Molecular Nutrition and Health

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Cláudia N. Santos

Principal Investigator
PhD in Plant Biochemistry and Regulation, Faculty of Sciences, University of Lisbon
Degree in Biochemistry, Faculty of Sciences, University of Lisbon

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Location:

CEDOC
Campus Sant'Ana
Pólo de Investigação, NMS, UNL
Rua Câmara Pestana, nº 6
Lab 1.7
1150-082 Lisboa, Portugal

Phone: (+351) 218 803 101
Fax: (+351) 218 851 920
E-mail: claudia.nunes.santos(at)nms.unl.pt

Research Interests:

Human nutritional biochemistry focusing on nutrients/bioactives components and its derivatives, their metabolism, physiological processes and the molecular mechanisms behind their effects on health and disease. Our approaches combine metabolism and nutritional mechanistic studies in humans, animals and relevant cellular models and organisms. The main cellular pathways associated with proteostasis including autophagy, ubiquitin/proteasome, and the unfolded protein response pathways are the focus. Overall we aim to understand the nutrition-related mechanisms of cellular processes at the molecular level and associated to lifestyle-related chronic illnesses.

In particular we are interested in:

I) The study of polyphenol metabolism in humans and animal models by metabolomics approaches: bioaccessability (in vitro digestion), bioavailability, kinetics parameters (human intervention studies), brain permeability and cellular metabolism;

II) Polyphenol metabolites bioactivity towards:
• Neurodegenerative diseases, focusing on Parkinson’s disease, neurodegeneration, neuroinflammation and blood brain barrier permeability
• Cardiovascular diseases, particularly associated with hypertension related dysfunctions
• Diabetes, particularly associated with IAPP (amylin) pathophysiology

Mechanistic studies are performed using yeast, relevant cell models of disease and animals, and state-of-art cellular and molecular approaches to unravel the molecular mechanisms of cytoprotection mediated by polyphenol-derived metabolites.

Discover more about the Molecular Nutrition and Health Lab

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NUTRITION AS A MEANS OF PREVENTING NEURODEGENERATIVE DISEASES

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A Nutrição como meio de prevenção das doenças neurodegenerativas

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Demência: como escolher os alimentos certos pode ajudar a retardar a destruição dos neurónios

INTERNATIONAL PROJECTS

1. ERC-2018-Starting grant with project LIMBo (N° 804229) PI- Cláudia N Santos. (ongoing)
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2. EU project CHIC “Chicory as a multipurpose crop for dietary fibre and medicinal terpenes”. (H2020, Call BIOTEC07-2017 New Plant Breeding Techniques (NPBT) in molecular farming: Multipurpose crops for industrial bioproducts). (ongoing)
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3. BacHBerry “BACterial Hosts for production of Bioactive phenolics from bERRY fruits”. (BacHBerry FP7-KBBE- 2013-613793).
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4. EUBerry: “The sustainable improvement of European berry production, quality and nutritional value in a changing environment”. (EUBerry FP7-KBBE-2010-265942).

NATIONAL PROJECTS

1. Therapeutics@DIAPP_Perceiving Diabetes as an Islet Amyloid PolyPeptide oligomeropathy: disease progression and therapeutic focus. PTDC/BIA-MOL31104/2017. PI – Regina Menezes

2. TherDIAPP_Islet Amyloid Polypeptide oligomers as critical entities in diabetes: early diagnosis and therapeutic focus. UID/Multi/04462/2013-SubProj Inova4health 44.
PI – Regina Menezes

3. CardioBDP- Mechanisms of Cardioprotection by Berries-driven Polyphenols, FCT-ANR/BEX-BCM/0001/2013 ANR. PI – Cláudia N Santos

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4. Fundo EDP para a Biodiversidade 2010/2012: ”Conservation and Recovery of Threatened endemic Flora in Portugal”. PI – Cláudia N Santos

5. Polyphenols as protective agents in cellular models of alpha-synucleinopaties, in particular Parkinson’s disease, PTDC/BIA-BCM/111617/2009. PI-Ricardo Boavida Ferreira and Co-PI-Cláudia N Santos

Selected Publications:

Bioacessibility and bioavailability

  • Tavares L, Figueira I, Macedo D, McDougall GJ, Leitão, MC, Vieira HLA, Stewart D, Alves PM, Ferreira RB, Santos CN, 2012, Neuroprotective effect of blackberry (Rubus sp.) polyphenols is potentiated after simulated gastrointestinal digestion. Food Chem 13: 1443-52
  • Pimpão R, Kraut N, Dew T, McDougall GJ, Stewart D, Ferreira RB, Santos CN, Williamson G, 2014, Urinary metabolite profiling identifies novel colonic metabolites and conjugates of phenolics in healthy volunteers. Mol Nutr Food Res 58: 1414–25
  • Pimpão RC, Ventura R, Ferreira RB, Williamson G, Santos CN, 2015, Phenolic-sulfates as new and highly abundant metabolites in human plasma after ingestion of a mixed berry fruit puree. Br J Nutr 113: 454-63
  • Garcia G, Nanni S, Figueira I, Ivanov I, McDougall GJ, Stewart D, Ferreira RB, Pinto P, Silva RFM, Brites D, Santos CN, 2017, Bioaccessible (poly)phenol metabolites from raspberry protect neural cells from oxidative stress and attenuate microglia activation. Food Chem 215: 274-83
  • André Brodkorb, Lotti Egger, Marie Alminger, Paula Alvito, Ricardo Assunção, Simon Ballance, Torsten Bohn, Claire Bourlieu-Lacanal, Rachel Boutrou, Frédéric Carrière, Alfonso Clemente, Milena Corredic, Didier Dupont, Claire Dufour, Cathrina Edwards, Matt Golding, Sibel Karakaya, Bente Kirkhus, Steven Le Feunteun, Uri Lesmes, Adam Macierzanka, Alan Mackie, Carla Martins, Sebastien Marze, David McClements, Olivia Menard, Mans Minekus, Reto Portmann, Claudia Santos, Isabelle Souchon, R. Paul Singh, Gerd Vegarud, Martin Wickham, Werner Weitschies, and Isidra Recio (2019), INFOGEST static in vitro simulation of gastrointestinal food digestion, Nature protocols, in press

Chemical and bioactivity profiling

  • Pimpão RC, Dew T, Oliveira PB, Williamson G, Ferreira RB, Santos CN, 2013, Analysis of phenolic compounds in Portuguese wild and commercial berries after multi-enzyme hydrolysis. J Agric Food Chem 61: 4053–62
  • Jardim,C, Macedo,D, Figueira, I, Dobson,G, McDougall, G, Stewart,D., Ferreira, RN, Menezes, R., Santos, CN, 2017, (Poly)phenol metabolites from Arbutus unedo leaves protect yeast from oxidative injury by activation of antioxidant and protein clearance pathways, Journal of Functional Foods, 32, 333-346, http://dx.doi.org/10.1016/j.jff.2017.03.010.
  • Almeida, AF, Santos, CN, Ventura, MR, 2017, Synthesis of New Sulfated and Glucuronated Metabolites of Dietary Phenolic Compounds Identified in Human Biological Samples, Journal of Agricultural and Food Chemistry, DOI: 10.1021/acs.jafc.6b05629
  • Kallscheuer, N., Menezes, R., Foito, A., Henriques da Silva, M. D., Braga, A., Dekker, W., Mendez Sevillano, D., Rosado-Ramos, R., Jardim, C., Oliveira, J., Ferreira, P., Rocha, I., Silva, A. R., Sousa, M., Allwood, J. W., Bott, M., Faria, N., Stewart, D., Ottens, M., Naesby, M., Santos, C. N. and Marienhagen, J. (2018) Identification and microbial production of the raspberry phenol salidroside that is active against Huntington's disease. Plant Physiology, doi: 10.1104/pp.18.01074.

Cellular mechanisms

  • Tavares L, Figueira I, McDougall GJ, Vieira HLA, Stewart D, Alves PM, Ferreira RB, Santos CN, 2013, Neuroprotective effects of digested polyphenols from wild blackberry species. Eur J Nutr 52: 225-36
  • Macedo D, Tavares L, McDougall GJ, Vicente Miranda H, Stewart D, Ferreira RB, Tenreiro S, Outeiro TF, Santos CN, 2015, (Poly)phenols protect from alpha-synuclein toxicity by reducing oxidative stress and promoting autophagy. Hum Mol Genet 24: 1717-32
  • Menezes R, Tenreiro S, Macedo D, Santos CN & Outeiro TF. From the baker to the bedside: yeast models of Parkinson's disease. Microbial Cell (2015), 2(8): 262-279. doi: 10.15698/mic2015.08.219.
  • Garcia G, Nanni S, Figueira I, Ivanov I, McDougall GJ, Stewart D, Ferreira RB, Pinto P, Silva RFM, Brites D, Santos CN, 2017, Bioaccessible (poly)phenol metabolites from raspberry protect neural cells from oxidative stress and attenuate microglia activation. Food Chem 215: 274-83
  • Macedo, D., Jardim, C., Figueira, I., Almeida, A. F., McDougall, G. J., Stewart, D., Yuste, J. E., Tomás-Barberán, F. A., Tenreiro, S., Outeiro, T. F., and Santos, C. N. (2018) (Poly)phenol-digested metabolites modulate alpha-synuclein toxicity by regulating proteostasis. Scientific Reports 8, 6965.
  • MCL de las Hazas, J Godinho-Pereira, A Macià, AF Almeida, MR Ventura,M-J Motilva, Santos C.N. (2018), Brain uptake of hydroxytyrosol and its main circulating metabolites: Protective potential in neuronal cells, Journal of Functional Foods 46, 110-117.
  • Rosado-Ramos R, Godinho-Pereira F, Figueira I, Jardim C, Garcia G, Menezes R. Exploring the Benefits of Cellular Models to Uncover Bioactive Polyphenols for Neurodegeneration. Curr Pharm Design (2018), 24:1-31. doi: 10.2174/1381612824666180629112148.
  • Menezes R, Rodriguez-Mateos A, et al. Impact of Flavonols on Cardiometabolic Biomarkers: A Meta-Analysis of Randomized Controlled Human Trials to Explore the Role of Inter-Individual Variability. Nutrients (2017), 9(2). pii: E117. doi: 10.3390/nu9020117.
  • Figueira, I; Garcia, G; Pimpão, RC; Terrasso;AP; Costa, I.; Almeida, AF; Tavares; L; Pais, TF; Pinto, P; Ventura, MR; Filipe, A; McDougall, G; Stewart, D; Kim, KS; Palmela, I; Brites, D; Brito, MA; Brito, C; Santos, CN, (2017), Polyphenols journey through blood-brain barrier towards neuronal protection, Scientific Reports, doi:10.1038/s41598-017-11512-6.
  • Figueira, I., Tavares, L., Jardim, C., Costa, I., Terrasso, A. P., Almeida, A. F., Govers, C., Mes, J. J., Gardner, R., Becker, J. D., McDougall, G. J., Stewart, D., Filipe, A., Kim, K. S., Brites, D., Brito, C., Brito, M. A., and Santos, C. N. (2017) Blood–brain barrier transport and neuroprotective potential of blackberry-digested polyphenols: an in vitro study. European journal of nutrition, https://doi.org/10.1007/s00394-017-1576-y.

Memberships of Scientific Societies and Boards of European Networks

2017-current: Management Committee of Action COST-NutRedOx- Personalized Nutrition in aging society: redox control of major age-related diseases

2016-current: Management Committee of Action COST- TRANSAUTHOPHAGY- European Network of Multidisciplinary Research and Translation of Autophagy knowledge

2014-2018: Management Committee of Action COST-POSITIVe- Interindividual variation in response to consumption of plant food bioactives and determinants involved.

2014-2018: Management Committee of Action COST- PROTEOSTASIS- European network to integrate research on intracellular proteolysis pathways in health and disease

2011-current: Member of EPSO Crops, Food and Health working group

2011-2014: Management Committee of Action COST-INFOGEST- Improving health properties of food by sharing our knowledge on the digestive process

2007-2010: Member of Action COST-Euroberry.

Prizes and Awards

• Fulbright Research Fellowship for an internship at University of Kentucky, College of Medicine, Lexington, EUA, 2019 (Ana Filipa Raimundo)

AFR

• Nuno Castelo Branco Prize of Sociedade Portuguesa de Diabetologia (Portuguese Diabetes Society) for the project "Therapeutics4DM: Towards the elucidation of Islet Amyloid Peptide role in Diabetes Mellitus – opening new venues for therapeutic intervention", 2016
Project Leaders: Regina Menezes (iBET and ITQB-NOVA); Rogério Ribeiro (CEDOC and APDP)

• Nutrition Awards, Research and Development - 2º Honorable mention, Project: Portuguese wild blackberries, new functional foods for the brain. 2012
Project Leaders: Lucélia Tavares; Cláudia Santos - Instituto de Tecnologia Química e Biológica (ITQB)

Team photos

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LIMBo - Zooming the link between diet and brain health: how phenolic metabolites modulate brain inflammation

Team Members

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Objective

Currently a big concern of our aging society is to efficiently delay the onset of neurodegenerative diseases which are progressively rising in incidence. The paradigm that a diet rich in the phenolics, prevalent e.g. in fruits, is beneficial to brain health has reached the public. However their mechanistic actions in brain functions remain to be seen, particularly since the nature of those acting in the brain remains overlooked. I wish to address this gap by identifying candidate compounds that can support development of effective strategies to delay neurodegeneration.

Specifically, I will be analysing the potential of dietary phenolics in both prevention and treatment (i.e delay) of neuroinflammation – key process shared in neurodegenerative diseases. To break down the current indeterminate status of “cause vs effect”, my vision is to focus my research on metabolites derived from dietary phenolics that reach the brain. I will be investigating their effects in both established and unknown response pathways of microglia cells - the innate immune cells of the central nervous system, either alone or when communicating with other brain cells. Ultimately, to attain an integrated view of their effects I will establish nutrition trials in mice. LIMBo considers both pro- and anti- inflammatory processes to preliminary validate the action of any promising metabolite in prevention and/or therapeutics.

LIMBo provides valuable scientific insights for future implementation of healthy brain diets. My group is in a unique position to address LIMBo objectives due to multidisciplinary expertise in organic synthesis, metabolomics and molecular and cellular biology, together with our previous data on novel neuroactive metabolites.

LIMBo also creates far-reaching opportunities by generating knowledge that impacts our fundamental understanding on the diversity of phenolic metabolites and their specific influences in neuroinflammation and potential use as prodrugs.

Grant agreement ID: 804229

Funded under H2020-EU.1.1.

Publications
  • Diogo Carregosa, Rafael Carecho, Inês Figueira, and Cláudia N Santos, Low-Molecular Weight Metabolites from Polyphenols as Effectors for Attenuating Neuroinflammation, 2019. Journal of Agricultural and Food Chemistry. DOI: 10.1021/acs.jafc.9b02155

Check ou latest work

• Does our brain uptake gut (poly)phenols metabolites? Watch our video! Thanks for the support @ERC_Research and @COSTNutRedOx!!!

• Have you looked at our review? We discuss circulating low molecular weight metabolites resulting from polyphenol metabolism by the #microbiota and liver, and how these molecules could affect the brain by modulating inflammation on #microglia! #CEDOC @ERC_Research

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