Final Report Summary - MICROBESINSIDE (Exploitation of Our Intestinal Microbiota)
This ERC project MicrobesInside effectively run at two locations, University of Helsinki and Wageningen University (coordinator). In the project we have unraveled the molecular mechanisms by which two industrially important and relevant intestinal commensals interact with the human host at the mucosal interface: Lactobacillus rhamnosus GG, worlds' best studied probiotic and Akkermansia muciniphila, an unique anaerobic intestinal commensal that exclusively grows on the mucus we provide it with.
We discovered that administration of Akkermansia muciniphila increases the mucosal barrier in mouse and human model systems. Of great significance was the finding that administration of A.muciniphila protects against high fat induced obesity. Finally, we isolated new Akkermansia strains and species and used comparative and functional genomics approaches to unravel their metabolic pathways. This all opens the way for further and rationally development of Akkermansia in next generation microbial therapies.
Lactobacilus rhamnosus GG is globally used as a probiotic but its mode of action is unknown. We have identified the extracellular pili that are decorated by the mucus-binding SpaC protein as the relevant ligand in immune signaling and host interaction. The biogenesis of the pili was studied by reverse and forward genetics, revealing critical residues in SpaC and its dedicated sortase. Finally, a non-GMO strategy in combination with next gen resequencing was used to generate food-grade derivatives that do not produce pili. These have been used in a human intervention trial revealing the importance of the SpaC-decorated pili in persistence. These and other food-grade strains are now being used in further human experiments aimed at further understanding probiotic functionality.
We discovered that administration of Akkermansia muciniphila increases the mucosal barrier in mouse and human model systems. Of great significance was the finding that administration of A.muciniphila protects against high fat induced obesity. Finally, we isolated new Akkermansia strains and species and used comparative and functional genomics approaches to unravel their metabolic pathways. This all opens the way for further and rationally development of Akkermansia in next generation microbial therapies.
Lactobacilus rhamnosus GG is globally used as a probiotic but its mode of action is unknown. We have identified the extracellular pili that are decorated by the mucus-binding SpaC protein as the relevant ligand in immune signaling and host interaction. The biogenesis of the pili was studied by reverse and forward genetics, revealing critical residues in SpaC and its dedicated sortase. Finally, a non-GMO strategy in combination with next gen resequencing was used to generate food-grade derivatives that do not produce pili. These have been used in a human intervention trial revealing the importance of the SpaC-decorated pili in persistence. These and other food-grade strains are now being used in further human experiments aimed at further understanding probiotic functionality.