RESUMO
In this systematic review, we critically evaluated human clinical trials that assessed the effects of dietary fat quality on metabolic endotoxaemia. The studies were selected from three databases (PubMed, Scopus and Cochrane Library), and the keywords were defined according to the Medical Subject Headings indexing terminology. Two authors searched independently, according to the pre-defined selection criteria. Quality and risk assessment of bias for each selected study were also evaluated. The results of the included studies demonstrated associations between higher SFA intake and increased postprandial lipopolysaccharide (LPS) concentrations. On the other hand, after the consumption of PUFA, bloodstream LPS concentrations were lower. However, in none of the long-term studies, the consumption of dietary fats did not seem to exert effects on LPS concentration. Hence, SFA seem to act as a risk factor for transient increase in endotoxaemia, while PUFA demonstrated exerting a protective effect. Taken together, the evidence suggests that the dietary fatty acid profile may influence bloodstream endotoxin concentrations through modulation of factors such LPS clearance, alkaline phosphatase activity, bile acid metabolism, intestinal permeability and intestinal microbiota composition.
Assuntos
Dieta/efeitos adversos , Gorduras na Dieta/farmacologia , Endotoxemia/etiologia , Ácidos Graxos/farmacologia , Período Pós-Prandial/efeitos dos fármacos , Proteínas de Fase Aguda , Adulto , Proteínas de Transporte/sangue , Ensaios Clínicos como Assunto , Ingestão de Alimentos/fisiologia , Feminino , Humanos , Lipopolissacarídeos/sangue , Masculino , Glicoproteínas de Membrana/sangue , Pessoa de Meia-Idade , Fenômenos Fisiológicos da NutriçãoRESUMO
High-fat diet increase two to three times the plasma lipopolysaccharide (LPS) levels and induce subclinical inflammation. Diet can modify gene expression due to epigenetic processes related to MicroRNAs (miRNAs). MicroRNAs (miRNAs) play important role in the post-transcriptional mechanisms involved in regulation of expression of genes related to the inflammatory response. Also, diet can indirectly induce post-transcriptional regulation of gene expression by miRNAs, which may affect the risk for the development of chronic diseases. OBJECTIVE: This study investigated the effect of high-fat high-saturated meal ingestion on plasma miRNA expression and LPS levels during the postprandial period in healthy women. METHODS: An interventional study was carried out in which a high-fat breakfast (1067.45 kcal), composed mainly of saturated fatty acids (56 g), and 500 mL of water, was offered. Blood samples were collected at baseline and 1, 3 and 5 h after meal intake. The studied population consisted of healthy women (n = 11), aged between 20 and 40 years, and body mass index (BMI) between 18.5 and 25 kg/m2. Plasma levels of lipid profile, cytokines, adhesion molecules, and LPS were measured at the 3 time points. A profile of 752 human plasma miRNA expression was analyzed by real-time PCR assay. These analyzes were performed for all blood collection time-points. RESULTS: Expression profile analysis revealed 33 differentially expressed plasma circulating miRNAs compared to that of the control group. MiR-145-5p and miR-200 were differentially modulated in all time-points post meal consumption. In addition, there was a significant increase in plasma LPS, triglycerides, myristic and palmitic saturated fatty acids levels at the 3 time-points in comparison with the control basal levels. We also observed increased levels of the plasma tumor necrosis factor alpha (TNF-α) cytokine and the vascular cell adhesion molecule 1 (VCAM-1) levels after 5 h post meal ingestion. CONCLUSION: Ingestion of high-fat high-saturated meal was able to induce metabolic endotoxemia and increase the expression of pro-inflammatory molecules such as TNF-alpha and VCAM-1, as well as modulating circulating miRNAs possibly controlling inflammatory and lipid metabolism proteins at the postprandial period.
Assuntos
MicroRNA Circulante/sangue , Dieta Hiperlipídica/efeitos adversos , Endotoxemia/sangue , Endotoxemia/etiologia , Adulto , Brasil , Dieta Hiperlipídica/métodos , Feminino , Humanos , Inflamação/sangue , Inflamação/etiologia , Lipopolissacarídeos/sangue , Adulto JovemRESUMO
INTRODUCTION: Nonalcoholic steatohepatitis (NASH) is characterized by the presence of steatosis, inflammation, and ballooning degeneration of hepatocytes, with or without fibrosis. The prevalence of NASH has increased with the obesity epidemic, but its etiology is multifactorial. The current studies suggest the role of gut microbiota in the development and progression of NASH. The aim is to review the studies that investigate the relationship between gut microbiota and NASH. These review also discusses the pathophysiological mechanisms and the influence of diet on the gut-liver axis. RESULT: The available literature has proposed mechanisms for an association between gut microbiota and NASH, such as: modification energy homeostasis, lipopolysaccharides (LPS)-endotoxemia, increased endogenous production of ethanol, and alteration in the metabolism of bile acid and choline. There is evidence to suggest that NASH patients have a higher prevalence of bacterial overgrowth in the small intestine and changes in the composition of the gut microbiota. However, there is still a controversy regarding the microbiome profile in this population. The abundance of Bacteroidetes phylum may be increased, decreased, or unaltered in NASH patients. There is an increase in the Escherichia and Bacteroides genus. There is depletion of certain taxa, such as Prevotella and Faecalibacterium. CONCLUSION: Although few studies have evaluated the composition of the gut microbiota in patients with NASH, it is observed that these individuals have a distinct gut microbiota, compared to the control groups, which explains, at least in part, the genesis and progression of the disease through multiple mechanisms. Modulation of the gut microbiota through diet control offers new challenges for future studies.
Assuntos
Disbiose/fisiopatologia , Medicina Baseada em Evidências , Microbioma Gastrointestinal , Fígado/fisiopatologia , Modelos Biológicos , Hepatopatia Gordurosa não Alcoólica/etiologia , Animais , Ácidos e Sais Biliares/metabolismo , Colina/metabolismo , Dieta/efeitos adversos , Progressão da Doença , Disbiose/imunologia , Disbiose/metabolismo , Disbiose/microbiologia , Endotoxemia/etiologia , Endotoxemia/imunologia , Endotoxemia/microbiologia , Endotoxemia/fisiopatologia , Ingestão de Energia , Metabolismo Energético , Etanol/metabolismo , Fermentação , Microbioma Gastrointestinal/imunologia , Humanos , Lipopolissacarídeos/biossíntese , Lipopolissacarídeos/toxicidade , Fígado/imunologia , Fígado/metabolismo , Hepatopatia Gordurosa não Alcoólica/imunologia , Hepatopatia Gordurosa não Alcoólica/microbiologia , Hepatopatia Gordurosa não Alcoólica/fisiopatologiaRESUMO
Dietary fat strongly affects human health by modulating gut microbiota composition and low-grade systemic inflammation. High-fat diets have been implicated in reduced gut microbiota richness, increased Firmicutes to Bacteroidetes ratio, and several changes at family, genus and species levels. Saturated (SFA), monounsaturated (MUFA), polyunsaturated (PUFA) and conjugated linolenic fatty acids share important pathways of immune system activation/inhibition with gut microbes, modulating obesogenic and proinflammatory profiles. Mechanisms that link dietary fat, gut microbiota and obesity are mediated by increased intestinal permeability, systemic endotoxemia, and the activity of the endocannabinoid system. Although the probiotic therapy could be a complementary strategy to improve gut microbiota composition, it did not show permanent effects to treat fat-induced dysbiosis. Based upon evidence to date, we believe that high-fat diets and SFA consumption should be avoided, and MUFA and omega-3 PUFA intake should be encouraged in order to regulate gut microbiota and inflammation, promoting body weight/fat control.
Assuntos
Dieta Hiperlipídica/efeitos adversos , Disbiose/etiologia , Endotoxemia/etiologia , Enterite/etiologia , Medicina Baseada em Evidências , Intestinos/imunologia , Obesidade/etiologia , Animais , Disbiose/dietoterapia , Disbiose/microbiologia , Disbiose/fisiopatologia , Endotoxemia/imunologia , Endotoxemia/microbiologia , Endotoxemia/prevenção & controle , Enterite/imunologia , Enterite/microbiologia , Enterite/prevenção & controle , Microbioma Gastrointestinal , Humanos , Intestinos/microbiologia , Intestinos/fisiopatologia , Obesidade/imunologia , Obesidade/microbiologia , Obesidade/fisiopatologia , Permeabilidade , Probióticos/uso terapêutico , Simbióticos/administração & dosagem , Aumento de PesoRESUMO
Chronic inflammation is closely linked to several complications of chronic kidney disease (CKD), such as vascular calcification, accelerated atherosclerosis, loss of appetite, insulin resistance, increased muscle catabolism and anemia. As a consequence, inflammation is a predictor of mortality in this group of patients. Specific causes of the activation of the immune system in CKD are largely unknown. Endotoxin (ET) release to the circulation represents a potentially important target for interventions aiming to reduce mortality in CKD patients. In this minireview, we propose that there are several potential sources of endotoxemia in CKD and that gut translocation, leading to the generation of ligands of the innate immune response, represents a potentially reversible cause. Prevention of endotoxemia, through treating foci of ET (periodontal disease, catheters, vascular access) or reducing translocation from the gut, will potentially reduce the inflammatory response.
Assuntos
Endotoxemia/etiologia , Falência Renal Crônica/complicações , Animais , Endotoxemia/imunologia , Endotoxemia/patologia , Trato Gastrointestinal/imunologia , Trato Gastrointestinal/metabolismo , Trato Gastrointestinal/patologia , Humanos , Inflamação/etiologia , Inflamação/mortalidade , Inflamação/patologia , Falência Renal Crônica/mortalidade , Falência Renal Crônica/patologiaRESUMO
The aim of the present study was to determine whether the transient receptor potential vanilloid (TRPV1) receptor protein as well as the calcitonin gene-related peptide (CGRP) content could be enhanced after the i.p. administration of 5 mg/kg lipopolysaccharide (LPS) to Sprague-Dawley rats. In tongue tissue, used as a representative model of TRPV1 receptors expression, there was a significant increase in the abundance of TRPV1 receptor protein 6 h after LPS administration. In mesenteric arteries, the density of the CGRP-positive nerves as well as the release of CGRP induced by 10 microM anandamide was also significantly increased 6 h after LPS administration. The relaxant responses induced by anandamide in mesenteric beds isolated from either untreated or LPS-treated rats were abolished after a 2 h exposure to 10 microM capsaicin. Moreover, anandamide-induced relaxations of untreated mesenteries were potentiated by the protein kinase C (PKC) activator phorbol 12-myristate 13-acetate (PMA, 0.1 microM), but not by its inactive analogue 4alpha-phorbol (0.1 microM). The potentiation of anandamide effects caused by the PKC activator was accompanied by a significant increase in the overflow of CGRP induced by anandamide in the untreated rats. It is proposed that the overexpression of the TRPV1 receptors and the increased content of CGRP could contribute to the enhancement of anandamide effects during the endotoxemic shock. An eventual phosphorylation event linked to the overflow of CGRP could also participate in the enhanced relaxation caused by anandamide in endotoxemia.
Assuntos
Peptídeo Relacionado com Gene de Calcitonina/biossíntese , Endotoxemia/metabolismo , Canais de Cátion TRPV/biossíntese , Animais , Ácidos Araquidônicos/farmacologia , Endocanabinoides , Endotoxemia/etiologia , Lipopolissacarídeos , Masculino , Mesentério/efeitos dos fármacos , Mesentério/fisiologia , Norepinefrina/farmacologia , Forbóis/farmacologia , Alcamidas Poli-Insaturadas/farmacologia , Proteína Quinase C/metabolismo , Ratos , Ratos Sprague-Dawley , Acetato de Tetradecanoilforbol/farmacologia , Língua/metabolismo , Vasoconstritores/farmacologia , Vasodilatação/efeitos dos fármacosRESUMO
Various infections sensitize to lethal shock by promoting hyperactivation of macrophages to LPS stimulation. Although macrophages are thought to be deactivated upon contact with apoptotic cells during Trypanosoma cruzi infection, T. cruzi infection also sensitizes mice to endotoxemia. Herein, we studied the mechanisms of sensitization to endotoxemia in T. cruzi-infected mice in order to solve the paradox. Live (but not fixed) trypomastigotes from various stocks sensitized mice to endotoxemia. Mice deficient in glycolipid recognition (TLR2(-/-) and CD1d(-/-)) were sensitized by infection to challenge with LPS. Infected mice hyperproduced TNF and IL-10 upon LPS challenge. Infected TNF-R1(-/-), macrophage migration inhibitory factor (MIF)(-/-) and IFN-gamma(-/-) mice were lethally sensitized, but infected TNF-R1(-/-) mice administered anti-MIF survived shock with LPS. Macrophages from infected mice hyperproduced TNF in response to LPS stimulation and displayed increased expression of TLR4 compared to non-infected controls. Treatment with the PGE(2) synthesis inhibitor acetylsalicylic acid (AAS) in vivo reduced parasitemia and enhanced LPS-stimulated production of TNF by macrophages, but the effect was less in infected mice than in normal mice. Nevertheless, AAS treatment did not increase the susceptibility of infected mice to sublethal shock with LPS. Our results point to independent MIF and TNF/TNF-R1 lethal pathways and suggest a role for hyperactivated macrophages in T. cruzi-sensitized LPS-induced shock.
Assuntos
Doença de Chagas/imunologia , Endotoxemia/etiologia , Lipopolissacarídeos/imunologia , Macrófagos/imunologia , Animais , Aspirina/farmacologia , Inibidores de Ciclo-Oxigenase/farmacologia , Ensaio de Imunoadsorção Enzimática , Feminino , Citometria de Fluxo , Interleucina-10/biossíntese , Interleucina-10/imunologia , Fatores Inibidores da Migração de Macrófagos/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Camundongos , Trypanosoma cruzi , Fator de Necrose Tumoral alfa/biossíntese , Fator de Necrose Tumoral alfa/imunologiaRESUMO
A colonoscopia é um método diagnóstico seguro, apesar de invasivo, porém näo isento de complicaçöes. Os autores estudaram a possibilidade de translocaçäo bacteriana devido à realizaçäo de exame colonoscópico em 69 pacientes, tentando identificar possíveis condiçöes patológicas que possam concorrer para este fim e analisam aspectos relacionados com a fisiologia da translocaçäo bacteriana e com a necessidade do uso de antibióticos durante a realizaçäo do exame colonoscópico