Nutrição, Metabolismo e Microbiota

Esta é uma linha de investigação dedicada aos estudos do Eixo Dieta-Microbiota-Metabolismo. que determina a resposta individual à dieta. O microbiota intestinal assume um papel chave na ligação entre nutrição, estilos de vida, saúde e doença e, por isso, trata-se de um novo alvo terapêutico. 
Com recurso a diferentes modelos de investigação pré-clínica (linhas celulares e modelos animais) e clínica, a técnicas analíticas (metabolómica, sequenciação e biologia molecular) pretende compreender de uma forma holística o efeito da dieta no organismo, e o papel central do microbiota nesta relação. Conhecer o impacto da matriz alimentar, dos nutrientes e dos não-nutrientes (p.e. fitoquímicos) no metabolismo e os mecanismos moleculares envolvidos, atendendo às interações metabólicas entre microbiota e hospedeiro, é fulcral para a manutenção do estado de saúde. 

Graphical Abstract
  • MONET: Unravelling Microbiota-gut-brain axis paintings in obesity-associated Neuroinflammation: the blackbErry signaTure study – Fundação para a Ciência e Tecnologia PTDC/BAA-AGR/7419/2020 - (2021-2024)

    Microbiota and its metabolites have been involved in the metabolic, inflammatory and behavioural features of obesity, but the molecular events linking the gut microbiota and the development of metabolic and behavioural disorders have been poorly evaluated in the context of obesity.

Metabolites produced from nutrients and other food compounds by intestinal bacteria have many metabolic, immune and neurological implications [6]. A dietary intervention with specific nutrients, probiotics or prebiotics that re-establishes the balance in gut microbiota and its functionality in terms of metabolite production, could represent an efficient strategy in obesity care management, inflammation control and subsequently an improvement of neurologic disorders.

Blackberries, which are naturally rich in flavonoids, specifically in anthocyanins, have already shown positive effects in improving cognitive function and antioxidant status in animal studies [7-9]. Nevertheless, the full potential of blackberry consumption as a whole fruit, with naturally prebiotic properties and with ability to improve neurologic outcomes is still to be demonstrated.

This project hypothesis is that prebiotic, according to the new concept of prebiotic, attenuates obesity-related metabolic and behavioural alterations, through the promotion of tryptophan metabolites such as kynurenine pathway intermediates, indole derivatives and also short chain fatty acids (SCFAs). Therefore, the objective of this project is to test the protective effect of blackberry (as a model of prebiotic) and to dissect the molecular mechanisms in an obesity context thanks to faecal material transfer (FMT) from obese patients to mice.

Understanding the involvement of gut microbiota and its metabolites in metabolic and neurological disorders associated with obesity is essential to design innovative and efficient novel therapeutic strategies targeting the highly prevalent pathological conditions.

  • MicroSpA & MicroRA: The role of microbiome on biological therapy efficacy in axial Spondyloarthritis and Rheumatoid Arthritis - a new paradigm

Spondyloarthritis (SpA) and Rheumatoid arthritis (RA) are among the most common chronic inflammatory rheumatic diseases. Introduction of Tumor Necrosis Factor alpha inhibitors (TNFi) to the therapeutic strategy improved acute inflammation and pain, but a significant percentage of patients develop severe adverse events or are still non responders or incomplete responders to these expensive treatments. There is an urgent need to identify new predictors of biological therapy response. Actually, it has been described the role of microbiota in some rheumatic diseases, however, clinical trials are scarce. Thus, this project aimed to evaluate the influence of oral and gut microbiota in the therapeutic response to biologic therapies, in axSpA, RA patients and healthy controls. It is expected to identify specific profiles of oral and gut microbiome and/or specific biochemical patterns that will be able to predict the response to TNFi therapy and, consequently, a better evidenced-based treatment.

  • MONET: Unravelling Microbiota-gut-brain axis paintings in obesity-associated Neuroinflammation: the blackbErry signaTure study – Fundação para a Ciência e Tecnologia PTDC/BAA-AGR/7419/2020 - (2021-2024)
  • cLabel+: “Alimentos inovadores “clean label” naturais, nutritivos e orientados para o consumidor” 46080 -  14/SI/2019 (2020-2023)
  • “Exploring the neuroprotective potential of grape-derived flavonoids in the prevention of Alzheimer disease (NeuroFlav)”- Ministeiro de Ciencia e Innovación Y Universidades - Espanha(2020-2023)
  • MOBFOOD – “Mobilização de conhecimento científico e tecnológico em resposta aos desafios do mercado agroalimentar” 024524 - LISBOA-01-0247-FEDER-024524 (2017-2020)
  • FEEDMI: the influence of infant-feeding on very preterm infant’s gut microbiota
  • MEDBIOME: The Effect of MEDiterranean Diet on the MicroBIOME of Individuals with Type 2 Diabetes
  •  “ANTHO4SKIN – New anthocyanin derivatives for technological applications in the cosmetic industry” – Fundação para a Ciência e Tecnologia PTDC/AGR-TEC/3078/2014 (2014-2017)
  •  “VINOFLAVO – Red wine flavonoids: bioavailability and biological properties” - Fundação para a Ciência e Tecnologia PTDC/AGR-TEC/2227/2012 (2013-2015)
  • “MYRTILLUS - Blueberry with innovation"  - QREN - ADI 13736 (2011-2013) 
  • “ACTIPEP – Production of new bioactive peptide extracts, from the dairy products hydrolysis and brewing industry, for the new functional ingredients development” – QREN - ADI 11531 (2010-2012) 
  • “Antioxidant and antiradical characterization of polyphenolic compounds; bioavailability, biological properties and cell signalling.” - Fundação para a Ciência e Tecnologia PTDC/QUI/65501/2006 (2009-2011)
  • "Obtention and characterization of extracts from plants rich in biologically active antioxidants, for their incorporation into functional beverages" PRIME/POCI 2010-IDEIA, nº 13-05-04-FDR-00020-EXTRAVIDA (2007-2008)

Moreira-Rosário A, Marques C, Pinheiro H, Araújo J, Ribeiro P, Rocha R, Mota I, Pestana D, Ribeiro R, Pereira A, Sousa MJ, Pereira-Leal J, Sousa J, Morais J, Teixeira D, Rocha JC, Silvestre M, Príncipe N, Gatta N, Amado J, Santos L, Maltez F, Boquinhas A, de Sousa G, Sarmento G, Granja C, Póvoa P, Faria A, Calhau C. Gut microbiota diversity and C-Reactive Protein are predictors of disease severity in COVID-19 patients,  Frontiers in Microbiology, 2021, accepted.

Morais J, Marques C, Faria A,  Teixeira D, Barreiros-Mota I,  Durão C,  Araújo J, Ismael S, Brito S, Cardoso M, Macedo I, Esmeralda Pereira, Teresa Tomé, Conceição Calhau. Influence of human milk on very preterms’ gut microbiota and alkaline phosphatase activity. Nutrients, 2021, 15, 1564.

Morais, J., Marques, C., Teixeira, D., Durão, C., Faria, A., Brito, S., Cardoso, M., Macedo, I., Pereira, E., Tomé, T., Calhau, C. Extremely preterm neonates have more Lactobacillus in meconium than very preterm neonates–the in utero microbial colonization hypothesis. 2020 Gut Microbes, pp. 1-9.

Ismael S, Silvestre M, Vasques, M Araújo, J Morais J, Duarte MI, Pestana D, Faria A, Pereira-Leal J, Vaz J., Ribeiro P, Teixeira D, Marques C, Calhau C. A Pilot Study on the Metabolic Impact of Mediterranean Diet in Type 2 Diabetes: Is Gut Microbiota the Key? Nutrients, 2021, 13, 1228.

Oliveira H, Rodrigues C, Santos A, Veigas B, Faria A, Calhau C, de Freitas V, Baptista P, Mateus N, Fernandes A,  Fernandes I, GLUT1 and GLUT3 involvement in anthocyanin gastric transport- Nanobased targeted approach. Scientific Reports, 2019, 9:789

Marques C,  Fernandes I, Meireles M, Faria A, Spencer J,  Mateus N,  Calhau C. Gut microbiota modulation accounts for the neuroprotective properties of anthocyanins. Scientific Reports, 2018, 8, 11341.

Fernandes I, Marques C, Évora A, Cruz L, de Freitas V, Calhau C, Faria A, Mateus N. Pharmacokinetics of table and Port red wine anthocyanins: a crossover trial in healthy men. Food & Function, 2017, 8, 2030-2037.

Marques C, Fernandes I, Norberto S, Sá C, Teixeira D, de Freitas V, Mateus N, Calhau C, Faria A. Pharmacokinetics of blackberry anthocyanins consumed with or without ethanol: a randomized and crossover trial. Molecular Nutrition and Food Research, 2016, 60, 11, 2319-2330.

Meireles M, Rodríguez-Alcalá L, Marques C, Norberto S,  Freitas J,  Fernandes I, Mateus N, Gomes A, Faria A, Calhau C. “Effect of chronic consumption of blackberry extract on high-fat induced obesity in rats and its correlation with metabolic and brain outcomes. Food & Function, 2016, 20, 7, 1, 127-139.

Faria A, Fernandes I, Norberto S, Mateus N, Calhau C Interplay between anthocyanins and gut microbiota, Journal of Agricultural and Food Chemistry, 2014, 62,29, 6898-902.

Faria A, Meireles M, Fernandes I, C Santos-Buelga, Gonzalez-Manzano S, Dueñas M, de Freitas V, Mateus N, Calhau C. Flavonoid metabolites transport across a human BBB model. Food Chemistry, 2014, 149,190-196.

Faria A, Pestana D, Teixeira D, Couraud PO, Romero I, Weksler B, de Freitas V, Mateus N, Calhau C. Insights into the putative catechin and epicatechin transport across Blood-Brain Barrier; Food & Function, (2011), 2, 1, 39-44.

Faria A, Pestana D, Teixeira D, Azevedo J, de Freita Vs, Mateus N, Calhau C. Flavonoid transport across RBE4 cells: a blood-brain barrier model” Cellular & Molecular Biology Letters, 2010, 15, 2, 234-241. 

Faria A, Pestana D, Azevedo J, Martel F, de Freitas V, Azevedo I, Mateus N, Calhau C. Absorption of anthocyanins through intestinal epithelial cells – putative involvement of GLUT2. Mol Nutr Food Res, 2009, 53, 11, 1430-1437.

Faria A, Monteiro R, Pestana D, de Freitas, Mateus N, Azevedo I, Calhau C. Intestinal oxidative state can alter nutrient and drug bioavailability. Oxid Med Cell Long, 2009, 2, 5, 322-327.

  • 2020 - Bolsa Nacional Biocodex- Biocodex Microbiota Foundation
    MicroSpA & MicroRA: The role of microbiome on biological therapy efficacy in axial Spondyloarthritis and Rheumatoid Arthritis - a new paradigm”
  • 2019 - Bolsa Emílio Peres – SPD “MEDBIOME: Efeito da dieta mediterrânea no microbiata de diabéticos tipo 2”
  • 2018 - Bolsa Emílio Peres - SPD “Estudo aleatório do efeito da cerveja sem álcool no controlo glicémico de diabéticos tipo 2.”
  • 2017 - Bolsa Milupa Sociedade Portuguesa de Neonatologia DN-EL 2017
     “Avaliação da influência do tipo de alimentação em bebés prematuros no microbiota”
  • 2011 - 1ª Menção Honrosa dos Nutrition Awards 2011 Investigação em Ciências da Nutrição- APN e Grupo GCI. “Polifenóis – Os nutracêuticos do vinho tinto: biodisponibilidade e propriedades biológicas.”
  • 2010 - Finalista dos Nutrition Awards 2010 Investigação em Ciências da Nutrição - Associação Portuguesa de Nutricionistas e Grupo GCI  “Transporte transmembranar de flavan-3-óis na Barreira Hemo-Encefálica (BHE)”
  • Professor Doutor Nuno Mateus, Doutora Iva Fernandes e Doutor Helder Oliveira LAQV/REQUIMTE – Faculdade de Ciências da Universidade do Porto
  • Professora Doutora Maria Augusta Vieira-Coelho e Doutor Eduardo Moura Unidade de Farmacologia e Terapêutica – Dept. Biomedicina Faculdade de Medicina Universidade do Porto
  • Professoras Fátima Martel e Rita Negrão - Unidade de Bioquímica – Dept. Biomedicina Faculdade de Medicina Universidade do Porto
  • Professora Doutora Manuela Pintado - Escola Superior de Biotecnologia Universidade Católica Portuguesa
  • Doutor Christophe Espírito-Santo e Doutora Inês Brandão - Centro de Apoio Tecnológico Agro-Alimentar de Castelo Branco
  • Professor Pierre Olivier-Courad e Babette Weksler - Université Paris Descartes (INSERM) U1016
  • Professora Gabriela Macedo e Professora Juliana Macedo - UNICAMP
  • Professor Celestino Santos-Buelga- University of Salamanca
  • Professor Jeremy Spencer - University of Reading

Investigador Principal


Conceição Calhau
Cláudia Marques
André Rosário
João Araújo
Invited Assistant Professor
Inês Barreiros Mota
Juliana Morais
PhD student
Shámila Ismael
PhD student