Mucus-microbiota interplay along the gut-lung-axis

In the B05 project, our primary objective has been and continues to be investigating the interdependence of microbiome, hydrogel properties and barrier integrity at mucosal surfaces throughout change as well as resilience. During the first funding period, our primary focus was the gut. So far, we 1) characterized the gut microbiota associated with disrupted mucosa in clinical samples and experimentally tested 2) mucosal impact of impaired microbial interaction capacity of the host through TLR5 deficiency as well as 3) mucosal impact of gut microbiome disruption through antibiotics. To efficiently collect and integrate this data we developed protocols for joint mucus-microbiome multi-omics phenotyping from human and animal samples, and computational tools for complex -omics data integration, relying on within-CRC clinical collaborations (B04|Siegmund/Weinhart) as well as proteomic and glycomic (C03|Pagel/Nouailles, Z01|Mertins/Ludwig/Pigaleva) platforms. We found both universal and condition-specific micro­biome correlates of mucosal disruption, so the next step is to verify causality and directionality of these associations. More important, acknowledging the bidirectional interaction between the gut and lung during mucosal disruption, it is essential to extend our inquiry to other clinically relevant mucosal surfaces, by exploring interactions within and between intestinal and airway mucosal surfaces.