Nutrition, Inflammation and Metabolism: Integrated Strategies for Prevention and Treatment of Diseases (NUIM)

Leader: Dra. Judit Ribas

This line characterizes the mechanistic basis through which nutrients, dietary patterns, and bioactivecompounds alter biological processes at the molecular, cellular, and systems level.

It integrates multi-omicsplatforms, experimental model systems, bioinformatics, and computational modeling to identify pathways,regulatory networks, and biomarkers with translational potential.

A core function of this line is to generatemolecular resources (signature panels, candidate biomarkers, exploratory predictive models) that can bedeployed by the clinical, microbiome, lifestyle, and implementation lines.

Full-scale multi-omics campaigns,large-cohort biomarker validation studies, and the development of clinically deployable AI-based decision-support tools depend on group-held grants and on external funding that program activities will help secure;the transversal program supports these tasks through coordination, crossline data integration, and seed-level pilot work.

Task 1.1. Develop and apply experimental models (in vitro, in vivo, ex vivo) to dissect molecular and cellularmechanisms underlying diet-host interactions.

Within program scope: coordination of model-generatedhypotheses with clinical and cohort questions addressed in other lines.

Execution of experimental work issupported by group-held resources.

Task 1.2. Perform host-directed multi-omics analyses in clinical and population-based cohorts.

Within program scope: harmonization of analytical approaches across groups and support for small-scaleexploratory analyses through the pilot project call.

Full-scale multi-omics campaigns depend on externalfunding.

Task 1.3. Integrate multi-omics and clinical data to identify diet-associated inflammatory molecularsignatures.

Within program scope: shared pipeline development and maintenance of a common analyticalframework accessible to other lines, executable with existing bioinformatics resources and in-kind contributions.

Task 1.4. Identify and validate nutritional, molecular, and genetic biomarkers.

Within program scope:biomarker discovery work and initial validation using samples and data generated through pilot projectsand group-held studies.

Large-scale independent validation cohorts depend on external grants.

Task 1.5. Develop exploratory predictive models for personalized nutrition recommendations based onintegrated patient profiles.

Within program scope: proof-of-concept modeling work using cohort dataalready available through participating groups (i.e. sleep medicine cohorts contributed by L4, diabeticcohorts contributed by L3), generating preliminary results to support external grant applications.

Lifestyle variables contributed by L3 and L4 are incorporated as effect-modifying inputs.

Clinical validation of modeloutputs in prospective intervention settings is not within program scope and depends on future funding.

Task 1.6. Explore the application of artificial intelligence and machine learning methods to dietary responseprediction and decision-support.

Within program scope: methodological scoping, exploratory modeldevelopment using existing cohort data, and preparation of grant applications that would fund full modeldevelopment, prospective validation, and clinical deployment.

Development of clinically deployabledecision-support tools is explicitly not within program scope and is positioned as a subsequent phasecontingent on external funding.

Contribution to Task 2.2 in Research Line 2.

L1 contributes mechanistic dissection support to L2'sinvestigation of immunological mechanisms in the microbiota-gut-immune axis, applying pathway analysisand targeted omics to characterize molecular events downstream of microbiota-immune interactionsidentified by L2.

L1 does not lead study design or sample collection for this task.

Leader: Dra. Gemma Belli

This line studies the bidirectional relationship between diet, the gut microbiome, and host physiology.

Its scope covers microbial community composition and functional capacity, host-microbe metabolic crosstalk, immune modulation at the gut barrier and beyond, and the identification of microbiome-mediated mechanisms through which dietary exposures affect health.

The line generates microbiota phenotype data used by L1 (integrated host-microbe omics), L3 (secondary outcomes in clinical studies), and L4 (outcome variables in lifestyle-nutrition interaction analyses).

A defining feature is that the primary research question always concerns the microbial dimension; when the primary question shifts to a clinical disease outcome or a host molecular readout, the lead line shifts to L3 or L1 respectively.

Full-scale metagenomic campaigns are supported through group-held resources and external funding; the program contributes through the pilot call and through crossline integration of microbiome data with clinical and lifestyle phenotypes.

Task 2.1. Conduct observational studies to assess the effects of dietary patterns and specific nutrients on gut microbiota composition and function.

Within program scope: crossline coordination of microbiota measurement protocols and support for small exploratory studies through pilot funding.

Larger prospective cohort analyses and intervention studies with microbiota endpoints depend on group-held and external funding.

Task 2.2. Investigate immunological mechanisms within the microbiota-gut-immune axis, including pro-
inflammatory and tolerogenic pathways.

L2 leads study design and immunological assay work in appropriate experimental or clinical models using group-held resources.

L1 contributes pathway and network analysis support.

Task 2.3. Perform metagenomic analyses in clinical and population-based cohorts.

Primary ownership of studies in which the primary analytical question concerns microbial community structure, diversity, or functional gene content.

Sequencing capacity and analytical cost are supported by group-held grants and core facility access.

Contribution to Task 1.2 in Research Line 1.

L2 coordinates sample logistics and provides access to cohort material from studies conducted under Tasks 2.1 and 2.2, ensuring sample quality, annotation, and linkage to microbiome data so that L1 can perform integrated host-microbe analyses.

Contribution to Tasks 4.1, 4.2, and 4.3 in Research Line 4.

L2 provides microbiota outcome data for use in L4's analyses of how sleep, physical activity, stress, and environmental exposures modify the diet- microbiome relationship.

L2 does not lead lifestyle exposure characterization; it supplies the microbiome phenotype data that L4 uses as its outcome variable

Leader: Dra. Minerva Granado

This line evaluates the role of nutrition in the prevention, onset, progression, and management of acute and chronic diseases.

It is the primary clinical arm of the program, responsible for the design and execution of dietary intervention studies, measurement and interpretation of disease-relevant endpoints, and comparative evaluation of nutritional strategies across pathological conditions.

Its access to diverse clinical populations through affiliated hospitals, and existing cohorts, and the active participation of L3 researchers in the ILERVAS population cohort and its associated CIBERDEM-linked work, is the central resource that enables cross-pathology comparative work and that grounds the program's translational claims in large- scale, well-phenotyped patient data.

Crucially, randomized controlled trials and clinical intervention studies with disease endpoints are executed under externally funded group-held grants; the transversal program's role is to coordinate crossline participation in these studies, to integrate their outputs with the broader program's biomarker and microbiome work, and to seed smaller feasibility and pilot components through the internal call.

Task 3.1. Coordinate dietary and lifestyle intervention studies in controlled and real-world settings,
targeting clinical or disease outcomes.

L3 is responsible for protocol design, ethics submissions, patient recruitment, dietary prescription and monitoring, and primary outcome data collection across intervention studies.

These studies are funded through the groups' external grants.

The program contributes through coordination of crossline add-on measurements (notably L4 lifestyle measurement protocols and L1/L2 multi-omics sub-studies) and through pilot-level seed funding for feasibility work or for adding nutrition- related components to existing studies.

Task 3.2. Participate in and coordinate randomized controlled trials evaluating dietary patterns with disease-relevant clinical endpoints.

RCT execution (recruitment, intervention delivery, primary endpoint measurement, safety monitoring, statistical analysis) is supported by group-held external grants and by IRBLleida's clinical research infrastructure.

The transversal program's role is limited to coordinating crossline contributions (biomarker, microbiome, lifestyle sub-studies), supporting harmonization of dietary assessment across trials, and funding small exploratory add-ons through the pilot call where scientifically justified.

Task 3.3. Assess the effects of nutritional interventions on clinical, biochemical, and functional outcomes.

Measurement, clinical interpretation, and safety monitoring owned by L3 across program-linked intervention studies, funded through existing clinical and group resources.

Task 3.4. Compare the differential effects of nutritional strategies across multiple pathological conditions.

Within program scope: coordination of cross-pathology comparative analyses drawing on ongoing and completed studies across participating groups; preparation of systematic syntheses and position papers; and identification of cross-pathology hypotheses that can drive future external grant applications.

Contribution to Task 5.1 in Research Line 5.

L3 provides access to relevant patient populations and clinical endpoint expertise for nutraceutical studies led by L5, including co-design of outcome measurement and advisory input on safety monitoring.

Execution of nutraceutical clinical studies depends on group-held or externally funded resources.

Contribution to Task 6.1 in Research Line 6.

L3 provides clinical safety monitoring input within disease-specific contexts for adherence and implementation analyses conducted by L6.

Contribution to Task 1.4, 1.5 and 1.6 in Research Line 1.

L3 contributes clinical input to the exploratory decision-support modeling carried out by L1, defining clinically meaningful output formats and reviewing model outputs against clinical practice expectations.

Prospective clinical testing of any decision-support tool is outside program scope.

Leader: Dr. Jordi de Batlle

This line investigates how lifestyle factors modify the impact of nutrition on inflammatory tone, microbiome dynamics, and metabolic health.

The conceptual contribution is that lifestyle exposures are treated not as independent research objects but as modifiers and mediators of the nutrition-disease relationship.

The line draws primarily on the cohorts already available through participating groups (i.e. sleep medicine cohorts, and relevant subsets of the ILERVAS population cohort in which L4 researchers are active contributors), which provide objectively measured sleep, circadian, and physical activity data alongside dietary and clinical information in the same individuals.

These cohorts are group-held resources; the program's contribution is cross-line integration, harmonization of lifestyle measurement and/or analysis across intervention studies, and seed-level pilot work on lifestyle-nutrition interactions.

Task 4.1. Characterize sleep and circadian disruption as modifiers of diet-induced inflammatory and metabolic responses, using cohorts already available through participating groups (i.e. sleep medicine cohorts).

Within program scope: secondary analyses of existing data and small pilot studies embedded in
ongoing protocols.

Microbiome outcome data supplied by L2.

Task 4.2. Characterize physical activity patterns as modifiers of diet-induced inflammatory and metabolic
responses, using accelerometry data from existing cohorts.

Within program scope: secondary analyses and targeted pilot studies.

Microbiome outcome data supplied by L2.

Task 4.3. Characterize psychological stress and environmental exposures as modifiers of diet-induced inflammatory and metabolic responses, using existing cohort data and targeted sub-studies embedded within L3 intervention trials.

Within program scope: secondary analyses and coordination of stress and environmental measurement add-ons.

Microbiome outcome data supplied by L2.

Contribution to Task 3.1 in Research Line 3.

L4 contributes standardized lifestyle measurement protocols (validated sleep instruments, accelerometry, circadian timing markers, perceived stress instruments) to dietary intervention studies led by L3, embedded as covariates or effect-modifying variables.

L4 does not alter the primary outcome structure of L3 trials.

Contribution to Task 1.5 in Research Line 1.

L4 supplies the lifestyle component of the integrated patient profile that feeds into the personalized nutrition modeling work developed by L1, providing processed and harmonized sleep, circadian, physical activity, and stress variables.

Leader: Dr. Jose Serrano

This line covers the research pipeline from natural compound identification to preclinical and clinical proof of concept, with a strong emphasis on innovation and transfer to the agrifood and health sectors.

It bridges basic and applied research by identifying bioactive compounds, characterizing their bioavailability and safety, and evaluating efficacy.

Industrial co-development with agrifood partners is embedded in the research model.

The full pipeline, including clinical trials, is executed under group-held funding, industrial partnerships, and external competitive grants; the transversal program contributes coordination, cross-line integration (particularly with L3 for clinical endpoints), and seed-level pilot work.

Task 5.1. Coordinate the nutraceutical research pipeline: compound identification and characterization, bioavailability and safety assessment, mechanism-of-action studies, and efficacy evaluation.

Preclinical and clinical execution depends on group-held grants, industrial partnerships, and external competitive funding.

Within program scope: coordination of crossline contributions (L3 clinical input, L1 mechanistic analyses), support for early-stage feasibility studies through the pilot call, and strategic positioning for external grant applications.

Contribution to Task 6.1 in Research Line 6.

L5 provides nutraceutical-specific safety and bioavailability information to L6's adherence and implementation analyses in trials involving nutraceutical interventions.

Leader: Dra. Amalia Zapata

This line applies implementation science and behavioral research methods to generate evidence on how, why, and under what conditions evidence-based nutritional interventions reach patients and populations and achieve their intended effects in real-world clinical and community settings.

Its value lies in closing the translational gap between efficacious interventions identified in controlled trials and their effective delivery in practice.

The line does not run independent nutritional intervention trials; instead, it layers implementation and behavioral analysis onto studies led by L3 and L5, and it explores the design of deployable digital health instruments.

Full digital tool development and validation depend on external funding; the program contributes research outputs on behavioral determinants and implementation science, methodological input to L3 and L5 studies, and pilot-level prototyping as a research vehicle rather than as a production deliverable.

Task 6.1. Evaluate adherence, real-world effectiveness, and long-term sustainability of nutritional interventions across populations enrolled in L3 and L5 studies.

Within program scope: process evaluations, mixed-methods analyses, and implementation outcome measurement embedded in ongoing studies, supported through in-kind work and pilot-level seed funding.

Clinical safety monitoring supplied by L3 and L5 as described above.

Expected research outputs include peer-reviewed publications on adherence determinants, implementation fidelity, and cost-effectiveness of nutritional interventions in specific clinical populations, plus contributions to crossline methodological papers on process evaluation in nutrition research (funded through the Internal call for pilot projects).

Task 6.2. Investigate behavioral and implementation determinants of adherence to personalized nutritional interventions, using exploratory prototyping of digital delivery formats as a methodological vehicle.

Within program scope: application of behavior change theory to the design of nutritional intervention delivery, landscape reviews of existing digital tools for nutrition, and small-scale usability and acceptability studies of prototypes built on algorithms developed in Task 1.5.

Expected research outputs include peer-reviewed publications on behavioral determinants of adherence to personalized nutrition and on design principles for digital delivery of nutritional interventions.

Development of production-ready digital health applications, formal efficacy validation, and real-world deployment are not within program scope and depend on external funding that the program's exploratory research is designed to position.