat diets rich in n-6 PUFA promoted bacterial overgrowth but depleted microbes from the Bacteroidetes and Firmicutes phyla. This corresponded with increased body mass and infiltration of macrophages and neutrophils. Fish oil supplementation (rich in long-chain n-3 PUFA like DHA and EPA) restored the microbiota and inflammatory cell infiltration and promoted regulatory T-cell recruitment. However, fish oil supplementation was associated with increased oxidative stress, evident by the increased presence of 4-hydroxynonenal, a product of lipid peroxidation. These results suggest that an n-6 PUFA-rich diet can cause dysbiosis and intestinal inflammation in aged mice. However, while fish oil supplementation on an n-6 PUFA diet reverses dysbiosis, the combination of n-6 and n-3 PUFA, like DHA/EPA, leads to increased oxidative stress, which could exacerbate gastrointestinal disorders in the elderly.


Assuntos
Bactérias/efeitos dos fármacos , Dieta/efeitos adversos , Gorduras na Dieta/efeitos adversos , Ácidos Graxos Ômega-6/efeitos adversos , Íleo/efeitos dos fármacos , Inflamação/etiologia , Enteropatias/etiologia , Animais , Bactérias/crescimento & desenvolvimento , Bactérias/imunologia , Peso Corporal/efeitos dos fármacos , Dieta Hiperlipídica , Gorduras na Dieta/farmacologia , Gorduras na Dieta/uso terapêutico , Suplementos Nutricionais , Feminino , Óleos de Peixe/efeitos adversos , Óleos de Peixe/uso terapêutico , Íleo/imunologia , Íleo/microbiologia , Inflamação/imunologia , Inflamação/microbiologia , Enteropatias/imunologia , Enteropatias/microbiologia , Peroxidação de Lipídeos , Macrófagos/imunologia , Macrófagos/metabolismo , Metagenoma/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Infiltração de Neutrófilos , Estresse Oxidativo , Linfócitos T Reguladores/metabolismo
6.
Nutrients ; 4(8): 1095-119, 2012 08.
Artigo em Inglês | MEDLINE | ID: mdl-23016134

RESUMO

The gastrointestinal (GI) microbiota is the collection of microbes which reside in the GI tract and represents the largest source of non-self antigens in the human body. The GI tract functions as a major immunological organ as it must maintain tolerance to commensal and dietary antigens while remaining responsive to pathogenic stimuli. If this balance is disrupted, inappropriate inflammatory processes can result, leading to host cell damage and/or autoimmunity. Evidence suggests that the composition of the intestinal microbiota can influence susceptibility to chronic disease of the intestinal tract including ulcerative colitis, Crohn's disease, celiac disease and irritable bowel syndrome, as well as more systemic diseases such as obesity, type 1 diabetes and type 2 diabetes. Interestingly, a considerable shift in diet has coincided with increased incidence of many of these inflammatory diseases. It was originally believed that the composition of the intestinal microbiota was relatively stable from early childhood; however, recent evidence suggests that diet can cause dysbiosis, an alteration in the composition of the microbiota, which could lead to aberrant immune responses. The role of the microbiota and the potential for diet-induced dysbiosis in inflammatory conditions of the GI tract and systemic diseases will be discussed.


Assuntos
Bactérias/classificação , Dieta , Intestinos/microbiologia , Doença Celíaca/microbiologia , Diabetes Mellitus Tipo 1/microbiologia , Diabetes Mellitus Tipo 2/microbiologia , Hipersensibilidade Alimentar , Homeostase , Humanos , Inflamação , Doenças Inflamatórias Intestinais/microbiologia , Síndrome Metabólica/microbiologia , Obesidade/microbiologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA