Faecal metaproteomics reveals host-microbiota interactions in the pathogenesis of type 1 diabetes

Changes in the gut microbiota have been implicated in the pathogenesis of type 1 diabetes (T1D). The causes and functional consequences of an altered microbiota to the host immune response against the pancreas in T1D is unknown. We have performed a multi-omic integrative analyses of human stool samples to identify a T1D associated disease signatures linked to host proteins and gut microbial proteins and taxa. Using a meta-proteomic analysis of 101 stool samples from subjects with recent-onset T1D, islet autoimmunity (seropositive) and low-risk individuals we have identified significant changes in host proteins associated with inflammation, exocrine pancreas function and gut barrier function in individuals with new-onset T1D and high risk subjects with islet autoimmunity. Integration of the meta-proteomic data with bacterial abundance information identified specific microbial taxa correlated with these differentially abundant proteins. These data support the notion that T1D patients have increased intestinal inflammation and decreased barrier function and that these changes may be linked to disease progression. They also confirmed that pancreatic exocrine dysfunction occurs in new-onset T1D patients and show that this dysfunction is present in high-risk individuals prior to disease onset. Our data has identified a unique T1D-associated signature in stool that may be useful as a means to monitor disease progression or response to therapies aimed at restoring a healthy microbiota.