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Nutriomics and Biomarkers

Nutriomics and Biomarkers

The main objective of this line of research, which forms part of the NUTRIBIOSIM research group (Nutridynamics and Bioactives in Metabolic Syndrome), is to identify, characterise and study the biological activity of different natural sources of bioactive compounds (BACs) with therapeutic potential or prevention of obesity and its associated comorbidities.

These BACs are of great interest both for the nutrition industry and the pharmaceutical industry as they could be the basis for the development of new medicines, supplements or functional foods.

The activities in this research area are aimed at research into products with greater efficiency, bioavailability or stability and with fewer side effects than those already known and that can be used in diseases related to obesity and its associated metabolic comorbidities (type II diabetes, cardiovascular disease, fatty liver and others).

To this end,  activity studies of new extracts or molecules in different models (C. elegans, rats/mice, etc.) are developed, with the aim of selecting candidates before they are evaluated in nutritional intervention studies in humans, as well as examining the potential mechanisms involved or their bioavailability.

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Research Areas

The first objective of this research line is to identify new biomarkers, whether they are genetic (polymorphisms, number of copies), epigenetic (methylation of DNA), transcriptomics (expression of mRNA or miRNA), metagenomic (gut microbiota), proteomic or metabolomic/lipidomic. The ideal biomarker should provide additional diagnostic, prognostic and therapeutic information to that obtained from the patient's clinical data.

Applications

The main applications are the following:

  • Early prognosis of disease development.

  • Prognosis of comorbidities associated with obesity.

  • Diagnosis of obesity or associated comorbidities.

  • Prognosis of response to treatment.

  • Monitoring the weight lost after an intervention.

  • Prognosis of recurrence of the comorbidities associated with obesity.

In summary, the identification of new biomarkers is important because it will, on the one hand, determine the susceptibility of an individual to develop obesity, type 2 diabetes and other related syndromes and, on the other, optimize the treatment through the implementation of personalized dietary of lifestyle strategies.

Research lines

Identification of biochemical, genetic, epigenetic, transcriptomic, proteomic, metabolomic, and metagenomic biomarkers related to the risk of developing comorbidities associated with obesity and the metabolic syndrome, and the personalization of the intervention.

    Nutrigenetics (SNPs, copy number variants,…)

    Nutriepigenetics

    Transcriptomics / Nutrigenomics (mRNA)

    miRNAomics (miRNA)

    Metagenomics (gut microbiota)

    Metabolomics / Lipidomics

Expected results

Design of kits and indexes related to the diagnosis and prognosis of physiological states related to the inflammatory state, obesity, nutritional quality (or adherence to a diet) and the predisposition to metabolic diseases. Also, to the personalization of therapeutic approaches.

  • Kits of diagnosis and prognosis

  • Kits of response or adherence to the diet

The second objective of this research line is the identification, characterization and study of the biological activity of diverse natural sources of bioactive compounds with potential application in the treatment or prevention of obesity and its associated comorbidities. These bioactive compounds are of great interest for both the food and the pharmaceutical industry, as they can be the basis for the development of new dietary supplements or functional foods. To this end, activity studies of new extracts or molecules are developed in various models (in vitro, C. elegans, rat / mouse, etc.) in order to select candidates prior to their evaluation in nutritional intervention studies in humans, as well as studying the potential mechanisms involved or their bioavailability.

Applications
The main application is:

Development of products with greater efficacy, bioavailability or stability and with fewer side effects than those already known and applicable in diseases related to obesity and their associated metabolic comorbidities (insulin resistance, non-alcoholic fatty liver disease, metabolic syndrome, among others).

Research lines
Screening of bioactive compounds (cell cultures, Caenorhabditis elegans, rodents)

Studies of mechanisms of action

Studies of efficacy and bioavailability in animal models

Expected results
Identification of new bioactive compounds useful in the control of body weight and the prevention of obesity and metabolic disturbances:

  • able to reduce or delay digestion and absorption of macronutrients.

  • with antioxidant and anti-inflammatory properties.

  • with lipolytic activity, which directly affect the release of fatty acids from adipose tissue.

  • with inhibitory action on adipogenesis, preventing the creation of new adipose tissue and its hypertrophy.

  • able to increase energy expenditure, basal metabolism and thermogenesis.

The third objective of this line is to modulate gut microbiota and epigenetic marks in a customized manner. The intake of foods and diets rich in various bioactive principles (especially non-digestible carbohydrates, certain types of fiber and polyphenols) can modulate the gut microbiota and, thereby, affect the health status of the population. In addition, numerous bioactive compounds and nutrients, including vitamins and minerals, fatty acids, fibers and polyphenols, are able to modulate epigenetic mechanisms that regulate gene expression and metabolism.

Both mechanisms, microbiota and epigenetics, are associated with the development of disease. But both are potentially reversible through nutritional factors, so it is important to deepen into the effects of diets, nutrients and bioactive compounds when redirecting the microbiome and epigenome to a more "healthy" state. The final goal is to design diets, ingredients and foods that can be used in the prevention or personalized treatment of obesity and its associated comorbidities.

This research requires a cross-cutting and multidisciplinary approach, with use of various models (from cell cultures to animal and human models) and technologies (especially the use of omics technologies such as microarrays and new generation sequencing) as well as complex bioinformatic and statistical analyzes.

Applications
The main application is:

Development of food ingredients and combinations with beneficial activity on gut microbiota composition and epigenetic marks.  

Research lines
Investigation of the dietary and lifestyle factors that alter the gut-liver-brain axis, including leaky gut and low-grade inflammation, and study of the modulatory effects of dietary compounds and foods on gut microbiota composition

Analysis of the gene-environment interactions that converge at the metabolic-epigenome-genome axis, and study of the epigenetic changes induced by the intake of different diets, foods and bioactive compounds

Expected results
Identification of new bioactive compounds, combination of foods and dietary patterns able to:

  • Reverse the dysbiotic states associated with obesity and metabolic disturbances.

  • Modulate the epigenetic alterations that are involved in the metabolic memory or are commonly observed in obesity and its complications.

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Projects

Referencia: PC127-128 METANOB

 

Entidad Financiadora: Departamento de Universidad, Innovación y Transformación Digital. Gobierno de Navarra. Ayudas a Centros tecnológicos y Organismos de investigación para la realización de proyectos de I+D colaborativos (convocatoria 2020).

Financiación: 171.760,50 €

Investigador principal: Dr. Carlos J. González Navarro/Dr. Juan M. Irache.

Consorcio: UNIVERSIDAD DE NAVARRA (Centro de Investigación en Nutrición) y Centro Nacional de Tecnología y Seguridad Alimentaria (CNTA).

 

Duración: 2020-2021

 

Resumen:

La obesidad es un serio problema de salud pública que ha alcanzado proporciones epidémicas en muchos países y cuyos costes derivados tanto sanitarios como sociales son muy significativos. Así, la identificación y caracterización de nuevos compuestos bioactivos de origen natural (CBAs) que puedan ser añadidos a alimentos o administrados como nutracéuticos es de gran interés para limitar y, en cierta medida, contrarrestar los efectos indeseables asociados a la obesidad y el sobrepeso. Sin embargo, una de las barreras para validar in vivo los efectos demostrados in vitro es su baja biodisponibilidad oral debido a sus características fisicoquímicas y su importante metabolismo presistémico.

Este proyecto pretende generar una prueba de concepto que permita utilizar algunos de los metabolitos generados por la microbiota del colon a partir de CBAs descritos por la bibliografía en forma (nano)encapsulada para mejorar su absorción, limitar la variabilidad en su biodisponibilidad y evitar modificaciones metabólicas secundarias que puedan disminuir su eficacia.

Referencia: MICROLIVER

 

Entidad Financiadora: Departamento de Universidad, Innovación y Transformación Digital. Gobierno de Navarra. Ayudas a Centros tecnológicos y Organismos de investigación para la realización de proyectos de I+D colaborativos (convocatoria 2020).

Financiación: 408.589,75 €             

Investigador principal: Fermín Milagro

 

Consorcio: UNAV, UPNA.

 

Duración: 2020-2022

 

Resumen: El presente proyecto persigue, por una parte, propiciar un avance disruptivo en el estudio del microbioma a través del diseño de una cápsula no invasiva (por vía oral) que permita la toma de muestra en diversas zonas del tracto gastrointestinal. En segundo lugar, este proyecto apuesta por el desarrollo de nuevas terapias para la enfermedad de hígado graso no alcohólico a través de la administración de probióticos encapsulados.

Los trabajos se encuadran en tres tareas principales:

1 - Desarrollo de un dispositivo para la toma de muestra en diversas localizaciones del tracto gastrointestinal

2 - Estudio de los efectos de una combinación de probióticos sobre un modelo de hígado graso en roedores

3 - Estudio de los efectos de los probióticos sobre un modelo de hígado graso en minipigs y validación del dispositivo para la toma de muestra

Se estudiarán los efectos del tratamiento con probióticos sobre la microbiota y el metaboloma en el modelo porcino de hígado graso y se validará el dispositivo de toma de muestras de materia intestinal en una situación patológica muy común en humanos.

Una de las principales aportaciones de este proyecto radica en el diseño de un novedoso dispositivo que podrá aplicarse en humanos para avanzar en la terapia de enfermedades relacionas con la disbiosis intestinal (obesidad, diabetes, Crohn, celiaquía, intolerancias, alergias, enfermedades hepáticas, cardiovasculares y neurológicas, cáncer colorrectal, cirugías, etc).

Referencia: 2021-11

Entidad Financiadora: Nutricia Research Foundation (41155715).

Financiación: 29.355 €

Investigador principal: Paula Aranaz

Duración: Noviembre 2020 - Octubre 2021

Resumen del proyecto:

El presente proyecto pretende identificar, a través de diferentes tecnologías ómicas (metagenómica, metabolómica y lipidómica), metabolitos de origen microbiano en plasma de individuos con y sin obesidad que podría estar asociada con el desarrollo de la diferentes complicaciones de la enfermedad, como la adiposidad visceral, dislipidemia, resistencia a la insulina, o procesos inflamatorios, entre otros. La posible actividad postbiótica de los metabolitos se evaluarán in vitro (cultivos celulares) e in vivo (C. elegans). El estudio pretende proporcionar nuevos conocimientos sobre mecanismos mediante los cuales los microorganismos intestinales pueden participar en el control del peso corporal y la adiposidad, y abrir la puerta a nuevas terapias enfoques.

Referencia: 0011-1411-2018-00026/00030/00032/00033/00034/00040

Entidad Financiadora: Departamento de Desarrollo Económico. Gobierno de Navarra. Ayudas para la realización de proyectos estratégicos de I+D 2018-2020. Reto 4. ALPES I. Alimentación Personalizada y Sostenible.

Investigador principal: Dr. Fermín I. Milagro Yoldi.

Consorcio: INDUSTRIAS ALIMENTARIAS DE NAVARRA, S.A. (líder), ISANATUR, ACEITES URZANTE, ULTRACONGELADOS VIRTO, Centro Nacional de Tecnología y Seguridad Alimentaria (CNTA) y UNIVERSIDAD DE NAVARRA (Centro de Investigación en Nutrición, Grupo de investigación en alimentos y Servicio de Genómica de CIMA LAB.

Duración: 2018-2020.

Este proyecto, con una duración de cerca de tres años y un presupuesto de 1,7 millones de euros, se basa en la hipótesis de que la ingesta de determinados alimentos ricos en diversos principios activos puede modular la microbiota y, con ello, mejorar el estado de salud de la población.

Todas las entidades del consorcio comparten la visión de que la alimentación orientada a la salud puede proporcionar oportunidades de diferenciación y creación de valor. En esta línea, este proyecto proporcionará información científica que permitirá a los participantes abordar nuevas líneas de negocio (gamas de productos especializadas, producción de ingredientes y extractos) y nuevos productos (alimentos enriquecidos, extractos vegetales) enfocados a la mejora de la salud a través de la alimentación.

Además, este proyecto permitirá establecer sinergias entre los participantes que podrán ser explotadas en el futuro, afianzando la colaboración entre el tejido empresarial y el sistema científico-tecnológico de Navarra.

Reference: RTI2018-102205-B-I00

Title: Mechanisms by which gut microbiota prevents obesity risk: postbiotics and miRNAs of microbial and food origin

Fundingbody: Ministerio de Ciencia, Innovación y Universidades. Proyectos de Investigación Fundamental no orientada.

Lead researchers: Dr. Fermín I. MilagroYoldi and Dr. José Ignacio RiezuBoj

Duration: 2019-2021.

The objective of the project, which has obtained a total grant of 120,000 euros for the period 2019-21, is to study the role that gut microbiota plays in the regulation of energy metabolism, both through the metabolites produced by the microbiota (known as postbiotics) and the miRNAs produced by the microbiota or from food.

Three types of long-term results are expected:

1 - New metagenomic, metabolomic and miRNAomic biomarkers useful in the early detection of people at high risk of obesity and their comorbidities.

2 - New probiotics and postbiotics that can contribute to weight control and body fat.

3 - miRNAs of food origin, bacterial or eukaryotic, which could lead to new therapeutic targets for the treatment of obesity.

Reference: 0011-1411-2019-000008/000013/000031/000038/000068/000075/00000083

Title: Uso de la biotecnología para la obtención de ingredientes y alimentos beneficiosos para la salud

Fundingbody: Departamento de Desarrollo Económico. Gobierno de Navarra. Ayudas para la realización de proyectos estratégicos de I+D 2019-2021. Reto 7. SIBERIA I. Soluciones innovadoras en biotecnología para energía, retos sanitarios, industria y agroalimentación.

Lead researcher: Dr. Fermín I. MilagroYoldi.

Consorcio: BIOSASUN, S.A. (líder), BROTALIA, GARUNKOOK, INBIOLEV, NUCAPS, Centro Nacional de Tecnología y Seguridad Alimentaria (CNTA) y UNIVERSIDAD DE NAVARRA (Centro de Investigación en Nutrición, Grupo de investigación UNAV-NANOVAC, y Servicio de Genómica de CIMA LAB).

Duration: 2019-2021.

This project, with a duration of about three years and a budget of 0.8 million euros, is based on the hypothesis that the intake of fermented foods and some microbiota-related compounds are able to improve the state of health of the population.

The general objective of the project is to generate knowledge about the influence of gut microbiota-related ingredients (probiotics and postbiotics) and fermented foods obtained from bioprocesses on human health.

This project will be the engine of innovative ideas that allow the Navarra’s industry to compete with more guarantees in a market as competitive as that of biotechnology applied to health challenges and agri-food.

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Research Team

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More information

Design of kits and indexes (scores) related to the diagnosis and prognosis of physiological states related to the inflammatory state, obesity, nutritional quality (or adherence to a diet) and the predisposition to metabolic diseases. Likewise, kits for the personalization of therapeutic strategies.

  • Diagnostic and prognosis kits.

  • Kits of response or adherence to the diet.

 

Identification of new bioactive compounds useful in the control of body weight and the prevention of metabolic disorders:

  • Able to reduce or delay the digestion and absorption of macronutrients.

  • With antioxidant and anti-inflammatory properties.

  • With lipolytic activity, which directly affects the release of fatty acids from adipose tissue.

  • With inhibitory action on adipogenesis, avoiding the creation of new adipose tissue and its hypertrophy.

  • Able to increase energy expenditure, basal metabolism, thermogenesis and beiging of adipose tissue.

 

Identification of new bioactive compounds, combination of foods and dietary patterns capable of:

  • Able to reverse the dysbiotic states associated with obesity and metabolic disorders.

  • Able to modulate the epigenetic alterations that are involved in metabolic memory or are commonly observed in obesity and its complications.