Open Access
Antidiabetic effects of Pediococcus acidilactici pA1c on HFD-induced mice
(MDPI, 2022) Cabello Olmo, Miriam; Oneca Agurruza, María; Pajares Villandiego, María Josefa; Jiménez, Maddalen; Ayo, Josune; Encío Martínez, Ignacio; Barajas Vélez, Miguel Ángel; Araña Ciordia, Miriam; Ciencias de la Salud; Osasun Zientziak; Gobierno de Navarra / Nafarroako Gobernua, 0011-1365-2020-000086
Prediabetes (PreD), which is associated with impaired glucose tolerance and fasting blood glucose, is a potential risk factor for type 2 diabetes mellitus (T2D). Growing evidence suggests the role of the gastrointestinal microbiota in both PreD and T2D, which opens the possibility for a novel nutritional approach, based on probiotics, for improving glucose regulation and delaying disease progression of PreD to T2D. In this light, the present study aimed to assess the antidiabetic properties of Pediococcus acidilactici (pA1c) in a murine model of high-fat diet (HFD)-induced T2D. For that purpose, C57BL/6 mice were given HFD enriched with either probiotic (1 × 1010 CFU/day) or placebo for 12 weeks. We determined body weight, fasting blood glucose, glucose tolerance, HOMA-IR and HOMA-β index, C-peptide, GLP-1, leptin, and lipid profile. We also measured hepatic gene expression (G6P, PEPCK, GCK, IL-1β, and IL-6) and examined pancreatic and intestinal histology (% of GLP-1+ cells, % of goblet cells and villus length). We found that pA1c supplementation significantly attenuated body weight gain, mitigated glucose dysregulation by reducing fasting blood glucose levels, glucose tolerance test, leptin levels, and insulin resistance, increased C-peptide and GLP-1 levels, enhanced pancreatic function, and improved intestinal histology. These findings indicate that pA1c improved HFD-induced T2D derived insulin resistance and intestinal histology, as well as protected from body weight increase. Together, our study proposes that pA1c may be a promising new dietary management strategy to improve metabolic disorders in PreD and T2D.
Open Access
Human microbiota network: unveiling potential crosstalk between the different microbiota ecosystems and their role in health and disease
(MDPI, 2021) Martínez, José E.; Vargas González, Augusto; Pérez Sánchez, Tania; Encío Martínez, Ignacio; Cabello Olmo, Miriam; Barajas Vélez, Miguel Ángel; Ciencias de la Salud; Osasun Zientziak
The human body is host to a large number of microorganisms which conform the human microbiota, that is known to play an important role in health and disease. Although most of the microorganisms that coexist with us are located in the gut, microbial cells present in other locations (like skin, respiratory tract, genitourinary tract, and the vaginal zone in women) also play a significant role regulating host health. The fact that there are different kinds of microbiota in different body areas does not mean they are independent. It is plausible that connection exist, and different studies have shown that the microbiota present in different zones of the human body has the capability of communicating through secondary metabolites. In this sense, dysbiosis in one body compartment may negatively affect distal areas and contribute to the development of diseases. Accordingly, it could be hypothesized that the whole set of microbial cells that inhabit the human body form a system, and the dialogue between the different host microbiotas may be a contributing factor for the susceptibility to developing diseased states. For this reason, the present review aims to integrate the available literature on the relationship between the different human microbiotas and understand how changes in the microbiota in one body region can influence other microbiota communities in a bidirectional process. The findings suggest that the different microbiotas may act in a coordinated way to decisively influence human well-being. This new integrative paradigm opens new insights in the microbiota field of research and its relationship with human health that should be taken into account in future studies.
Open Access
New insights into immunotherapy strategies for treating autoimmune diabetes
(MDPI, 2019) Cabello Olmo, Miriam; Araña Ciordia, Miriam; Radichev, Ilian; Smith, Paul; Huarte, Eduardo; Barajas Vélez, Miguel Ángel; Ciencias de la Salud; Osasun Zientziak; Gobierno de Navarra / Nafarroako Gobernua
Type 1 diabetes mellitus (T1D) is an autoimmune illness that affects millions of patients worldwide. The main characteristic of this disease is the destruction of pancreatic insulin-producing beta cells that occurs due to the aberrant activation of different immune effector cells. Currently, T1D is treated by lifelong administration of novel versions of insulin that have been developed recently; however, new approaches that could address the underlying mechanisms responsible for beta cell destruction have been extensively investigated. The strategies based on immunotherapies have recently been incorporated into a panel of existing treatments for T1D, in order to block T-cell responses against beta cell antigens that are very common during the onset and development of T1D. However, a complete preservation of beta cell mass as well as insulin independency is still elusive. As a result, there is no existing T1D targeted immunotherapy able to replace standard insulin administration. Presently, a number of novel therapy strategies are pursuing the goals of beta cell protection and normoglycemia. In the present review we explore the current state of immunotherapy in T1D by highlighting the most important studies in this field, and envision novel strategies that could be used to treat T1D in the future.
Open Access
A combination of apple vinegar drink with Bacillus coagulans ameliorates high fat diet-induced body weight gain, insulin resistance and hepatic steatosis
(MDPI, 2020) Urtasun Alonso, Raquel; Araña Ciordia, Miriam; Pajares Villandiego, María Josefa; Oneca Agurruza, María; Torre Hernández, Paloma; Barajas Vélez, Miguel Ángel; Encío Martínez, Ignacio; Ciencias de la Salud; Osasun Zientziak; Ciencias; Zientziak; Gobierno de Navarra / Nafarroako Gobernua
Obesity is a worldwide epidemic characterized by excessive fat accumulation, associated with multiple comorbidities and complications. Emerging evidence points to gut microbiome as a driving force in the pathogenesis of obesity. Vinegar intake, a traditional remedy source of exogenous acetate, has been shown to improve glycemic control and to have anti-obesity effects. New functional foods may be developed by supplementing traditional food with probiotics. B. coagulans is a suitable choice because of its resistance to high temperatures. To analyze the possible synergic effect of Vinegar and B. coagulans against the metabolic alterations induced by a high fat diet (HFD), we fed twelve-week-old C57BL/6 mice with HFD for 5 weeks after 2 weeks of acclimation on a normal diet. Then, food intake, body weight, blood biochemical parameters, histology and liver inflammatory markers were analyzed. Although vinegar drink, either alone or supplemented with B. coagulans, reduced food intake, attenuated body weight gain and enhanced glucose tolerance, only the supplemented drink improved the lipid serum profile and prevented hepatic HFD-induced overexpression of CD36, IL-1β, IL-6, LXR and SREBP, thus reducing lipid deposition in the liver. The beneficial properties of the B. coagulans-supplemented vinegar appear to be mediated by a reduction in insulin and leptin circulating levels.
Open Access
Development, analysis, and sensory evaluation of improved bread fortified with a plant-based fermented food product
(MDPI, 2023) Cabello Olmo, Miriam; Krishnan, Padmanaban G.; Araña Ciordia, Miriam; Oneca Agurruza, María; Díaz, Jesús Vicente; Barajas Vélez, Miguel Ángel; Rovai, Maristela; Ciencias de la Salud; Osasun Zientziak
In response to the demand for healthier foods in the current market, this study aimed to develop a new bread product using a fermented food product (FFP), a plant-based product composed of soya flour, alfalfa meal, barley sprouts, and viable microorganisms that showed beneficial effects in previous studies. White bread products prepared with three different substitution levels (5, 10, and 15%) of FFP were evaluated for physical characteristics (loaf peak height, length, width), color indices (lightness, redness/greenness, yellowness/blueness), quality properties (loaf mass, volume, specific volume), protein content, crumb digital image analysis, and sensory characteristics. The results revealed that FFP significantly affected all studied parameters, and in most cases, there was a dose–response effect. FFP supplementation affected the nutritional profile and increased the protein content (p < 0.001). The sensory test indicated that consumer acceptance of the studied sensory attributes differed significantly between groups, and bread with high levels of FFP (10 and 15% FFP) was generally more poorly rated than the control (0%) and 5% FFP for most of the variables studied. Despite this, all groups received acceptable scores (overall liking score ≥ 5) from consumers. The sensory analysis concluded that there is a possible niche in the market for these improved versions of bread products.
Open Access
A fermented food product containing lactic acid bacteria protects ZDF rats from the development of type 2 diabetes
(MDPI, 2019) Cabello Olmo, Miriam; Oneca Agurruza, María; Torre Hernández, Paloma; Sainz, Neira; Moreno Aliaga, María J.; Guruceaga, Elizabeth; Díaz, Jesús Vicente; Encío Martínez, Ignacio; Barajas Vélez, Miguel Ángel; Araña Ciordia, Miriam; Ciencias de la Salud; Osasun Zientziak; Ciencias; Zientziak; Gobierno de Navarra / Nafarroako Gobernua
Type 2 diabetes (T2D) is a complex metabolic disease, which involves a maintained hyperglycemia due to the development of an insulin resistance process. Among multiple risk factors, host intestinal microbiota has received increasing attention in T2D etiology and progression. In the present study, we have explored the effect of long-term supplementation with a non-dairy fermented food product (FFP) in Zucker Diabetic and Fatty (ZDF) rats T2D model. The supplementation with FFP induced an improvement in glucose homeostasis according to the results obtained from fasting blood glucose levels, glucose tolerance test, and pancreatic function. Importantly, a significantly reduced intestinal glucose absorption was found in the FFP-treated rats. Supplemented animals also showed a greater survival suggesting a better health status as a result of the FFP intake. Some dissimilarities have been observed in the gut microbiota population between control and FFP-treated rats, and interestingly a tendency for better cardiometabolic markers values was appreciated in this group. However, no significant differences were observed in body weight, body composition, or food intake between groups. These findings suggest that FFP induced gut microbiota modifications in ZDF rats that improved glucose metabolism and protected from T2D development.
Open Access
Comparison of 0.12% chlorhexidine and a new bone bioactive liquid, BBL, in mouthwash for oral wound healing: a randomized, double blind clinical human trial
(MDPI, 2022) Ferrés‐Amat, Eduard; Al Madhoun, Ashraf; Ferrés-Amat, Elvira; Carrió, Neus; Barajas Vélez, Miguel Ángel; Al-Madhoun, Areej Said; Ferrés-Padró, Eduard; Marti, Carles; Atari, Maher; Ciencias de la Salud; Osasun Zientziak; Universidad Pública de Navarra / Nafarroako Unibertsitate Publikoa, OTRI project, reference number 2020907094
Following surgery, healing within the oral cavity occurs in a hostile environment, and proper oral care and hygiene are required to accelerate recovery. The aim of the current study is to investigate and compare the bioreactivity characteristics of mouthwashes based on either chlorhexidine (CHX) or a novel bone bioactive liquid (BBL) in terms of oral healing within seven days application post-surgery. A randomized, double blind clinical trial was conducted in 81 patients, wherein the mouthwashes were applied twice a day for a period of 7 days. The visual analog scale (VAS) protocol was applied to determine pain index scores. Early wound healing index (EHI) score was determined for evaluating oral cavity healing progress. No adverse effects were observed using the mouthwashes, but CHX application resulted in stained teeth. Applications of both CHX and BBL were sufficient to reduce pain over a period of 7 days. However, the BBL group demonstrated a statistically significant reduction in VAS scores starting on day 4. The EHI scores were significantly higher in the BBL group compared with the CHX group, independent of tooth location. No differences in either VAS or EHI scores due to gender were observed. Compared with the commercially available CHX mouthwash, application of the BBL mouthwash reduced pain and accelerated oral cavity healing to a greater extent, suggesting it effectively improves the oral cavity microenvironment at the wound site in mediating soft tissue regeneration.
Open Access
Lactiplantibacillus plantarum DSM20174 attenuates the progression of non-alcoholic fatty liver disease by modulating gut microbiota, improving metabolic risk factors, and attenuating adipose inflammation
(MDPI, 2022) Riezu Boj, José I.; Barajas Vélez, Miguel Ángel; Pérez Sánchez, Tania; Pajares Villandiego, María Josefa; Araña Ciordia, Miriam; Milagro Yoldi, F. I.; Urtasun Alonso, Raquel; Ciencias de la Salud; Osasun Zientziak
Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease, reaching epidemic proportions worldwide. Targeting the gut–adipose tissue–liver axis by modulating the gut microbiota can be a promising therapeutic approach in NAFLD. Lactiplantibacillus plantarum, a potent lactic-acid-producing bacterium, has been shown to attenuate NAFLD. However, to our knowledge, the possible effect of the Lactiplantibacillus plantarum strain DSM20174 (L.p. DSM20174) on the gut–adipose tissue axis, diminishing inflammatory mediators as fuel for NAFLD progression, is still unknown. Using a NAFLD mouse model fed a high-fat, high-fructose (HFHF) diet for 10 weeks, we show that L.p DSM20174 supplementation of HFHF mice prevented weight gain, improved glucose and lipid homeostasis, and reduced white adipose inflammation and NAFLD progression. Furthermore, 16S rRNA gene sequencing of the faecal microbiota suggested that treatment of HFHF-fed mice with L.p DSM20174 changed the diversity and altered specific bacterial taxa at the levels of family, genus, and species in the gut microbiota. In conclusion, the beneficial effects of L.p DSM20174 in preventing fatty liver progression may be related to modulations in the composition and potential function of gut microbiota associated with lower metabolic risk factors and a reduced M1-like/M2-like ratio of macrophages and proinflammatory cytokine expression in white adipose tissue and liver.
Open Access
Experimental pilot study after surgery on a food supplement for athletes to protect articular knee cartilage. A functional and biochemical study
(Federación Española de Medicina del Deporte, 2021) Alfaro Adrián, Jesús; Araña Ciordia, Miriam; Barajas Vélez, Miguel Ángel; Ciencias de la Salud; Osasun Zientziak
En este estudio experimental doble ciego se evalúa la eficacia de la suplementación condroprotectora (Carticure Plus®, 5000 mg Colágeno (Péptidos Bioactivos) altamente asimilable, 1500 mg Glucosamina clorhidrato, 1200 mg Condroitín sulfato, 1,1 mg Cobre, 80 mg Vitamina C, 2 mg Manganeso) en pacientes con patología ligamentosa y meniscal que han requerido cirugía artroscópica. Se seleccionaron 12 pacientes con lesión ligamentosa y 12 pacientes con meniscopatía a los que se les procedió a la medición de distintos marcadores inflamatorios mediante ELISA, colágeno 2A y ácido hialurónico, además de a la evalua¬ción del dolor así como la funcionalidad y calidad de vida a través de EVA (Escala Visual Analógica), WOMAC (Western Ontario McMaster Universities Osteoarthritis Index) y KOOS (Knee Injury and Osteoarthritis Outcome Score). Se observaron diferencias estadísticamente significativas de mejoría clínica a favor de Carticure Plus®, con una mejora de la capacidad funcional de la escala WOMAC del 76 % frente a un 53% del placebo para el conjunto de pacientes y con una clara mejoría en el primer mes en lesión meniscal, en mejora de las actividades de la vida diaria (KOOS), Carticure Plus® 31% frente a placebo -1%, actividad deportiva (Carticure Plus® 41% vs Placebo 13,2%), actividades deportivas y recreativas (Carticure Plus® 128% vs Placebo 10,4%). Por otro lado, en lesión ligamentosa se observa una mejoría en calidad de vida (KOOS) Carticure Plus® 75% vs Placebo -8,8% y dolor (KOOS) Carticure Plus® 49,6% vs Placebo 0,3% en el primer mes respecto al basal. En el conjunto de pacientes, el dolor (KOOS) Carticure Plus® 31,4% vs Placebo 1,3% y actividades de la vida diaria (KOOS) Carticure Plus® 43,9% vs Placebo 27,1% en el tercer mes respecto al basal se asocian a una mejora a Carticure Plus® en comparación al placebo. A pesar del pequeño tamaño muestral, es destacable el hecho de haber encontrado diferencias estadísticamente significativas que podría presu¬poner la eficacia de Carticure Plus®.
Open Access
ONECUT2 is a druggable driver of luminal to basal breast cancer plasticity
(Sringer, 2024-05-31) Zamora Álvarez, Irene; Gutiérrez Núñez, Mirian; Pascual, Alex; Pajares Villandiego, María Josefa; Barajas Vélez, Miguel Ángel; Perez, Lillian M.; You, Sungyong; Knudsen, Beatrice S.; Freeman, Michael R.; Encío Martínez, Ignacio; Rotinen Díaz, Mirja Sofia; Ciencias de la Salud; Osasun Zientziak; Institute for Multidisciplinary Research in Applied Biology - IMAB; Gobierno de Navarra / Nafarroako Gobernua
Purpose: tumor heterogeneity complicates patient treatment and can be due to transitioning of cancer cells across phenotypic cell states. This process is associated with the acquisition of independence from an oncogenic driver, such as the estrogen receptor (ER) in breast cancer (BC), resulting in tumor progression, therapeutic failure and metastatic spread. The transcription factor ONECUT2 (OC2) has been shown to be a master regulator protein of metastatic castration-resistant prostate cancer (mCRPC) tumors that promotes lineage plasticity to a drug-resistant neuroendocrine (NEPC) phenotype. Here, we investigate the role of OC2 in the dynamic conversion between different molecular subtypes in BC. Methods: we analyze OC2 expression and clinical significance in BC using public databases and immunohistochemical staining. In vitro, we perform RNA-Seq, RT-qPCR and western-blot after OC2 enforced expression. We also assess cellular effects of OC2 silencing and inhibition with a drug-like small molecule in vitro and in vivo. Results: OC2 is highly expressed in a substantial subset of hormone receptor negative human BC tumors and tamoxifen-resistant models, and is associated with poor clinical outcome, lymph node metastasis and heightened clinical stage. OC2 inhibits ER expression and activity, suppresses a gene expression program associated with luminal differentiation and activates a basal-like state at the gene expression level. We also show that OC2 is required for cell growth and survival in metastatic BC models and that it can be targeted with a small molecule inhibitor providing a novel therapeutic strategy for patients with OC2 active tumors. Conclusions: the transcription factor OC2 is a driver of BC heterogeneity and a potential drug target in distinct cell states within the breast tumors.