RESUMEN
SCOPE: The study aims at identifying 1) the most sensitive compartment among plasma phospholipids, erythrocytes, and LDL for studying alpha-linolenic acid (ALA) conversion, and 2) whether ALA incorporation and conversion is saturable after administration of 13 C-labeled ALA-rich linseed oil (LO). The effect of a daily intake of 7 g nonlabeled LO (>43% w/w ALA) for 1 month after bolus administration of 7 g 13 C-labeled LO on day 1, and for 2 months after bolus administration of 7 g 13 C-labeled LO on day 1 and day 29 on 13 C-ALA incorporation and conversion into its higher homologs is investigated in healthy volunteers. METHODS AND RESULTS: Incorporation and conversion of LO-derived 13 C-labeled ALA is quantified by applying compartmental modeling. After bolus administration, a fractional conversion of approximately 30% from 13 C-ALA to 13 C-DHA is calculated as reflected by the LDL compartment. Treatment with LO for 8 weeks induces a mean reduction of 13 C-ALA conversion to 13 C-DHA by 48% as reflected by the LDL compartment, and a mean reduction of the 13 C-ALA incorporation into LDL by 46%. CONCLUSION: A 2-month dietary intake of a high dose of LO is sufficient to reach saturation of ALA incorporation into LDL particles, which are responsible for ALA distribution in the body.
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Aceite de Linaza/farmacocinética , Fosfolípidos/sangre , Ácido alfa-Linolénico/administración & dosificación , Ácido alfa-Linolénico/farmacocinética , Adulto , Peso Corporal/efectos de los fármacos , Isótopos de Carbono/farmacocinética , Ácidos Docosahexaenoicos/sangre , Ácidos Docosahexaenoicos/metabolismo , Ácido Eicosapentaenoico/sangre , Ácido Eicosapentaenoico/metabolismo , Eritrocitos/química , Eritrocitos/efectos de los fármacos , Ácidos Grasos Omega-3/análisis , Voluntarios Sanos , Humanos , Aceite de Linaza/farmacología , Lipoproteínas IDL/sangre , Masculino , Modelos BiológicosRESUMEN
Allergic bronchial asthma is a chronic inflammatory disease of the airways with an increasing incidence in Western societies. Exposure to allergens provokes recurrent attacks of breathlessness, airway hyperreactivity, wheezing, and coughing. For the early phase and milder forms of allergic asthma, dietary supplementation with long-chain polyunsaturated fatty acids (LCPUFA), predominantly fish oil-associated eicosapentaenoic (C20:5 ω-3) and docosahexaenoic acid (C22:6 ω-3), and distinct crop oil-derived fatty acids might provide a sustainable treatment strategy, as discussed in several studies. In addition to immune-controlling prostaglandins, leukotrienes, and thromboxanes, specialized proresolving mediators, such as lipoxins, resolvins, protectins, and maresins, are metabolized from different LCPUFA, which actively resolve inflammation. The aim of this review was to discuss the possible synergistic effects of ω-3 and ω-6 LCPUFA combinations concerning rebuilding fatty acid homeostasis in cellular membranes, modifying eicosanoid metabolic pathways, controlling inflammatory processes by focusing on resolving inflammation in the bronchoalveolar system on the cellular level, and helping to control clinical symptoms in bronchial asthma.
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Asma/dietoterapia , Suplementos Dietéticos , Ácidos Grasos Insaturados/administración & dosificación , Asma/inmunología , Asma/metabolismo , Ácidos Docosahexaenoicos/administración & dosificación , Sinergismo Farmacológico , Ácido Eicosapentaenoico/administración & dosificación , Aceites de Pescado/administración & dosificación , Humanos , Redes y Vías Metabólicas , Aceites de Plantas/administración & dosificaciónRESUMEN
Trout by-product hydrolysates, generated using trout pepsin, were characterized and studied in terms of their antibacterial effects against food contaminants and fish farming pathogens. After a hydrolysis time of 25 min, the hydrolysates demonstrated inhibitory activity against several gram-positive and gram-negative bacteria. The degree of hydrolysis (DH) was found to exert a considerable influence on antibacterial activity, with a significant increase in the observed inhibitory effect at the beginning of hydrolysis. The highest antibacterial activity was obtained at a DH of 30% (enzyme/protein ratio 0.04 U/mg of protein, enzyme activity 6.5 U/mg protein, hydrolysis conditions 37°C, pH 3.0). The highest antibacterial activity detected was against the fish farming bacteria Flavobacterium psychrophilum and Renibacterium salmoninarum, with minimal inhibition concentrations of 2mg/ml and 5mg/ml, respectively. The amino acid determination of the hydrolysate (DH 30%) revealed that lysine, leucine, alanine, arginine, glycine, aspartic acid and glutamic acid residues represented the major amino acids.
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Antibacterianos/química , Oncorhynchus mykiss/microbiología , Pepsina A/química , Animales , Manipulación de AlimentosRESUMEN
Previous studies have demonstrated that soyasaponin (SoSa) possesses anti-inflammatory properties in lipopolysaccharide (LPS)-stimulated immune cells by influencing the immune sensing of toll-like receptor (TLR) 4. The aim of this study was to investigate the immune modulatory effect of SoSa I on TLR2- and TLR4-induced inflammation within the monocytic MUTZ-3-cell model. MUTZ-3 cells were stimulated with gram-negative (Escherichia coli) or gram-positive (Staphylococcus aureus) bacteria or bacterial pathogen-associated molecular patterns (PAMPs) such as LPS or peptidoglycans (PGN) alone or in combination with SoSa I. Cell morphology was characterized by raster scanning and light microscopy. Cytokine production (IL-1ß, IL-6, TNF-α, IP-10, RANTES and IL-8) was measured by cytometric bead array and the expression of surface markers was assessed by flow cytometry. MUTZ-3 cells revealed a cell maturation-like alteration in morphology and increased expression of CD80, CD86, TLR2 and TLR4 after stimulation with either gram-negative and gram-positive bacteria or bacterial PAMPs. The addition of SoSa I suppressed pro-inflammatory cytokine and chemokine secretions in a dose-dependent manner regardless of TLR2 or TLR4 stimulation. Interestingly, E. coli- and S. aureus-induced inflammation was always inhibited better by SoSa I than that induced by LPS and PGN. Additionally, SoSa I reduced the expression of CD86 in PGN- or LPS-stimulated cells. This study demonstrated that the anti-inflammatory capacity of SoSa I is based on influencing both monocytic TLR2 and TLR4 and that SoSa I inhibits more effectively whole bacteria compared to solely LPS or PGN what points to a broader role of SoSa I in the down-regulation of inflammation.
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Antiinflamatorios no Esteroideos/farmacología , Antineoplásicos Fitogénicos/farmacología , Leucemia Mieloide Aguda/tratamiento farmacológico , Proteínas de Neoplasias/antagonistas & inhibidores , Ácido Oleanólico/análogos & derivados , Saponinas/farmacología , Receptor Toll-Like 2/antagonistas & inhibidores , Receptor Toll-Like 4/antagonistas & inhibidores , Antígeno B7-2/antagonistas & inhibidores , Antígeno B7-2/metabolismo , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Forma de la Célula/efectos de los fármacos , Quimiocinas/antagonistas & inhibidores , Quimiocinas/metabolismo , Citocinas/antagonistas & inhibidores , Citocinas/metabolismo , Endotoxinas/antagonistas & inhibidores , Endotoxinas/toxicidad , Humanos , Factores Inmunológicos/farmacología , Leucemia Mieloide Aguda/inmunología , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/patología , Monocitos/efectos de los fármacos , Monocitos/inmunología , Monocitos/metabolismo , Monocitos/patología , Proteínas de Neoplasias/agonistas , Proteínas de Neoplasias/metabolismo , Ácido Oleanólico/farmacología , Concentración Osmolar , Receptor Toll-Like 2/metabolismo , Receptor Toll-Like 4/metabolismoRESUMEN
The demand for health-promoting food ingredients rises within an increasing market worldwide. Different milks fermented with bacteria, yeasts, moulds or enzymes from animal, plant and microbial sources offer a broad range of possibilities to cover different health aspects with new bioactive components. By the fermentation process interesting ingredients are enriched and released from the matrix, like lactoferrin, micro-nutrients, CLA and sphingolipids or synthesized, such as exo-polysaccharides and bioactive peptides. In particular, milk derived bioactive peptides exert several important health-promoting activities, such as anti-hypertensive, anti-microbial, anti-oxidative, immune-modulatory, opioid and mineral-binding properties. Milk-fermentation processes with probiotic bacteria synergistically combine health supporting bacterial and milk ingredient aspects which include new therapeutic solutions concerning hypercholesterolemia, carcinogenic intoxications, treatment of diarrhea, reduction of intestine pathogens, and supporting natural immune defense. Especially, milk-proteins and associated bioactive peptides released during microbial or enzymatic fermentation of milk offer a broad spectrum of new functional properties, for instance anti-hypertensive, anti-microbial, anti-oxidative, immuno-modulatory, opioid and mineral-binding properties. This review aimed at discussing recent research activities on physiological purposes and technical process aspects of functional components from fermented milk with a specific focus on biofunctional peptides released from fermented milk proteins.
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Bacterias/metabolismo , Hongos/metabolismo , Proteínas de la Leche/farmacología , Leche/microbiología , Animales , Fermentación , Humanos , Leche/química , Leche/metabolismo , Proteínas de la Leche/química , Proteínas de la Leche/metabolismo , Péptidos/química , Péptidos/metabolismo , Péptidos/farmacologíaRESUMEN
The aim of this study was to determine whether oral supplementation with EPA/DHA (10.5 and 5.1% of fat, respectively) could improve the outcome of pulmonary P. aeruginosa infection in cftr(-/-) mice compared with wild-type (Wt) mice similarly treated. Because gender could influence the susceptibility of cftr-deficient mice, results were analyzed by gender. Wt and (-/-) mice were randomized for 6 wk to consume a control or EPA/DHA diet, infected with endotracheal injection of 5 × 10(7) CFU/mouse of P. aeruginosa, and killed 24 h later. Cftr(-/-) mice were more susceptible to infection than were Wt mice; (-/-) males had more neutrophils (P < 0.01) and a higher keratinocyte-derived chemokine (KC) level (P < 0.05), and (-/-) females had greater lung injury and mortality (P < 0.05). Female (-/-) mice were more susceptible than (-/-) males with a higher mortality and lung injury (P < 0.05). The EPA/DHA diet reduced neutrophil numbers and KC and IL-6 levels (P < 0.05) in (-/-) males and reduced mortality rate (P < 0.001), lung permeability, and IL-6 level (P < 0.05) in (-/-) females compared with (-/-) mice fed the control diet. These results were associated with a reduction in the pulmonary bacterial load (P < 0.05), an increase in the EPA/DHA concentration in cell membranes of (-/-) males and females (P < 0.01), and an increased weight gain only in males compared with (-/-) mice fed the control diet (P < 0.01). In conclusion, EPA/DHA improves the host resistance of (-/-) mice, although the beneficial effect differed in males and females.
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Regulador de Conductancia de Transmembrana de Fibrosis Quística/deficiencia , Fibrosis Quística/dietoterapia , Suplementos Dietéticos , Ácidos Grasos Omega-3/administración & dosificación , Neumonía Bacteriana/prevención & control , Infecciones por Pseudomonas/prevención & control , Animales , Líquido del Lavado Bronquioalveolar/inmunología , Fibrosis Quística/complicaciones , Regulador de Conductancia de Transmembrana de Fibrosis Quística/genética , Citocinas/metabolismo , Susceptibilidad a Enfermedades , Femenino , Humanos , Mediadores de Inflamación/metabolismo , Pulmón/fisiopatología , Masculino , Ratones , Ratones de la Cepa 129 , Ratones Endogámicos C57BL , Ratones Endogámicos CFTR , Ratones Noqueados , Infecciones Oportunistas/prevención & control , Neumonía Bacteriana/microbiología , Neumonía Bacteriana/fisiopatología , Infecciones por Pseudomonas/microbiología , Infecciones por Pseudomonas/fisiopatología , Factores SexualesRESUMEN
UNLABELLED: RATIO: Asthma is a major public health problem, with bronchial inflammation as the therapeutic target. The role of dietary fish oil derived polyunsaturated fatty acids (PUFAs) in allergic inflammation is controversial. Most asthmatics suffer from mild disease and non-pharmacologic interventions are attractive. This study investigates the anti-inflammatory potential of nutritional PUFAs in an experimentally induced bronchial inflammation. METHODS: We examined 38 grass pollen allergic asthmatics and 19 controls. History of dietary PUFA intake was compared with levels of PUFAs in erythrocyte membranes, and stratified according to low (25th quartile; Q25) and high (75th quartile; Q75) ratios of omega-3 (n-3) to omega-6 (n-6) PUFAs as a surrogate for anti-inflammatory (Q75) or proinflammatory (Q25) effects. Bronchial inflammation was simulated with one-step inhalation of grass pollen. Bronchial response (exhaled nitric monoxide, eNO as surrogate for inflammation, decrease of FEV(1)) was correlated with levels of PUFAs in erythrocyte membranes. RESULTS: Ratios of n-3/n-6 PUFA were significantly lower in asthmatics than in healthy controls. Levels of eNO were significantly higher in Q25 asthmatics than in Q75 asthmatics (p = 0.040). There was a trend of higher bronchial hyperreactivity in Q25 asthmatics (median PD(20) 0.27 vs. 0.14; n.s.), induced by specific bronchial challenge with grass pollen (FEV(1) decrease 16.7 vs. 23.1%; n.s.). CONCLUSION: When stratifying for erythrocyte membrane PUFA content as a surrogate for alimentary intake, we found mild effects on bronchial allergic inflammation. Future intervention studies with pharmacological PUFA doses appear suitable to clarify dietary PUFA role as an adjunctive intervention to the established treatment of asthma. ClinicalTrials.gov No. NCT00519740.
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Ácidos Grasos Omega-3/uso terapéutico , Óxido Nítrico/metabolismo , Poaceae/inmunología , Rinitis Alérgica Estacional/terapia , Adolescente , Adulto , Pruebas de Provocación Bronquial , Bronquitis/inmunología , Bronquitis/terapia , Suplementos Dietéticos , Ácidos Grasos Omega-3/inmunología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Rinitis Alérgica Estacional/inmunología , Espirometría , Encuestas y Cuestionarios , Adulto JovenRESUMEN
OBJECTIVES: To obtain a balance in the fatty acid (FA) metabolism is important for the inflammatory response and of special importance in cystic fibrosis (CF), which is characterized by impaired FA metabolism, chronic inflammation, and infection in the airways. Nitric oxide (NO) has antimicrobial properties and low nasal (nNO) and exhaled NO (FENO), commonly reported in CF that may affect bacterial status. The present study investigates the effect of different FA blends on nNO and FENO and immunological markers in patients with CF. PATIENTS AND METHODS: Forty-three patients with CF and "severe" mutations were consecutively enrolled in a randomized double-blind placebo-controlled study with 3 FA blends containing mainly n-3 or n-6 FA or saturated FA acting as placebo. FENO, nNO, serum phospholipid concentrations of FA, and biomarkers of inflammation were measured before and after 3 months of supplementation. RESULTS: Thirty-five patients in clinically stable condition completed the study. The serum phospholipid FA pattern changed significantly in all 3 groups. An increase of the n-6 FA, arachidonic acid, was associated with a decrease of FENO and nNO. The inflammatory biomarkers, erythrocyte sedimentation rate, and interleukin-8 decreased after supplementation with n-3 FA and erythrocyte sedimentation rate increased after supplementation with n-6 FA. CONCLUSIONS: This small pilot study indicated that the composition of dietary n-3 and n-6 FA influenced the inflammatory markers in CF. FENO and nNO were influenced by changes in the arachidonic acid concentration, supporting previous studies suggesting that both the lipid abnormality and the colonization with Pseudomonas influenced NO in the airways.
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Fibrosis Quística/tratamiento farmacológico , Ácidos Grasos Omega-3/farmacología , Ácidos Grasos Omega-6/farmacología , Mediadores de Inflamación/sangre , Óxido Nítrico/metabolismo , Sistema Respiratorio/metabolismo , Adolescente , Adulto , Ácido Araquidónico/sangre , Biomarcadores/sangre , Sedimentación Sanguínea/efectos de los fármacos , Niño , Fibrosis Quística/metabolismo , Suplementos Dietéticos , Ácidos Grasos Omega-3/sangre , Ácidos Grasos Omega-3/uso terapéutico , Ácidos Grasos Omega-6/sangre , Ácidos Grasos Omega-6/uso terapéutico , Femenino , Humanos , Interleucina-8/sangre , Masculino , Mucosa Nasal/metabolismo , Fosfolípidos/sangre , Proyectos Piloto , Adulto JovenRESUMEN
Recent studies have demonstrated that n-3 polyunsaturated fatty acids such as eicosapentaenoic acid (EPA) are able to suppress cell proliferation and inhibit tumor growth. The objective of our study was to investigate the influence of a high dose EPA on the development of the tumor phenotype in ataxia-telangiectasia mutated (Atm)-deficient mice, a genetic cancer model that is associated with increased levels of oxidative stress. We analyzed toxicity, proliferation, cell-cycle progression, and apoptosis of EPA in vitro and latency to tumorigenesis in vivo. Because of the impact of reactive oxygen species (ROS) on the tumor incidence in ataxia telangiectasia (AT), we further analyzed the effect of EPA on the generation of ROS and oxidative DNA damage (ODD). EPA effectively inhibited proliferation, altered cell-cycle progression, and induced apoptosis of tumor cells (AT-4). EPA showed no effect on the latency to tumorigenesis in Atm-deficient mice. EPA treatment was accompanied by a significant increase of ROS and ODD. Our results demonstrate the antiproliferative effect of EPA on tumor cells by alteration of cell-cycle progression and induction of apoptosis in vitro. On the other hand, EPA treatment of Atm-deficient mice led to the formation of ROS and accumulation of ODD that might have abrogated the anticarcinogenic effect caused by EPA.
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Anticarcinógenos/farmacología , Proteínas de Unión al ADN/deficiencia , Ácido Eicosapentaenoico/farmacología , Proteínas Serina-Treonina Quinasas/deficiencia , Especies Reactivas de Oxígeno/metabolismo , Proteínas Supresoras de Tumor/deficiencia , Animales , Apoptosis/efectos de los fármacos , Proteínas de la Ataxia Telangiectasia Mutada , Ciclo Celular/efectos de los fármacos , Proteínas de Ciclo Celular , Proliferación Celular/efectos de los fármacos , Daño del ADN , Ácido Eicosapentaenoico/análisis , Membrana Eritrocítica/química , RatonesRESUMEN
OBJECTIVES: To compare fatty acid composition of human milk at 2 different stages of lactation and investigate the relation between trans isomeric and long-chain polyunsaturated fatty acids (LCPUFAs) in human milk at the sixth month of lactation. SUBJECTS AND METHODS: We investigated human milk samples obtained at the sixth week and sixth month of lactation from 462 mothers who participated in a large birth cohort study. Fatty acid composition of human milk lipids was determined by high-resolution capillary gas-liquid chromatography. RESULTS: Fat contents of human milk increased significantly between the sixth week and sixth month of lactation (1.63 [2.06] and 3.19 [3.14], g/100 mL; median [interquartile range], P < 0.001). Percentage contributions to human milk fatty acid composition of nearly all polyunsaturated fatty acids also increased significantly (linoleic acid: 10.09 [4.41] and 11.01 [4.53], arachidonic acid: 0.46 [0.32] and 0.48 [0.23], alpha-linolenic acid: 0.69 [0.42] and 0.75 [0.41], and docosahexaenoic acid: 0.17 [0.23] and 0.23 [0.15], % wt/wt, P < 0.001). Values of the 18-carbon trans octadecenoic acid (C18:1n-7/9t) significantly inversely correlated to linoleic acid (r = -0.24, P < 0.001), alpha-linolenic acid (r = -0.19, P < 0.001), and arachidonic acid (r = -0.43, P < 0.001). In contrast, we found no correlation between the 16-carbon trans hexadecenoic acid (C16:1n-7t) and the same LCPUFAs. CONCLUSIONS: Data obtained in the present study indicate increasing fat contents with stable or increasing percentage contribution of LCPUFAs in human milk samples between the sixth week and at the sixth month of lactation, and the availability of 18-carbon trans isomeric fatty acids is inversely associated to the availability of several LCPUFAs in human milk at the sixth month of lactation.
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Grasas/análisis , Ácidos Grasos Insaturados/análisis , Ácidos Grasos/análisis , Lactancia , Leche Humana/química , Adulto , Femenino , Humanos , Madres , Adulto JovenRESUMEN
The underlying mechanisms by which eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) affect host resistance to Pseudomonas aeruginosa are unclear. The aim of this study was to determine their role on the kinetic of pro- and antiinflammatory response in lung infection. Mice fed either a control diet or a diet enriched with EPA and DHA were infected intratracheally and we studied lung expression of proinflammatory markers [CXCL1, interleukin (IL)-6, tumor necrosis factor-alpha], antiinflammatory markers (IL-10, A20, and IkappaB alpha), and PPARalpha and PPARgamma. The inflammatory response was assessed using recruitment of neutrophils and macrophages into bronchoalveolar lavage fluid, bacterial clearance from the lung, pulmonary injury, and 7-d survival rate. Compared with the control group, EPA and DHA delayed the expression of proinflammatory markers during the first 2 h (P < 0.05), upregulated proinflammatory marker expression (P < 0.05), and induced overexpression of antiinflammatory markers at 8 h (P < 0.05), enhanced recruitment of neutrophils at 16 h (P < 0.05), and induced PPARalpha and PPARgamma overexpression at 4 and 8 h (P < 0.01), respectively. Pulmonary bacterial load decreased and pulmonary injury and mortality were reduced during the first 24 h (P < 0.05). In conclusion, EPA and DHA modulate the balance between pro- and antiinflammatory cytokines, alter the early response of the host to P. aeruginosa infection, and affect the early outcome of infection.
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Ácidos Grasos Omega-3/farmacología , Neumonía Bacteriana/metabolismo , Infecciones por Pseudomonas/metabolismo , Pseudomonas aeruginosa , Animales , Líquido del Lavado Bronquioalveolar/citología , Dieta , Perfilación de la Expresión Génica , Regulación de la Expresión Génica/efectos de los fármacos , Macrófagos/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Neurturina , Neumonía Bacteriana/microbiología , Infecciones por Pseudomonas/microbiología , TiempoRESUMEN
BACKGROUND: The intestinal mucosa functions as a barrier against harmful dietary and microbial antigens. An intact gut barrier forms a prerequisite for protection against infection and allergy. Both allergic and inflammatory mediators (e.g. IL-4, IFN-gamma) are known to compromise the epithelial barrier integrity by enhancing permeability. Breast milk provides protection against infection and allergy and contains polyunsaturated fatty acids (PUFA). AIM OF THE STUDY: Although PUFA are commonly used in infant formulas their effect on intestinal barrier is still poorly understood. Therefore the effects of distinct PUFA (n-6: LA, GLA, DGLA, AA; n-3: ALA, EPA, DHA) and a fat blend with PUFA composition similar to that of the human breast milk fat fraction, on barrier integrity were investigated. METHODS: Human intestinal epithelial cells (T84) were pre-incubated with individual PUFA or a lipase treated fat blend, with or without subsequent IL-4 exposure. Barrier integrity was evaluated by measuring transepithelial resistance and permeability. Membrane phospholipid composition was determined by capillary gas chromatography. RESULTS: DGLA, AA, EPA, DHA and to a lesser extend GLA enhanced basal TER and strongly reduced IL-4 mediated permeability, while LA and ALA were ineffective. Furthermore, the lipase treated fat blend effectively supported barrier function. PUFA were incorporated in the membrane phospholipid fraction of T84 cells. CONCLUSIONS: Long chain PUFA DGLA, AA, EPA and DHA were particularly effective in supporting barrier integrity by improving resistance and reducing IL-4 mediated permeability. Fat blends that release specific PUFA upon digestion in the gastrointestinal tract may support natural resistance.
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Grasas Insaturadas en la Dieta/farmacología , Ácidos Grasos Insaturados/farmacología , Inmunidad Mucosa/efectos de los fármacos , Interleucina-4/metabolismo , Mucosa Intestinal/fisiología , Permeabilidad/efectos de los fármacos , Células Cultivadas , Cromatografía de Gases , Grasas Insaturadas en la Dieta/metabolismo , Sinergismo Farmacológico , Células Epiteliales , Ácidos Grasos Omega-3/farmacología , Ácidos Grasos Omega-6/farmacología , Ácidos Grasos Insaturados/metabolismo , Hipersensibilidad a los Alimentos/inmunología , Hipersensibilidad a los Alimentos/prevención & control , Humanos , Inmunidad Mucosa/fisiología , Interleucina-4/inmunología , Mucosa Intestinal/inmunología , Mucosa Intestinal/microbiología , Leche Humana/química , Leche Humana/inmunologíaRESUMEN
BACKGROUND: Galactooligosaccharides (GOS) and long-chain fructooligosaccharides (lcFOS) proliferate bifidobacteria in infant gut microbiota. However, it is not known how GOS and FOS influence the microbiota of pregnant women and whether a potential prebiotic effect is transferred to the offspring. OBJECTIVES: We aimed to test how supplementation with GOS and lcFOS (GOS/lcFOS) in the last trimester of pregnancy affects maternal and neonatal gut microbiota. Variables of fetal immunity were assessed as a secondary outcome. DESIGN: In a randomized, double-blind, placebo-controlled pilot study, 48 pregnant women were supplemented 3 times/d with 3 g GOS/lcFOS (at a ratio of 9:1) or maltodextrin (placebo) from week 25 of gestation until delivery. Percentages of bifidobacteria and lactobacilli within total bacterial counts were detected by fluorescent in situ hybridization and quantitative polymerase chain reaction in maternal and neonatal (days 5, 20, and approximately 182) stool samples. Variables of fetal immunity were assessed in cord blood by using flow cytometry and cytokine multiplex-array analysis. RESULTS: The proportions of bifidobacteria in the maternal gut were significantly higher in the supplemented group than in the placebo group (21.0% and 12.4%, respectively; P = 0.026); the proportion of lactobacilli did not differ between the groups. In neonates, bifidobacteria and lactobacilli percentages, diversity and similarity indexes, and fetal immune parameters did not differ significantly between the 2 groups. Mother-neonate similarity indexes of bifidobacteria decreased over time. CONCLUSIONS: GOS/lcFOS supplementation has a bifidogenic effect on maternal gut microbiota that is not transferred to neonates. The increased maternal bifidobacteria did not affect fetal immunity as measured by a comprehensive examination of cord blood immunity variables.
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Suplementos Dietéticos , Feto/inmunología , Intestinos/microbiología , Oligosacáridos/administración & dosificación , Probióticos/administración & dosificación , Trisacáridos/administración & dosificación , Adolescente , Adulto , Bifidobacterium , Citocinas/biosíntesis , Método Doble Ciego , Femenino , Fructosa/administración & dosificación , Humanos , Recién Nacido , Persona de Mediana Edad , Embarazo , Subgrupos de Linfocitos T/inmunologíaRESUMEN
OBJECTIVE: The aim of the present study was to examine the immune-modulating effect of two different fat blends enriched with a low dose of anti- or proinflammatory polyunsaturated fatty acids on the fatty acid status and subsequently on the immune response of healthy volunteers. METHODS: Thirty healthy volunteers were randomly assigned to group A (anti-inflammatory blend rich in polyunsaturated fatty acids: alpha-linolenic acid, 240 mg/d; eicosapentaenoic acid, 120 mg/d; stearidonic acid, 49 mg/d; and gamma-linolenic acid, 73 mg/d) or group B (arachidonic acid, 40 mg/d; containing an inflammatory fat blend) for a 2-wk dietary supplementation period. Concentrations of interleukin-8, interleukin-10, tumor necrosis factor-alpha, prostaglandins E(1) and E(2), and leukotriene B(4) were investigated before, after 2 wk of supplementation, and 2 wk after stopping supplementation using a whole blood ex vivo lipopolysaccharide-stimulation assay. RESULTS: Plasma concentrations of alpha-linolenic acid and eicosapentaenoic acid were significantly increased in group A. In addition, dietary fat blends influenced eicosapentaenoic acid concentration in erythrocyte membranes. Supplementation of the fat blends resulted in contrasting effects on the expression of lipid mediators and cytokines after ex vivo lipopolysaccharide stimulation. Release of prostaglandin E(1) and leukotriene B(4) were significantly decreased in group A, whereas prostaglandin E(2) and interleukin-10 concentrations were significantly increased in group B. No effect on interleukin-8 or tumor necrosis factor-alpha release was found after supplementation with either fat blend. CONCLUSIONS: These results show an immune-modulating effect of a low-dose dietary polyunsaturated fatty acid supplementation. However, further studies regarding fat-blend composition and period of supplementation in patients with inflammatory conditions are required.
Asunto(s)
Ácidos Eicosanoicos/sangre , Ácidos Grasos Insaturados/sangre , Ácidos Grasos Insaturados/farmacología , Inflamación/sangre , Ácido alfa-Linolénico/sangre , Alprostadil/sangre , Suplementos Dietéticos , Dinoprostona/sangre , Método Doble Ciego , Membrana Eritrocítica/química , Ácidos Grasos Omega-3/administración & dosificación , Ácidos Grasos Omega-3/sangre , Ácidos Grasos Omega-3/farmacología , Ácidos Grasos Omega-6/administración & dosificación , Ácidos Grasos Omega-6/sangre , Ácidos Grasos Omega-6/farmacología , Ácidos Grasos Insaturados/administración & dosificación , Femenino , Humanos , Interleucina-10/sangre , Interleucina-8/sangre , Leucotrieno B4 , Masculino , Factores de Tiempo , Factor de Necrosis Tumoral alfa/sangreRESUMEN
BACKGROUND: Mucin hypersecretion and mucus plugging in the airways are characteristic features of chronic respiratory diseases like cystic fibrosis (CF) and contribute to morbidity and mortality. In CF, Pseudomonas aeruginosa superinfections in the lung exacerbate inflammation and alter mucus properties. There is increasing evidence that n-3 polyunsaturated fatty acids (PUFAs) exhibit anti-inflammatory properties in many inflammatory diseases while n-6 PUFA arachidonic acid (AA) favors inflammatory mediators such as eicosanoids prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) that may enhance inflammatory reactions. This suggests that n-3 PUFAs may have a protective effect against mucus over-production in airway diseases. Therefore, we hypothesized that n-3 PUFAs may downregulate mucins expression. METHODS: We designed an absolute real-time PCR assay to assess the effect of a 5-week diet enriched either with n-3 or n-6 PUFAs on the expression of large mucins in the lungs of mice infected by P. aeruginosa. RESULTS: Dietary fatty acids did not influence mucin gene expression in healthy mice. Lung infection induced an increase of the secreted gel-forming mucin Muc5b and a decrease of the membrane bound mucin Muc4. These deregulations are modulated by dietary fatty acids with a suppressive effect of n-3 PUFAs on mucin (increase of Muc5b from 19-fold up to 3.6 x 10(5)-fold for the n-3 PUFAs treated group and the control groups, respectively, 4 days post-infection and decrease of Muc4 from 15-fold up to 3.2 x 10(4)-fold for the control and the n-3 PUFAs treated groups, respectively, 4 days post-infection). CONCLUSION: Our data suggest that n-3 PUFAs enriched diet represents an inexpensive strategy to prevent or treat mucin overproduction in pulmonary bacterial colonization.
Asunto(s)
Ácidos Grasos Omega-3/administración & dosificación , Pulmón/efectos de los fármacos , Pulmón/metabolismo , Mucinas/metabolismo , Infecciones por Pseudomonas/metabolismo , Administración Oral , Animales , Masculino , Ratones , Ratones Endogámicos C57BL , Infecciones por Pseudomonas/dietoterapia , Resultado del Tratamiento , Regulación hacia Arriba/efectos de los fármacosRESUMEN
BACKGROUND: Several observational studies indicate that trans isomeric fatty acids may interfere with the metabolism of essential fatty acids in the human organism. OBJECTIVE: The objective was to investigate the relation between trans fatty acids and long-chain polyunsaturates in mature human milk. DESIGN: Human milk samples (n=769) were obtained at the 6th week of lactation from mothers participating in a birth cohort study in Germany. The fatty acid composition of the milk samples was measured by high-resolution capillary gas-liquid chromatography. RESULTS: trans Octadecenoic and trans octadecadienoic acids were inversely correlated with linoleic acid (r=-0.32 and -0.33, P<0.0001 for both), alpha-linolenic acid (r=-0.35 and -0.27, P<0.0001), arachidonic acid (r=-0.60 and -0.47, P<0.0001), and docosahexaenoic acid (r=-0.51 and -0.33, P<0.0001). In contrast, no inverse correlations were observed between trans hexadecenoic acid and polyunsaturated fatty acids. CONCLUSIONS: The data obtained in the present study suggest that the availability of 18-carbon trans isomeric fatty acids may be inversely related to the availability of long-chain polyunsaturated fatty acids in mature human milk.
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Ácidos Grasos Insaturados/análisis , Leche Humana/química , Ácidos Esteáricos/análisis , Ácidos Grasos trans/análisis , Adulto , Cromatografía de Gases/métodos , Estudios de Cohortes , Ácidos Grasos Esenciales/análisis , Ácidos Grasos Esenciales/química , Ácidos Grasos Omega-3/análisis , Ácidos Grasos Omega-6/análisis , Ácidos Grasos Insaturados/química , Femenino , Alemania , Humanos , Isomerismo , Ácidos Linolénicos/análisis , Periodo Posparto , Ácidos Esteáricos/química , Ácidos Grasos trans/química , Ácido alfa-Linolénico/análisisRESUMEN
The sn position of fatty acids in seed oil lipids affects physiological function in pharmaceutical and dietary applications. In this study the composition of acyl-chain substituents in the sn positions of glycerol backbones in triacylglycerols (TAG) have been compared. TAG from native and transgenic medium-chain fatty acid-enriched rape seed oil were analyzed by reversed-phase high performance liquid chromatography coupled with online atmospheric-pressure chemical ionization ion-trap mass spectrometry. The transformation of summer rape with thioesterase and 3-ketoacyl-[ACP]-synthase genes of Cuphea lanceolata led to increased expression of 1.5% (w/w) caprylic acid (8:0), 6.7% (w/w) capric acid (10:0), 0.9% (w/w) lauric acid (12:0), and 0.2% (w/w) myristic acid (14:0). In contrast, linoleic (18:2n6) and alpha-linolenic acid (18:3n3) levels decreased compared with the original seed oil. The TAG sn position distribution of fatty acids was also modified. The original oil included eleven unique TAG species whereas the transgenic oil contained sixty. Twenty species were common to both oils. The transgenic oil included trioctadecenoyl-glycerol (18:1/18:1/18:1) and trioctadecatrienoyl-glycerol (18:3/18:3/18:3) whereas the native oil included only the latter. The transgenic TAG were dominated by combinations of caprylic, capric, lauric, myrisitic, palmitic (16:0), stearic (18:0), oleic (18:1n9), linoleic, arachidic (20:0), behenic (22:0), and lignoceric acids (24:0), which accounted for 52% of the total fat. In the original TAG palmitic, stearic, oleic, and linoleic acids accounted for 50% of the total fat. Medium-chain triacylglycerols with capric and lauric acids combined with stearic, oleic, linoleic, alpha-linolenic, arachidic, and gondoic acids (20:1n9) accounted for 25% of the transgenic oil. The medium-chain fatty acids were mainly integrated into the sn-1/3 position combined with the essential linoleic and alpha-linolenic acids at the sn-2 position. Eight species contained caprylic, capric, and lauric acids in the sn-2 position. The appearance of new TAG in the transgenic oil illustrates the extensive effect of genetic modification on fat metabolism by transformed plants and offers interesting possibilities for improved enteral applications.
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Cromatografía Liquida/métodos , Espectrometría de Masas/métodos , Aceites de Plantas/química , Plantas Modificadas Genéticamente/química , Triglicéridos/análisis , Presión Atmosférica , Cromatografía Líquida de Alta Presión , Ácidos Grasos Monoinsaturados , Aceite de Brassica napus , Triglicéridos/químicaRESUMEN
Pseudomonas aeruginosa is a gram-negative bacilli frequently encountered in human pathology. This pathogen is involved in a large number of nosocomial infections and chronic diseases. Herein we investigated the effects of polyunsaturated fatty acids (PUFA) in chronic Pseudomonas aeruginosa lung infection. C57BL/6 mice were fed for 5 wk with specifically designed diets with high contents in either omega-3 (omega-3) or omega-6 PUFA and compared to a control diet. P. aeruginosa included in agarose beads was then instilled intratracheally, and the animals were studied for 7 days. On the 4th day, the mice fed with the omega-3 diet had a higher lean body mass gain and a lower omega-6:omega-3 ratio of fatty acids extracted from the lung tissue compared with the other groups (P < 0.05). The omega-3 group had the lowest mortality. Distal alveolar fluid clearance (DAFC) as well as the inflammatory response and the cellular recruitment were higher in the omega-3 group on the 4th day. The effect on DAFC was independent of alpha-epithelial Na(+) channels (alpha-ENaC), beta-ENaC, and alpha(1)-Na-K-ATPase mRNA expressions, which were not altered by the different diets. In conclusion, a diet enriched in omega-3 PUFA can change lung membrane composition and improve survival in chronic pneumonia. This effect on survival is probably multifactorial involving the increased DAFC capacity as well as the optimization of the initial inflammatory response. This work suggests that a better control of the omega-6/omega-3 PUFA balance may represent an interesting target in the prevention and/or control of P. aeruginosa infection in patients.
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Ácidos Grasos Omega-3/farmacología , Neumonía Bacteriana/tratamiento farmacológico , Infecciones por Pseudomonas/tratamiento farmacológico , Pseudomonas aeruginosa , Alimentación Animal , Animales , Líquido del Lavado Bronquioalveolar/inmunología , Canales Epiteliales de Sodio/genética , Agua Pulmonar Extravascular/metabolismo , Interleucina-6/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Neutrófilos/inmunología , Neumonía Bacteriana/inmunología , Infecciones por Pseudomonas/inmunología , Alveolos Pulmonares/metabolismo , Alveolos Pulmonares/microbiología , ARN Mensajero/metabolismo , ATPasa Intercambiadora de Sodio-Potasio/genética , Factor de Necrosis Tumoral alfa/metabolismo , Pérdida de PesoRESUMEN
BACKGROUND: The presence of the adipokines adiponectin and leptin in cord blood and placental and fetal tissues suggests a possible role in fetal development. METHODS: We measured concentrations of adiponectin and leptin in maternal serum, cord blood, and breast milk and examined their correlations within a large, population-based study. Between November 2000 and November 2001, we recruited all mothers and their newborns after delivery at the University of Ulm (Ulm, Germany). The current analysis included 766 mothers with available breast milk samples collected 6 weeks postpartum. Adipokine concentrations were measured with commercially available ELISAs (R&D Systems). RESULTS: Median adiponectin concentrations in maternal serum (n=713), cord blood (n=709), and breast milk (n=766) were 8.6 mg/L, 30.6 mg/L, and 10.9 microg/L, respectively. Median leptin concentrations were 12.8 microg/L in maternal serum, 7.8 microg/L in cord blood, and 174.5 ng/L in breast milk. Whereas increases in leptin concentrations with increasing birth weight, birth weight according to gestational age, and ponderal index were statistically significant in cord blood (all P values<0.0001), cord blood adiponectin was clearly related only to birth weight (P=0.0004). Concentrations of both adipokines were moderately correlated in breast milk and maternal serum (both Spearman rho values were 0.43; P<0.0001). CONCLUSIONS: Concentrations of adiponectin and leptin vary strongly in maternal serum, cord blood, and breast milk, with only moderate correlations between both adipokines in maternal serum and breast milk. The health implications of these patterns warrant further investigation.