La chía en estrategias inmunonutricionales

Recientes estudios comienzan a mostrar que los factores inmunonutricionales y su influencia e interacción con la microbiota intestinal y finalmente su diafonía con el sistema inmunológico del huésped son determinantes importantes de la salud del eje intestinal, las células iniciadoras de metástasis y la promoción del cáncer. Por ejemplo, moléculas de superficie celular multiestructurales y multifuncionales tales como el receptor de ácido grasos CD36 se han asociado directamente a metástasis y crecimiento tumoral. Además, los agonistas del sistema inmune innato, en particular, del receptor tipo Toll (TLR) -4 se han identificado como factores críticos en la promoción del carcinoma hepatocelular e incluso modulan el bloqueo de control mediado por inmunidad. La respuesta molecular derivada de TLR4 puede ser dirigida por nutrientes, inmunológicamente activos, modulando la plasticidad de ambas respuestas inmunes; innata y adaptativa. En este contexto, la nutrición personalizada de precisión puede tener un gran impacto en la salud para reducir el riesgo de enfermedades metabólicas e inmunológicas y, particularmente, aquellas asociadas a la promoción y/o progresión del cáncer. Hasta la fecha, el interés principal de la investigación se ha centrado en la influencia de pre/probióticos. Sin embargo, todavía quedan preguntas clave sin respuesta sobre los factores inmunonutricionales que en general requieren un esfuerzo concertado para superar el enfoque normalmente fragmentado y compartimentado para abordar su impacto

Industrial By-Products As a Novel Circular Source of Biocompatible Extracellular Vesicles

Extracellular vesicles (EVs) constitute an intricate system of molecular exchange that has recently gained tremendous interest. However, sustainable sources of safe biological EVs remain scarce and elusive. This study explores and defines the use of food industry by-products (BP) as a circular source of safe biocompatible EVs. Averaged diameter and molecular compositions indicate a large yield of exosomes and high abundancy of membrane lipids with signaling capacity in these vesicles. Complex proteomes mimicking those circulating in human blood plasma are also identified. Furthermore, BP-EVs do not show relevant cytotoxicity and display excellent oral and intravenous bioavailability together with specific organ targeting capacity. Collectively, it is believed that the novel findings reported here will open substantial venues for the use of BP as an optimal source of biocompatible nanovesicles in manifold applications of the biotechnological and biomedical fields.The authors sincerely thank Gemma Plaza, oenologist at the Castell del Remei winery in Penelles, Lleida, Spain and Juan Carlos Blanco, production manager at Mahou San Miguel in Alovera, Madrid, Spain for their kind and altruistic help on the obtention of their respective industry by-product samples. The authors also thank Dr. Hector Peinado and his research group at the National Center for Oncology Research (CNIO) in Madrid (Spain) for their support on the morphometric characterization of BP-EVs. Support for this work was provided by the Research and Education Council of the Community of Madrid, Spain (2018-T1/ BIO-10633), Ministry of Science and Innovation, Spain (PID2020- 114885RB-C21) and a FIS project by Carlos III Institute of Health (ISCIII), Spain (PI20/00623). A.S. acknowledges a grant from the Talento Program 2018 of the Community of Madrid. X.G.-P. acknowledges grants from Sara Borrell postdoctoral program (CD19/00243) and Miguel Servet tenure track program (CP21/00096) of the Instituto de Salud Carlos III (ISCIII, Spain), respectively awarded on the 2019 and 2021 calls under ISCIII-Health Strategy Actions [These grants are cofunded with European Union Funds (ISCIII Miguel Servet Program 2021 is cofunded by Fondo Social Europeo Plus, FSE+)]. M.V.C. acknowledges a Miguel Servet program contract (CPII20/00007). C.L.’s Ph.D. was funded by the Regional Ministry of Science, Universities and Innovation of the Community of Madrid and the European Social Fund for the recruitment of predoctoral researchers (PEJD-2019-PRE/BIO-16475). IRBLLEIDA and X.G.-P. are co-funded by CERCA Program/Generalitat de Catalunya

Almond milk fermented with different potentially probiotic bacteria improves iron uptake by intestinal epithelial (Caco-2) cells

Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal[EN] New fermented almond milks were developed by using different potentially probiotic bacteria in order to cover the current demand for health-versatile non-dairy products. An in vitro digestion/Caco-2 cell model was used to evaluate the effect of both non-fermented and fermented almond milks on the mitochondrial enzymatic activities of enterocytes. Moreover, macrophages were challenged with the in-vitro digested samples and the production of pro-inflammatory biomarkers TNF- Ñ and IL-6 was quantified. Enzymatic activities of cell cultures seemed to be stimulated by the exposure to both fermented and non-fermented almond milks. Both biomarkers decreased (p< 0.05) in fermented almond milks with either B. bifidum or B. longum. Results showed that fermented almond products favored the energetic metabolism of enterocytes and had a lower inflammatory response than initial almond milk, suggesting it is beneficial for the management of allergies/intolerances. Moreover, the fermentation process enhanced the uptake of iron by Caco-2 cells, especially when using L. rhamnosus and either B. bifidum or B. longum as starters, thus improving the product bioactivity. Therefore, new non-dairy fermented products with functional properties were developed, which might be highly potential alternatives to cow-milk products for sensitized groups of population (allergic and/or intolerant to cow milk or anemic population, among others).This research has been carried out thanks to a funded project by the Universitat Politècnica de València (PAID-05-11-2740). This work was also supported by the Conselleria de Educación of Valencia government, which granted the author N. Bernat (ACIF/2011).Bernat Pérez, N.; Cháfer Nácher, MT.; Chiralt, A.; Laparra Llopis, JM.; González Martínez, MC. (2015). Almond milk fermented with different potentially probiotic bacteria improves iron uptake by intestinal epithelial (Caco-2) cells. International Journal of Food Studies. 4:49-60. https://doi.org/10.7455/ijfs/4.1.2015.a4S4960

Phenolic diterpenes from Rosemary supercritical extract inhibit non-small cell lung cancer lipid metabolism and synergise with therapeutic drugs in the clinic

Lung cancer is one of the most deadly and common cancers in the world. The molecular features of patient’s tumours dictate the different therapeutic decisions, which combines targeted therapy, chemotherapy, and immunotherapy. Altered cellular metabolism is one of the hallmarks of cancer. Tumour cells reprogram their metabolism to adapt to their novel requirements of growth, proliferation, and survival. Together with the Warburg effect, the role of lipid metabolism alterations in cancer development and prognosis has been highlighted. Several lipid related genes have been shown to promote transformation and progression of cancer cells and have been proposed as biomarkers for prognosis. Nevertheless, the exact mechanisms of the regulation of lipid metabolism and the biological consequences in non-small cell lung cancer (NSCLC) have not been elucidated yet. There is an urgent necessity to develop multidisciplinary and complementary strategies to improve NSCLC patients´ well-being and treatment response. Nutrients can directly affect fundamental cellular processes and some diet-derived ingredients, bioactive natural compounds and natural extracts have been shown to inhibit the tumour growth in preclinical and clinical trials. Previously, we described a supercritical extract of rosemary (SFRE) (12 - 16% composition of phenolic diterpenes carnosic acid and carnosol) as a potential antitumoral agent in colon and breast cancer due to its effects on the inhibition of lipid metabolism and DNA synthesis, and in the reduction of resistance to 5-FluoroUracil (5-FU). Herein, we demonstrate SFRE inhibits NSCLC cell bioenergetics identifying several lipid metabolism implicated targets. Moreover, SFRE synergises with standard therapeutic drugs used in the clinic, such as cisplatin, pemetrexed and pembrolizumab to inhibit of cell viability of NSCLC cells. Importantly, the clinical relevance of SFRE as a complement in the treatment of NSCLC patients is suggested based on the results of a pilot clinical trial where SFRE formulated with bioactive lipids (PCT/ES2017/070263) diminishes metabolic and inflammatory targets in peripheral-blood mononuclear cells (PBMC), such as MAPK (p=0.04), NLRP3 (p=0.044), and SREBF1 (p=0.047), which may augment the immune antitumour function. Based on these results, SFRE merits further investigation as a co-adjuvant in the treatment of NSCLC.This research was funded by Regional Government of Community of Madrid (IND2017/BIO-7857; P2018/BAA-4343-ALIBIRD2020-CM), Ministerio de Ciencia e Innovación, Spain (PID2019-110183RB-C21); Ramon Areces Foundation (CIVP19A5937); EU Structural Funds and COST Action (CA17118); Synergistic Projects Community of Madrid (NUTRISION-CM/Y2020/BIO-6350) and REACT EU Program (Comunidad de Madrid and The European Regional Development Fund. ERDF. European Union- FACINGLCOVID-CM project). Adrián Bouzas has a predoctoral grant from the industrial predoctoral program of Community of Madrid (IND2017/BIO-7857).Peer reviewe

Bifidobacterium longum CECT 7347 Modulates Immune Responses in a Gliadin-Induced Enteropathy Animal Model

Coeliac disease (CD) is an autoimmune disorder triggered by gluten proteins (gliadin) that involves innate and adaptive immunity. In this study, we hypothesise that the administration of Bifidobacterium longum CECT 7347, previously selected for reducing gliadin immunotoxic effects in vitro, could exert protective effects in an animal model of gliadin-induced enteropathy. The effects of this bacterium were evaluated in newborn rats fed gliadin alone or sensitised with interferon (IFN)-γ and fed gliadin. Jejunal tissue sections were collected for histological, NFκB mRNA expression and cytokine production analyses. Leukocyte populations and T-cell subsets were analysed in peripheral blood samples. The possible translocation of the bacterium to different organs was determined by plate counting and the composition of the colonic microbiota was quantified by real-time PCR. Feeding gliadin alone reduced enterocyte height and peripheral CD4+ cells, but increased CD4+/Foxp3+ T and CD8+ cells, while the simultaneous administration of B. longum CECT 7347 exerted opposite effects. Animals sensitised with IFN-γ and fed gliadin showed high cellular infiltration, reduced villi width and enterocyte height. Sensitised animals also exhibited increased NFκB mRNA expression and TNF-α production in tissue sections. B. longum CECT 7347 administration increased NFκB expression and IL-10, but reduced TNF-α, production in the enteropathy model. In sensitised gliadin-fed animals, CD4+, CD4+/Foxp3+ and CD8+ T cells increased, whereas the administration of B. longum CECT 7347 reduced CD4+ and CD4+/Foxp3+ cell populations and increased CD8+ T cell populations. The bifidobacterial strain administered represented between 75–95% of the total bifidobacteria isolated from all treated groups, and translocation to organs was not detected. These findings indicate that B. longum attenuates the production of inflammatory cytokines and the CD4+ T-cell mediated immune response in an animal model of gliadin-induced enteropathy

Inclusion of ancient Latin-American crops in bread formulation improves intestinal iron absorption and modulates inflammatory markers

This study compares iron (Fe) absorption in Fe-deficient animals from bread formulations prepared by substitution of white wheat flour (WB) by whole wheat flour (WWB), amaranth flour (Amaranthus hypochondriacus, 25%) (AB) and quinoa flour (Chenopodium quinoa, 25%) (QB), or chia flour (Salvia hispanica L, 5%) (ChB). Hematological parameters of Fe homeostasis, plasmatic active hepcidin peptide production (LC coupled to Ms/Ms), and liver TfR-2 and IL-6 expression (RT-qPCR) were determined. The different bread formulations increased Fe content between 14% and 83% relative to white bread. Only animals fed with WWB, AB and ChB increased haemoglobin concentrations significantly. Feeding the different bread formulations did not increase hepcidin levels, but down-regulated transferrin receptor 2 (TfR2) (apart from WWB) and IL-6 (apart from QB) expression levels. Only AB and ChB had a significant influence on Fe bioavailability at the investigated level of substitution. The potential contribution of these flours would not differ considerably from that of WWB.This work was financially supported by grants I-Link0923 from the Ministry of Economy and Competitiveness (MINECO) and PROMETEO/2012/064 from the Generalitat Valenciana, Spain.Peer reviewe

Interactions of gut microbiota with functional food components and nutraceuticals

7 pages, 1 table, 1 figure.-- Online version published 13 November 2009The human gut is populated by an array of bacterial species, which develop important metabolic and immune functions, with a marked effect on the nutritional and health status of the host. Dietary component also play beneficial roles beyond basic nutrition, leading to the development of the functional food concept and nutraceuticals. Prebiotics, polyunsaturated fatty acids (PUFAs) and phytochemicals are the most well characterized dietary bioactive compounds. The beneficial effects of prebiotics mainly relay on their influence on the gut microbiota composition and their ability to generate fermentation products (short-chain fatty acids) with diverse biological roles. PUFAs include the ω-3 and ω-6 fatty acids, whose balance may influence diverse aspects of immunity and metabolism. Moreover, interactions between PUFAs and components of the gut microbiota may also influence their biological roles. Phytochemicals are bioactive non-nutrient plant compounds, which have raised interest because of their potential effects as antioxidants, antiestrogenics, anti-inflammatory, immunomodulatory, and anticarcinogenics. However, the bioavailability and effects of polyphenols greatly depend on their transformation by components of the gut microbiota. Phytochemicals and their metabolic products may also inhibit pathogenic bacteria while stimulate the growth of beneficial bacteria, exerting prebiotic-like effects. Therefore, the intestinal microbiota is both a target for nutritional intervention and a factor influencing the biological activity of other food compounds acquired orally. This review focuses on the reciprocal interactions between the gut microbiota and functional food components, and the consequences of these interactions on human health.This work was supported by grants AGL2008-01440/ALI and Consolider Fun-C-Food CSD2007-00063 from the Spanish Ministry of Science and Innovation (MICINN, Spain) and PIF08-010-4 form CSIC. J.M. Laparra has a postdoctoral contract of the programme “Juan de la Cierva” (MICINN, Spain).Peer reviewe

Comparison of in vitro models to study bacterial adhesion to the intestinal epithelium

7 pags, 1 table.-- Printed version published December 2009.-- The definitive version is available at www3.interscience.wiley.com[Aims]: To evaluate the adhesion ability of intestinal bacteria to different in vitro models of intestinal epithelia, and to estimate the suitability of these models and the type of interactions involved.[Methods and results]: The adhesion of probiotic (Lactobacillus rhamnosus GG and Bifidobacterium animalis subsp. lactis Bb12), commensal (B. animalis IATA-A2 and B. bifidum IATA-ES2) and potentially pathogenic bacteria (E. coli and L. monocytogenes) was determined. The adhesion models used were polycarbonate-well plates, with or without mucin, and different configurations of Caco-2 and/or HT29-MTX cell cultures. All bacteria adhered to wells without mucin (2·6–27·3%), the values being highly variable depending on the bacterial strain. Adhesion percentages of potentially probiotic bacteria to Caco-2 cultures were remarkably lower (P < 0·05) than those to mucin, and more similar to those of pathogenic strains. The lowest adhesion of different bacterial strains was detected on HT29-MTX (0·5–2·3%) cultures and Caco-2/HT29-MTX (0·6–3·2%) cocultures, while these values were increased in Caco-2 cultures plus mucin.[Conclusions]: The results suggested that bacterial strains exhibit different capacities to adhere to cellular components and several types of mucin present in different models, showing preferences for intestinal MUC2.[Significance and impact of the study]: The use of Caco-2 cells monolayer plus mucin (type II) better approaches the physiological characteristics of in vivo situation, providing a reliable and suitable in vitro model to evaluate bacterial adhesion.This work was supported by grants PIF08-010-4 form CSIC and Consolider Fun-C-Food CSD2007-00063 from the Spanish Ministry of Science and Innovation (Spain) for which the authors are greatly indebted. Dr José Moisés Laparra was sponsored as a researcher within the programme ‘Juan de la Cierva’ (Spain). HI29-MTX cell cultures were kindly supplied by Dr Thécla Lesufflew (INSERM U843, Paris, France).Peer reviewe

Chenopodium quinoa to Modulate Innate Myeloid Cells in the Induction of Obesity

Complex interactions between innate and adaptive immune effectors are an important component in the induction of obesity. Particularly, different subsets of myeloid cells play key roles in metabolic liver diseases and, therefore, are promising targets for intervention strategies. Chenopodium quinoa seeds constitute a good source of immunonutritional compounds, which help prevent high-fat, diet-enhanced innate immune signaling via TLR4/MyD88 that boosts inflammation. Herein, two metabolic mouse models&mdash;wild type (WT) and tributyltin treated (TBT)&mdash;were used to examine the effects associated with non-alcoholic fatty liver disease (NAFLD); mice were fed with a high-fat diet (HFD) and administered with wheat or C. quinoa bread. Variations in myeloid cells were obtained from a hemogram analysis, and rt-qPCR (mRNA) served to evaluate macrophage markers (i.e., CD68/CD206 ratio) as well as liver inflammation (i.e., Lyve-1) to gain insights into their selective functional differentiation into metabolically injured livers. Only administration of C. quinoa bread prevented alterations in the liver/body weight ratio either in WT animals or those treated with TBT. These effects were associated with significantly increased variations in the peripheral myeloid cell population. Hepatic mRNA markers revealed that C. quinoa enables a selective functional differentiation and function of intrahepatic monocyte-derived macrophages preserving tissue integrity and function

Impact of ¿-Amylase During Breadmaking on In Vitro Kinetics of Starch Hydrolysis and Glycaemic Index of Enriched Bread with Bran

Nowadays, the use of enzymes has become a common practice in the bakery industry, as they can improve dough quality and texture of final product. However, the use of α-amylases could have a negative effect in the glycaemic load of product, due to the released sugars from the starch hydrolysis that are not used by yeasts during the fermentation process. This study evaluated the effect of the addition of α-amylase in bakery products with bran on in vitro kinetics of starch hydrolysis. The use of flour with a high degree of extraction or high bran amount could decrease the GI even with the inclusion of α-amylase in the formulation. It should be taken into account the amount of bran and α-amylase when formulating breads in order to obtain products with lower GI than white bread. However, the fact that kinetics of starch hydrolysis remained unaltered indicates that the use of α-amylase in bread-making processes could provide technological advantages improving quality of breads without markedly changes in their glycaemic index.This work was financially supported by grants Consolider Fun-C-Food CSD2007-00063 from the Ministry of Economy and Competitiveness (MINECO) and PROMETEO/2012/064 from the Generalitat Valenciana, Spain. The contract of J.M. Sanz-Penella from MINECO is greatly acknowledged.Peer Reviewe