C. Santos Lab | How can metabolites from gut microbiota affect neurodegenerative diseases?

Did you know that our gut has microorganisms that produces metabolites of high importance to human health, including neurodegenerative diseases?



Cláudia N. Santos and Diogo Carregosa

That is what is discussed in the literature review performed by Cláudia N. Santos lab, Molecular Nutrition and Health, including PhD student Diogo Carregosa as first author of this publication from Nutrients journal. It was also a joint effort with the Rita Teodoro and António Jacinto labs at CEDOC-NMS, showing the strength of collaboration at our institute and highlighting the importance of the different animal models we use in our research.

We talked with them to know more:

What led you to prepare and publish this review?

The main reason why we were led to prepare this review was the realization that there was a major gap in the literature. In recent years the knowledge on gut microbiota has been growing. This group of microorganisms present in our gut have the ability to degrade molecules present in fruits and vegetables into different metabolites that will appear in human circulation and may have other important functions. This is particularly true for (poly)phenols, the natural organic compounds present in fruits and vegetables, that we approach in this review focusing in their gut low molecular weight (poly)phenol metabolites and their ability to modulate processes of neurodegeneration. These low molecular weight metabolites are described in circulation but knowledge for their potential health effects is lacking. Moreover the few data available is dispersed across several publications. As such, we decided to search and combine the information in our recently published review. We also noticed that due to the difficulties of working with human samples, the potential health effects of these circulating food-derived compounds in humans has been hardly tested. In that moment we decided to take advantage of one of the greatest strengths of our research institute CEDOC-NMS: the great diversity of researchers that work with different model organisms such as mice and rat, zebrafish, Drosophila and yeast and our ability to talk and collaborate. This review brings together researchers from Molecular Nutrition and Health Lab (Cláudia Nunes dos Santos lab), Neuronal Growth And Plasticity (Rita Teodoro Lab) and Tissue Repair And Inflammation (António Jacinto Lab). In the end, we were able to combine all the evidence present in the literature about these microbiota metabolites in different model organisms, while addressing these gaps of knowledge.

Why is this important? The reason this recently published review is important is to address what we know, and still do not know, about these (poly)phenols metabolites produced by the microbiota that are present in human blood. These molecules are in our body every day, especially when we eat fruits and vegetables, but we still do not fully understand what they do. This is particularly important because the low amount of information available shows that they might have brain protective effects. By compiling this information, we can have a stronger idea about their effects, identify what should still be done and make a stronger case for future research plans in consolidating this information and advancing to human research studies.

Can you use an analogy to help us understand this field? We now understand that vitamins like B and K are very dependent, not only on what we eat, but also on gut microbiota and how they make such vitamins bioavailable. Such vitamins are essential for the regular function of our organism. Like vitamins, the (poly)phenols metabolites presented in our review are highly dependable on gut microbiota for their production and increasing their concentration. However, by contrast with vitamins, our understanding of the potential health effects of these molecules in humans, presented in our review, is still rather low.

What questions remain to be asked in this field that your group will pursue? We have searched the literature for the potential brain health benefits of more than 100 (poly)phenols produced by gut microbiota, yet we only found information about less than 20 of these molecules. That means a lot of molecules remain unstudied. For the molecules that have been studied, we still require more evidence to fully advance to human research studies. Also we have understood that the model organisms here present in CEDOC have been useful to create some of this evidence and are powerful tools that could and should be used in the future to increase our knowledge about the brain health benefits of (poly)phenol metabolites. This work reveals that we at CEDOC are in a unique position, with complementary expertise, to make an important contribution to the future of our understanding of the molecular mechanism behind nutritionally relevant molecules.

You can find the full article at Nutrients, titled “Overview of Beneficial Effects of (Poly)phenol Metabolites in the Context of Neurodegenerative Diseases on Model Organisms”, here


Diets rich in (poly)phenols originate large amounts of flavonoids and flavonoid conjugates reaching the digestive system. (1) In the small intestine, epithelial and bacterial enzymes removesugar conjugates while absorption occurs. (2) The majority of flavonoids travel to the lower part of the gut where microbiota catabolizes flavonoids into LMWPM that will be absorbed into enterohepatic circulation. (3) LMWPM will enter systemic circulation intact or will undergo phase I and II metabolic reactions by intestinal and liver cells before reaching the circulation. LMWPM—low molecular weight (poly)phenol metabolites. L.I.—large intestine