Etxeberria, U. (Usune)
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- Gut microbiota and metabolomic changes associated to the beneficial effects of polyphenols on obesity(2019-11-21) Etxeberria, U. (Usune); Martinez, J.A. (José Alfredo); Milagro-Yoldi, F.I. (Fermín Ignacio)The contribution of the gut microbiota to the development of a large number of diseases, including obesity, is being explored. Although mechanisms are not fully understood, perturbations on gut microbiota composition seem to be an important factor. Therefore, modulation of gut bacterial community with approaches (i.e. supplementation with polyphenols) that could enhance the growth of ¿friendly¿ bacteria and reduce harmful bacteria might be an effective therapeutic tool. This thesis aimed to provide a snapshot of the complex system consisting of gut microbiota, diet and polyphenols, host metabolism and health. For this purpose, this work has taken advantage of advanced technologies namely next-generation sequencing and untargeted metabolomics In the present work it is demonstrated that consumption of a high-fat high-sucrose diet strongly affects host metabolome altering serum levels of a different set of metabolites, which might be reflective of the physiopathology of diet-induced obesity. Moreover, the obesogenic diet strongly impacts gut microbiota composition perturbing the bacterial balance towards an obesity-associated gut microbial pattern. Remarkably, the use of pure natural compounds, particularly quercetin, could counteract the disturbance of gut microbiota related to diet-induced obesity. In contrast, trans-resveratrol significantly influences gene expression level in the intestine in vivo, without notably modifying gut microbial profile. In this context, trans-resveratrol seems to favour intestinal epithelial homeostasis promoting the repair of intestinal epithelial barrier, upon damage. Furthermore, from the in vitro studies conducted in Caco-2 cells, the inhibitory action of the stilbene on genes implicated in lipid metabolism has been observed. Finally, biological outcomes exerted by polyphenols on global host metabolome might be distinguished through a faecal non-targeted metabolomic analysis, proposing the potential of this technique to elucidate interactions between gut bacteria and polyphenols, and also to discriminate individuals in different groups based on the dietary intervention they have been subjected to.
- Impact of polyphenols and polyphenol-rich dietary sources on gut microbiota composition(American Chemical Society, 2013) Martinez, J.A. (José Alfredo); Etxeberria, U. (Usune); Milagro-Yoldi, F.I. (Fermín Ignacio); Portillo, M.P. (María P.); Aguirre, L. (Leixuri); Fernandez-Quintela, A. (Alfredo)Gut microbiota plays a key role in host physiology and metabolism. Indeed, the relevance of a well-balanced gut microbiota composition to an individual´s health status is essential for the person's well-being. Currently, investigations are focused on analyzing the effects of pre- and probiotics as new therapeutic tools to counteract the disruption of intestinal bacterial balance occurring in several diseases. Polyphenols exert a wide range of beneficial health effects. However, although specific attention has been paid in recent years to the function of this “biological entity” in the metabolism of polyphenols, less is known about the modulatory capacity of these bioactive compounds on gut microbiota composition. This review provides an overview of the latest investigations carried out with pure polyphenols, extracts rich in polyphenols and polyphenol-rich dietary sources (such as cocoa, tea, wine, soy products and fruits), and critically discusses the consequences to gut microbiota composition which are produced.
- Correlation between serum advanced glycation end products and dietary intake of advanced glycation end products estimated from home cooking and food frequency questionnaires(Elsevier, 2023) Etxeberria, U. (Usune); Goñi-Mateos, L. (Leticia); Sesma, M.T. (María Teresa); Razquin, C. (Cristina); Gayoso, L. (Lucía); Ruiz-Canela, M. (Miguel); Vasilj, M. (María)Abstract Background & aims: To our knowledge the association between dietary advanced glycation end-products (dAGEs) and cardiometabolic disease is limited. Our aim was to examine the association between dAGEs and serum concentration of carboxymethyl-lysine (CML) or soluble receptor advanced glycation end-products (sRAGEs), and to assess the difference on dAGEs and circulating AGEs according to lifestyle and biochemical measures. Methods and results: 52 overweight or obese adults diagnosed with type 2 diabetes were included in this cross-sectional analysis. dAGEs were estimated from a Food Frequency Questionnaire (FFQ) or from a FFQ þ Home Cooking Frequency Questionnaire (HCFQ). Serum concentrations of CML and sRAGEs were measured by ELISA. Correlation tests were used to analyze the association between dAGEs derived from the FFQ or FFQ þ HCFQ and concentrations of CML or sRAGEs. Demographic characteristics, lifestyle factors and biochemical measures were analyzed according to sRAGEs and dAGEs using student t-test and ANCOVA. A significant inverse association was found between serum sRAGEs and dAGEs estimated using the FFQ þ HCFQ (r Z 0.36, p Z 0.010), whereas no association was found for dAGEs derived from the FFQ alone. No association was observed between CML and dAGEs. dAGEs intake estimated from the FFQ þ HCFQ was significantly higher among younger and male participants, and in those with higher BMI, higher Hb1Ac levels, longer time with type 2 diabetes, lower adherence to Mediterranean diet, and higher use of culinary techniques that generate more AGEs (all p values p < 0.05). Conclusions: These results show knowledge on culinary techniques is relevant to derive the association between dAGEs intake and cardiometabolic risk factors.
- Reshaping faecal gut microbiota composition by the intake of trans-resveratrol and quercetin in high-fat sucrose diet-fed rats(Elsevier, 2015) Martinez, J.A. (José Alfredo); Boque, N. (Noemi); Arias, N. (Noemi); Etxeberria, U. (Usune); Milagro-Yoldi, F.I. (Fermín Ignacio); Portillo, M.P. (María P.); Macarulla, M.T. (M. Teresa)Diet‐induced obesity is associated to an imbalance in the normal gut microbiota composition. Resveratrol and quercetin, widely known for their health beneficial properties, have low bioavailability and, when reach the colon, they are targets of the gut microbial ecosystem. Hence, the use of these molecules in obesity might be considered as a potential strategy to modulate intestinal bacterial composition. The purpose of this study was to determine whether trans‐resveratrol and quercetin administration could counteract gut microbiota dysbiosis produced by high‐fat sucrose diet (HFS) and in turn, improve gut health. Wistar rats were randomized into four groups fed a HFS diet supplemented or not with trans‐resveratrol (15 mg/kg BW/day), quercetin (30 mg/kg BW/day) or a combination of both polyphenols at those doses. Administration of both polyphenols together prevented body‐weight gain and reduced serum insulin levels. Moreover, individual supplementation of trans‐resveratrol and quercetin effectively reduced serum insulin levels and insulin resistance. Quercetin supplementation generated a great impact on gut microbiota composition at different taxonomic levels, attenuating Firmicutes/Bacteroidetes ratio and inhibiting the growth of bacterial species previously associated to diet‐induced obesity (Erysipelotrichaceae, Bacillus, Eubacterium 1 cylindroides). Overall, the administration of quercetin was found to be effective in lessening HFS diet‐induced gut microbiota dysbiosis. In contrast, trans‐resveratrol supplementation alone or in combination with quercetin, scarcely modified the profile of gut bacteria, but acted at intestinal level altering the mRNA expression of tight‐junction proteins (TJPs) and inflammation associated genes.
- Do the effects of resveratrol on thermogenic and oxidative capacities in IBAT and skeletal muscle depend on feeding conditions?(MDPI AG, 2018) Martinez, J.A. (José Alfredo); Etxeberria, U. (Usune); Milagro-Yoldi, F.I. (Fermín Ignacio); Milton-Laskibar, I. (Iñaki); Portillo, M.P. (María P.); Aguirre, L. (Leixuri)The aim of this study was to compare the effects of mild energy restriction and resveratrol on thermogenic and oxidative capacity in interscapular brown adipose tissue (IBAT) and in skeletal muscle. Rats were fed a high-fat high-sucrose diet for six weeks, and divided into four experimental groups fed a standard diet: a control group, a resveratrol-treated group, an energy-restricted group and an energy-restricted group treated with resveratrol. Weights of IBAT, gastrocnemius muscle and fat depots were measured. Activities of carnitine palmitoyltransferase (CPT) and citrate synthase (CS), protein levels of sirtuin (SIRT1 and 3), uncoupling proteins (UCP1 and 3), glucose transporter (GLUT4), mitochondrial transcription factor (TFAM), nuclear respiratory factor (NRF1), peroxisome proliferator-activated receptor (PPARα) and AMP activated protein kinase (AMPK) and peroxisome proliferator-activated receptor gamma coactivator (PGC1α) activation were measured. No changes in IBAT and gastrocnemius weights were found. Energy-restriction, but not resveratrol, decreased the weights of adipose depots. In IBAT, resveratrol enhanced thermogenesis activating the SIRT1/PGC1α/PPARα axis. Resveratrol also induced fatty acid oxidation and glucose uptake. These effects were similar when resveratrol was combined with energy restriction. In the case of gastrocnemius muscle, the effects were not as clear as in the case of IBAT. In this tissue, resveratrol increased oxidative capacity. The combination of resveratrol and energy restriction seemingly did not improve the effects induced by the polyphenol alone.
- Modulation of hyperglycemia and TNF[alfa]-mediated inflammation by helichrysum and grapefruit extracts in diabetic db/db mice(RSCPublishing, 2014) Martinez, J.A. (José Alfredo); Aumueller, E. (Eva); Etxeberria, U. (Usune); Milagro-Yoldi, F.I. (Fermín Ignacio); Haslberger, A.G. (Alexander G.); Palacios-Ortega, S. (Sara); Garza, A.L. (Ana Laura) de laType-2 diabetes is associated with a chronic low-grade systemic inflammation accompanied by an increased production of adipokines/cytokines by obese adipose tissue. The search for new antidiabetic drugs with different mechanisms of action, such as insulin sensitizers, insulin secretagogues and aglucosidase inhibitors, has directed the focus on the potential use of flavonoids in the management of type-2 diabetes. Thirty six diabetic male C57BL/6J db/db mice were fed a standard diet and randomly assigned into four experimental groups: non-treated control, (n ¼ 8); acarbose (5 mg per kg bw, n ¼ 8); helichrysum (1 g per kg bw, n ¼ 10) and grapefruit (0.5 g per kg bw, n ¼ 10) for 6 weeks. The mRNA expression in pancreas, liver and epididymal adipose tissue was determined by RT-PCR. DNA methylation was quantified in epididymal fat using pyrosequencing. Mice supplemented with helichrysum and grapefruit extracts showed a significant decrease in fasting glucose levels (p < 0.05). A possible mechanism of action could be the up-regulation of liver glucokinase (p < 0.05). The antihyperglycemic effect of both extracts was accompanied by decreased mRNA expression of some proinflammatory genes (monocyte chemotactic protein-1, tumor necrosis factor-a, cyclooxygenase-2, nuclear factorkappaB) in the liver and epididymal adipose tissue. The CpG3 site of TNFa, located 5 bp downstream of the transcription start site, showed increased DNA methylation in the grapefruit group compared with the non-treated group (p < 0.01). In conclusion, helichrysum and grapefruit extracts improved hyperglycemia through the regulation of glucose metabolism in the liver and reduction of the expression of proinflammatory genes in the liver and visceral fat. The hypermethylation of TNFa in adipose tissue may contribute to reduce the inflammation associated with diabetes and obesity.
- Metabolic faecal fingerprinting of trans-resveratrol and quercetin following a high-fat sucrose dietary model using liquid chromatography coupled to high-resolution mass spectrometry(Royal Society of Chemistry, 2015) Martinez, J.A. (José Alfredo); Boque, N. (Noemi); Arias, N. (Noemi); Etxeberria, U. (Usune); Milagro-Yoldi, F.I. (Fermín Ignacio); Portillo, M.P. (María P.); Macarulla, M.T. (M. Teresa); Romo‐Hualde, A. (Ana)Faecal non‐targeted metabolomics deciphers metabolic end‐products resulting from the interactions among food, host genetics, and gut microbiota. Faeces from Wistar rats fed a high‐fat sucrose (HFS) diet supplemented with trans‐resveratrol and quercetin (separately or combined) were analysed by liquid chromatography coupled to high‐resolution mass spectrometry (LC‐HRMS). Metabolomics in faeces are categorised into four clusters based on the type of treatment. Tentative identification of significantly differing metabolites highlighted the presence of carbohydrate derivatives or conjugates (3‐phenylpropyl glucosinolate and dTDP‐D‐mycaminose) in quercetin group. The trans‐resveratrol group was differentiated by compounds related to nucleotides (uridine monophosphate and 2,4‐dioxotetrahydropyrimidine D‐ribonucleotide). Marked associations between bacterial species (Clostridium genus) and the amount of some metabolites were identified. Moreover, trans‐resveratrol and resveratrol‐derived microbial metabolites (dihydroresveratrol and lunularin) were also identified. Accordingly, this study confirms the usefulness of omics‐based techniques to discriminate individuals depending on the physiological effect of food constituents and represents an interesting tool to assess the impact of future personalized therapies.
- Shifts in microbiota species and fermentation products in a dietary model enriched in fat and sucrose(Wageningen Academic Publishers, 2015) Martinez, J.A. (José Alfredo); Boque, N. (Noemi); Arias, N. (Noemi); Etxeberria, U. (Usune); Milagro-Yoldi, F.I. (Fermín Ignacio); Portillo, M.P. (María P.); Macarulla, M.T. (M. Teresa)The gastrointestinal tract harbours a “superorganism” called the gut microbiota, which is known to play a crucial role in the onset and development of diverse diseases. This internal ecosystem, far from being a static environment, could be willingly manipulated by diet and dietary components. Feeding animals with high-fat sucrose diets entails diet-induced obesity, a model which is usually used in research to mimic the obese phenotype of Western societies. The aim of the present study was to identify gut microbiota dysbiosis and associated metabolic changes produced in 5 male Wistar rats fed a high-fat sucrose (HFS) diet for six weeks and to compare it with the basal microbial composition. For this purpose, DNA extracted from faeces at baseline and after the treatment was analysed by amplification of the V4-V6 region of the 16S ribosomal DNA (rDNA) gene using 454 pyrosequencing. Short-chain fatty acids (SCFA), acetate, propionate and butyrate, were also evaluated by gas chromatography-mass spectrometry (GC-MS). At the end of the treatment, gut microbiota composition significantly differed at phylum level (Firmicutes, Bacteroidetes and Proteobacteria) and class level (Erisypelotrichi, Deltaproteobacteria, Bacteroidia and Bacilli). Interestingly, Clostridia class showed a significant decrease after the HFS-diet treatment, which correlated with visceral adipose tissue, and is likely mediated by dietary carbohydrates. Of particular interest, Clostridium cluster XIVa species were significantly reduced and changes were identified in the relative abundance of other specific bacterial species (Mitsuokella jalaludinii, Eubacterium ventriosum, Clostridium sp. FCB90-3, Prevotella nanceiensis, Clostridium fusiformis, Clostridium sp. BNL1100 and Eubacterium cylindroides) that, in some cases, showed opposite trends to their relative families. These results highlight the relevance of characterizing gut microbial population differences at species level and contribute to understand the plausible link between the 1 diet and specific gut bacterial species that are able to influence the inflammatory status, intestinal barrier function and obesity development. Keywords: gut microbiota, pyrosequencing, high-fat sucrose diet, short chain fatty acids, Erysipelotrichi
- Development and validation of a new home cooking frequency questionnaire: A pilot study(MDPI, 2022) Martinez-Gonzalez, M.A. (Miguel Ángel); Etxeberria, U. (Usune); Pueyo-Garrigues, M. (María); Goñi-Mateos, L. (Leticia); Gayoso, L. (Lucía); Ruiz-Canela, M. (Miguel); Eisenberg, D.M. (David M.); Vasilj, M. (María); De-la-O-Pascual, V. (Víctor); Gil, M. (Mario)Home cooking and the type of cooking techniques can have an effect on our health. However, as far as we know, there is no questionnaire that measures in depth the frequency and type of cooking techniques used at home. Our aim was to design a new Home Cooking Frequency Questionnaire (HCFQ) and to preliminarily assess its psychometric properties. For this purpose we used a five-phase approach, as follows: Phase 1: item generation based on expert opinion, relevant literature and previous surveys; Phase 2: content validity assessed by experts for relevance and clarity (epidemiologists, dietitians, chefs); Phase 3: face validity and inter-item reliability; Phase 4: criterion validity using a 7-day food and culinary record; and Phase 5: test stability and inter-item reliability. The content validity index for scale and item level values provided evidence of the content validity for relevance and clarity. Criterion validity analysis showed intraclass correlation coefficients ranged from 0.31−0.69. Test−retest reliability coefficients ranged from 0.49−0.92, with ƙ values > 0.44. Overall Cronbach’s alpha was 0.90. In conclusion, the HCFQ is a promising tool with sound content and face validity, substantial criterion validity, and adequate reliability. This 174-item HCFQ is the first questionnaire to assess how often people cook and which cooking methods they use at home.
- Antidiabetic effects of natural plant extracts via inhibition of carbohydrate hydrolysis enzymes with emphasis on pancreatic alpha amylase(Informa Healthcare, 2012) Martinez, J.A. (José Alfredo); Etxeberria, U. (Usune); Milagro-Yoldi, F.I. (Fermín Ignacio); Campión-Zabalza, J. (Javier); Garza, A.L. (Ana Laura) de laIntroduction: The increasing prevalence of type 2 diabetes mellitus and the negative clinical outcomes observed with the commercially available anti-diabetic drugs have led to the investigation of new therapeutic approaches focused on controlling postprandrial glucose levels. The use of carbohydrate digestive enzyme inhibitors from natural resources could be a possible strategy to block dietary carbohydrate absorption with less adverse effects than synthetic drugs. Areas covered: This review covers the latest evidence regarding in vitro and in vivo studies in relation to pancreatic alpha-amylase inhibitors of plant origin, and presents bioactive compounds of phenolic nature that exhibit anti-amylase activity. Expert opinion: Pancreatic alpha-amylase inhibitors from traditional plant extracts are a promising tool for diabetes treatment. Many studies have confirmed the alpha-amylase inhibitory activity of plants and their bioactive compounds in vitro, but few studies corroborate these findings in rodents and very few in humans. Thus, despite some encouraging results, more research is required for developing a valuable anti-diabetic therapy using pancreatic alpha-amylase inhibitors of plant origin.