/ Research Lines

Innovative therapeutics for immunometabolic conditions

About


Immunometabolism: Where Immunology and Metabolism Meet.

In the last two decades, “Immunometabolism” has emerged as a continuously increasing area of research with substantial impact on biomedicine. Evolutionarily conserved interactions between immune responses and metabolism continuously sense the intake of nutrients and xenobiotics (e.g. drugs, nutraceuticals, addictives) in the gut through microbiota eco-system network and intestinal immunity, the first immune point of contact. Distal effects are noticed on key target tissues such as the liver, pancreas, kidney, heart or brain of most non-communicable disorders typically featured by chronic low-grade inflammation, from auto-immune disorders to metabolic-renal-vascular conditions. Accordingly, innovative strategies to fine tune gut microbiota, immunometabolism and low-grade inflammation are a promising segment of next-generation therapeutics worldwide.

Main achievements


1. Blueberry agrowaste prebiotic fiber benefits gut microbiota-immune system interplay and corrects systemic dysmetabolic conditions and central remyelination in animal models of T2DM and Multiple Sclerosis (Ms in preparation)

2. Gut-liver-kidney axis is impaired by low-fat purified dietary interventions raising awareness on the use of this isocaloric nutrient-match control diet in in vivo preclinical studies (Ms in preparation)

3. A stress-free, metabolic inert and precise oral dosing technology – HaPILLness – foster the 3Rs algorithm implementation in in vivo preclinical assays of safety and efficacy (Ms in preparation; Patent pending: PCT/IB2021/053124 – 116301)

4. BODIPY fluorescent-based protocol for lipid droplet characterization allows the successful discrimination of microvesicular and macrovesicular steatosis and may represent a complementary approach to the classical histological protocols for hepatic steatosis assessment (JOVE, 2023)

5. In opposition to what has been observed in healthy rats, chronic blueberry juice supplementation was able to improve hepatic mitochondrial energetics in prediabetic animals (Pharmaceutics, 2020; Nutrients, 2021).

Publications

Scientific interests and ongoing research projects


1. Innovative therapeutics and nutraceuticals: To develop and validate microbiota-based interventions, in a circular economy perspective, to tackle the increased incidence of non-communicable immunomediated diseases, from auto-immune disorders to metabolic-renal-microvascular dysfunctions. We progress on the valorization of agrowastes and by-products as suppliers to obtain biomass-based products for food and nutraceutical production chains.

Ongoing Projects:

  • Bioconversion of blueberry-based agrowastes into functional ingredients with improved immunonutritional value in chronic kidney disease

  • Blueberry leaf biomass: a nutraceutical for multiple sclerosis’ relief by targeting the gut-immune-CNS axis

  • Beneficial effects of Faecalibacterium prausnitzii and Akkermansia muciniphila delivery systems in inflammatory bowel disease and prediabetes rodent models

  • Capturing high value from industrial fermentation bioproduts: impact on models of inflammatory bowel disease, prediabetes and anemia

2. Refinement of animal research: To refine in vivo pharmacological and toxicological assays, in a translational perspective, and uphold the humane use of animal used for scientific purposes. Given that pain and stress have been proven to alter animal behavior and physiology (e.g. immune and stress-responsive pathways) and potentially lead to unreliable data, we developed an innovative technology – HaPILLness – a stress-free and metabolic-inert solution for voluntary oral dosing.

Ongoing Projects:

  • A voluntary semi-solid PILL approach for rodent drug dosing - 3R's in motion (Patent pending: PCT/IB2021/053124 – 116301)

3. Disease biomarkers: Gut microbial ecosystem, both communities and their metabolites, greatly contribute to local mucosal homeostasis by maintaining the balance between host defense and immune tolerance. We seek to disentangle the complex host-microbe-immune interactions, with emphasis on gut-associated lymphoid tissue, in order to identify key-targets that influence the susceptibility of the host to a large number of immunometabolic conditions, chronic immunosenescence and low-grade inflammation.

Ongoing Projects:

  • New biomarkers for early chronic kidney disease diagnosis and monitoring
  • Biomarkers for gadolinium-induced renal injury

4. Cocreation approaches and tools for the promotion of health literacy: Low levels of literacy in general, and insufficient knowledge in health and digital fields in particular, are prevalent among the elderly population and closely linked with poor healthy lifestyle habits, greater isolation, loss of quality of life and an increased risk of frailty and chronic diseases. New forms of teaching and learning, based on inclusive, appealing and interactive methodologies fostered by designed frameworks and tools well-suited to the needs of the recipients, in co-creation with them, are essential to improve the adherence of populations with low literacy, especially the elderly, to programs aimed at improving literacy in general and for health in particular.

Ongoing Projects:

  • LOLit – Low Literacy at Play

5. Technology-based Spin-off

Incubated at Instituto Pedro Nunes (IPN)

Team

Group Leader

PhD Members

SV
Sofia Viana
RM
Rui Alves, MD
HM
Helena Sá, MD
SN
Sara Nunes

Other members

VA
Vera Alves
KG
Karina Garcia
RA
Raquel Albuquerque
PV
Pedro Vieira