Impact of strain-level functional diversity in mucin-degrading bacteria on the pathogenesis of inflammatory bowel disease

Descripción del proyecto

Factores del microbioma intestinal que influyen en la enfermedad inflamatoria intestinal

La microbiota intestinal está formada por billones de microorganismos, entre los que se incluyen bacterias, virus y hongos. Desempeña un papel fundamental en la salud humana, ya que facilita la digestión, protege contra los organismos patógenos y contribuye al funcionamiento del sistema inmunitario. Se ha relacionado la alteración de esta comunidad microbiana con la enfermedad inflamatoria intestinal (EII). Sin embargo, aún no se han identificado los microorganismos concretos responsables de provocar la enfermedad. El equipo del proyecto STRAINGUT, que cuenta con el apoyo de las Acciones Marie Skłodowska-Curie, se centra en «Ruminococcus gnavus», una bacteria intestinal que se asocia con frecuencia a la EII, pero que está presente en alrededor del 90 % de las personas sanas. Los investigadores analizarán cincuenta cepas de esta bacteria para identificar las funciones específicas de cada cepa que favorecen la inflamación. Los resultados del proyecto permitirán comprender los mecanismos que rigen las interacciones entre el hospedador y la microbiota y contribuirán a la creación de nuevas estrategias para la prevención de la EII en las personas con riesgo de padecerla.

Objetivo

Recent advances in microbiome research have revealed numerous associations between gut bacteria and host health. However, these correlations do not establish causality and provide limited insight into the mechanisms by which specific bacteria influence disease. There is therefore a critical need to uncover underlying bacterial functions through targeted studies. This project focuses on inflammatory bowel disease (IBD), a condition marked by chronic intestinal inflammation and disruption of the colonic mucus barrier. Among bacteria linked to IBD are mucin-degraders, which can feed on components of the mucus layer and promote inflammation in gnotobiotic models. One such bacterium, Ruminococcus gnavus, is consistently associated with IBD. Yet its role remains poorly understood, as it is also highly prevalent in the healthy European population (~90%), suggesting that mere presence is not sufficient to drive inflammation. Recent studies and preliminary work from the host lab show that R. gnavus displays substantial genetic and functional diversity across strains, indicating that its pro-inflammatory potential may be strain-dependent and shaped by distinct functional traits. The STRAINGUT project aims to exploit this variability to identify strain-specific functions of R. gnavus that promote inflammation. To this end, a collection of 50 R. gnavus strains will be functionally screened in vitro, followed by in vivo validation of candidate strains in a gnotobiotic model of IBD. This approach will enable the identification of functional markers—which may include specific mucin-degradation processes—that modulate colitis. Their translational relevance will then be assessed using ex vivo human samples and IBD metagenomic datasets. By pinpointing key R. gnavus functions involved in inflammation, STRAINGUT promises to deliver novel mechanistic insights into host–microbiota interactions in IBD and pave the way for innovative strategies to prevent disease in at-risk individuals.