The first goal of this line of research is to identify new biomarkers, whether genetic (polymorphisms, issue copy), epigenetic (DNA methylation), transcriptomic (mRNA or microRNA expression), metagenomic (gut microbiota), proteomic or metabolomic/lipidomic. The ideal biomarker should provide diagnostic, prognostic and therapeutic information in addition to that obtained from the patient's clinical data .

Applications
The main applications are as follows:

- Early prognosis of the disease development .

- Prognosis of comorbidities associated with obesity.

- Diagnosis of obesity or associated comorbidities.

- Prognosis of response to treatment.

- Follow-up of weight loss after an intervention.

- Prognosis of recurrence of obesity-associated comorbidities.

At summary, the identification of new biomarkers is important because, on the one hand, it allows determining an individual's susceptibility to develop obesity, diabetes subject 2 and other related problems and, on the other hand, it allows optimising treatment through the implementation of personalised treatments.

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

• Nutrigenetics (SNPs, variants of issue copy variants,...)
• Nutriepigenetics
• Transcriptomics / Nutrigenomics (mRNA)
• miRNAomics (miRNA)
• Metagenomics (gut microbiota)
• Metabolomics / Lipidomics

The second goal of this line of research is the identification, characterisation and study of the biological activity of various 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 to both the food and pharmaceutical industry, as they can be the basis for the development of new dietary supplements or functional foods. To this end, programs of study activity of new extracts or molecules in various models (in vitro, C. elegans, rat/mouse, etc.) is developed in order to select candidates for subsequent assessment in programs of study of nutritional intervention in humans, as well as to study the possible 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 obesity-related diseases and their associated metabolic comorbidities (insulin resistance, non-alcoholic fatty liver disease, metabolic syndrome, among others).

Lines of research

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

• programs of study of mechanisms of action.

• programs of study efficacy and bioavailability in animal models

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

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

This research requires a cross-cutting approach and multidisciplinary, employing a wide variety of models (from cell cultures to animal and human models) and technologies (especially the use of omics technologies such as microarrays and next-generation sequencing), as well as complex bioinformatics and statistical analyses.

Applications
The main application is:

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

Lines of research

• research of dietary and lifestyle factors that alter the gut-liver-brain axis, including gut permeability and inflammation under Degree, and the study of the modulatory effects of dietary compounds and foods on the composition of the gut microbiota.

• Analysis of gene-environment interactions converging on the metabolism-epigenome-genome axis, and study of epigenetic changes induced by the ingestion of different diets, foods and bioactive compounds in various cell types.

reference letter: 0011-1411-2021-000100

Funding Entity: department de development Economic and Business. Grants for the implementation of strategic projects of research and development 2021-2024. challenge 4. ALPES IV. Personalised and Sustainable Food.

researcher principal: Dr. Fermín I. Milagro Yoldi.

Consortium: ALIMENTOS SANYGRAN, S.L. (coordinator), AN, S. COOP., TUTTI PASTA, S.A., APERITIVOS Y EXTRUSIONADOS, S.A., association CLUSTER AGROALIMENTARIO DE NAVARRA (NAGRIFOOD) , UNIVERSIDAD PÚBLICA DE NAVARRA, UNIVERSIDAD DE NAVARRA

Duration: 2021-2023.

This project, financed by the Government of Navarra with 1.3 million euros and with a duration of 3 years has as goal the research of new ingredients and nutritionally healthy foods obtained by applying the circular Economics in sustainable production systems of crops with high environmental interest and by-products from Navarra, adapting them to consumer demand in terms of organoleptic, nutrition, health, convenience and cost.

At project, alternative crops and by-products generated in the region that provide high protein, fibre and/or bioactive compounds of interest and that also meet specific nutritional requirements for the protection and improvement of health will be used.

reference letter: 0011-1411-2021-000106

Funding Entity: department de development Economic and Business. Grants for the implementation of strategic projects of research and development 2021-2024. challenge 4. SIBERIA III. Innovative Biotechnology Solutions for Energy, Health Challenges, Industry and Agri-Food.

researcher principal: Dr. Fermín I. Milagro Yoldi.

Consortium: FUNDACIÓN PARA LA research MÉDICA ALICADA (coordinator), FUNDACIÓN ADITECH, NUCAPS NANOTECHNOLOGY, S.L., CENTRO NACIONAL DE TECNOLOGÍA Y SEGURIDAD ALIMENTARIA (CNTA), FUNDACIÓN MIGUEL SERVET, UNIVERSIDAD DE NAVARRA

Duration: 2021-2023.

goal This project, funded by the Government of Navarra with 1.4 million euros and with a duration of 3 years, aims to generate a multi-omics platform and a set of bioinformatics tools to characterise the role of the microbiota in the physiopathology of diseases of great health value partner-health and in the response of patients to clinical or therapeutic interventions.

To achieve this goal, different agents are involved, such as hospitals (CHN, CUN), research centres (FMS, CIMA, CIMA LAB Diagnostics, CIN-UNAV), a technology centre (CNTA) and a business biotechnology company (NUCAPS).

The success of project, which also foresees its industrial valorisation, will allow progress to be made in the generation of tools for obtaining and data analysis omics, as well as in the development of new biotechnology-based therapeutic solutions.

reference letter: PC127-128 METHANOB

Funding Entity: department de Universidad, Innovación y Transformación Digital. Government of Navarra. Grants to Technology Centres and Research Bodies to carry out collaborative research and development projects (call for proposals 2020).

Funding: 171.760,50 €.

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

Consortium: UNIVERSITY OF NAVARRA (research center in Nutrition) and the National Centre for Food Technology and Safety (CNTA).

Duration: 2020-2021

summary:

Obesity is a serious public health problem that has reached epidemic proportions in many countries, with significant health and social costs. Thus, the identification and characterisation of new bioactive compounds of natural origin (CBAs) that can be added to food or administered as nutraceuticals is of great interest to limit and, to some extent, counteract the undesirable effects associated with obesity and overweight. However, one of the barriers to validate in vivo the effects demonstrated in vitro is their leave oral bioavailability due to their physicochemical characteristics and their significant presystemic metabolism.

This project aims to generate a concept test to use some of the metabolites generated by the colonic microbiota from CBAs described by bibliography in (nano)encapsulated form to improve their absorption, limit the variability in their bioavailability and avoid secondary metabolic modifications that may decrease their efficacy.

reference letter: MICROLIVER

Funding Entity: department de Universidad, Innovación y Transformación Digital. Government of Navarra. Grants to Technology Centres and Research Bodies to carry out collaborative research and development projects (call for proposals 2020).

Financing: 408,589.75 €.             

researcher main: Fermín Milagro

Consortium: UNAV, UPNA.

Duration: 2020-2022

summaryThe present project aims, on the one hand, to promote a disruptive advance in the study of the microbiome through the design of a non-invasive capsule (orally) that allows the taking of sample in different areas of the gastrointestinal tract. Secondly, this project is committed to development of new therapies for non-alcoholic fatty liver disease through the administration of encapsulated probiotics.

The work is divided into three main tasks:

1 - development of a device for taking sample at various locations in the gastrointestinal tract.

2 - Study of the effects of a combination of probiotics on a model fatty liver in rodents.

3 - Study of the effects of probiotics on a model of fatty liver in minipigs and validation of the device for taking sample

The effects of probiotic treatment on the microbiota and metabolome in porcine fatty liver model will be studied and the sampling device subject will be validated in a very common pathological status in humans.

One of the main contributions of this project lies in the design of a novel device that could be applied in humans to advance the therapy of diseases related to intestinal dysbiosis (obesity, diabetes, Crohn's, coeliac disease, intolerances, allergies, liver, cardiovascular and neurological diseases, colorectal cancer, surgeries, etc.).

reference letter: 2021-11

Funding Agency: Nutricia Research Foundation (41155715).

Financing: €29,355

researcher main: Paula Aranaz

Duration: November 2020 - October 2021

summary from project:

The present project aims to identify, through different omics technologies (metagenomics, metabolomics and lipidomics), metabolites of microbial origin in plasma of individuals with and without obesity that could be associated with the development of the different complications of the disease, such as visceral adiposity, dyslipidemia, insulin resistance, or inflammatory processes, among others. The possible postbiotic activity of the metabolites will be evaluated in vitro (cell cultures) and in vivo(C. elegans). The study aims to provide new insights into mechanisms by which gut microorganisms may be involved in the control of body weight and adiposity, and to open the door to new therapeutic approaches.

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

Funding Entity: department de development Económico. Government of Navarre. Aid for the implementation of strategic projects of research and development 2018-2020. challenge 4. ALPES I. Personalised and Sustainable Food.

researcher principal: Dr. Fermín I. Milagro Yoldi.

Consortium: INDUSTRIAS ALIMENTARIAS DE NAVARRA, S.A. (leader), ISANATUR, ACEITES URZANTE, ULTRACONGELADOS VIRTO, Centro Nacional de Tecnología y Seguridad Alimentaria (CNTA) and UNIVERSITY OF NAVARRA (research center in Nutrition, group of research in food and Genomics Service of CIMA LAB.

Duration: 2018-2020.

project budget 1.7 million, is based on the hypothesis that the ingestion of certain foods rich in various active ingredients can modulate the microbiota and thus improve the health of the population.

All entities in the consortium share the vision that health-oriented food can provide opportunities for differentiation and value creation. In this line, this project will provide scientific information that will allow participants to address new business lines (specialised product ranges, production of ingredients and extracts) and new products (fortified foods, plant extracts) focused on improving health through food.

Furthermore, this project will enable synergies to be established between the participants that can be exploited in the future, strengthening the partnership between the business fabric and the scientific-technological system of Navarre.

Reference: RTI2018-102205-B-I00

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

Fundingbody: Ministry of Science, Innovation and Universities. Projects of research Fundamental non-oriented.

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: Use of biotechnology for the production of health-promoting ingredients and foods

Fundingbody: department de development Económico. Government of Navarre. Grants for the implementation of strategic projects of research and development 2019-2021. challenge 7. SIBERIA I. Innovative solutions in biotechnology for energy, health challenges, industry and agri-food.

Lead researcher: Dr. Fermín I. MilagroYoldi.

Consortium: BIOSASUN, S.A. (leader), BROTALIA, GARUNKOOK, INBIOLEV, NUCAPS, Centro Nacional de Tecnología y Seguridad Alimentaria (CNTA) and UNIVERSITY OF NAVARRA (research center in Nutrition, group of research UNAV-NANOVAC, and Genomics Service of 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.

• Paula Aranaz Oroz - paranaz@unav.es

• Carlos de Miguel Vázquez - cdmiguel@unav.es

• Miguel López Yoldi - mlyoldi@unav.es

• Ana Lorente Nieva - alnieva@unav.es

• José Ignacio Riezu Boj - jiriezu@unav.es

• Amanda Cuevas Sierra - acsierra@unav.es

• Ester Díez Sainz

• Deyan Yavorov Daylie

design of kits and scores related to the diagnosis and prognosis of physiological states related to inflammatory status, obesity, nutritional quality (or adherence to a per diem expenses) and predisposition to metabolic diseases. In addition, design of kits for the personalisation of therapeutic strategies.

• Diagnostic and prognostic kits.

• Response or adherence kits at per diem expenses.

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

- Capable of reducing or delaying 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, preventing the creation of new adipose tissue and its hypertrophy.

- Able to increase energy expense , basal metabolism, thermogenesis and adipose tissue browning.

Identification of new bioactive compounds, food combining and dietary patterns:

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

- Able to modulate epigenetic alterations that are involved in metabolic report or are commonly observed in obesity and its complications.