JV (Josep) Rubert Bassedas PhD

josep.rubert@wur.nl

Microbial Metabolites: Driving Forces Behind Gut Resilience

Vision: I envision enhancing the intestine's resilience. To achieve this, I plan to use food as a substrate, utilize gut microbes as biofactories, and focus on microbial metabolites, which are key players in regulating intestinal epithelial cell responses. By advancing our understanding of the food-gut microbiome-intestine triangle, I aim to predict the combinations of foods needed to generate a unique chemical fingerprint of microbial metabolites that positively influence intestinal resilience.

Our diet is a complex mixture of macromolecules. After being digested, nutrients are absorbed by absorptive cells, and gut microbes utilize undigested food to keep them alive and generate microbial metabolites. The gut microbiome produces a diverse metabolite repertoire by breaking down dietary products and endogenously synthesizing essential cofactors. Only a limited number of microbial metabolites derived from carbohydrates, lipids, and proteins have been reported and demonstrated to influence intestinal health through various signaling pathways. However, many microbial metabolites have not yet been characterized, and their biological role remains unexplored.

Current research linking diets and gut health relies heavily on observational studies and correlations, leaving a significant gap in our understanding of the biological mechanisms involved. Therefore, it is essential to understand how dietary factors modulate the gut microbiome to produce microbial metabolites. My ambition is to decode how the food escaping digestion drives microbial communities to release a pattern of metabolites that make the intestine resilient and, in turn, prevent chronic intestinal inflammation and barrier dysfunction.

My research aims to reveal the pivotal role of microbial metabolites in regulating intestinal resilience.

This interdisciplinary research is geared towards three specific objectives that, combined, will contribute to the realization of my overall vision:

1. To identify the role of dietary factors (food particle size, macronutrients, phytochemicals, and food processing) in modulating the production of microbial metabolites.
2. To elucidate the biological mechanisms by which microbial metabolites influence intestinal resilience.
3. To develop novel foods and dietary strategies targeting the determinants driving intestinal resilience.

My approach is to combine in vitro and in vivo models to translate this research vision into a reality.

During my scientific career, I have developed a robust foundation in targeted and untargeted metabolomics, which has been instrumental in identifying and (semi)quantifying metabolites in various biological fluids. My initial focus will be on leveraging my metabolomics expertise to develop a comprehensive atlas of microbial metabolites. Secondly, I intend to clarify the biological roles of microbial metabolites in enhancing intestinal resilience by utilizing 2D intestinal organoid models along with multi-omics approaches.