Project description:Dysbiosis of the gut microbiota has been linked to disease pathogenesis in type 1 diabetes (T1D), yet the functional consequences to the host of this dysbiosis is unknown. Here, we have performed a metaproteomic analysis of 103 stool samples from subjects that either had recent-onset T1D, were high-risk autoantibody positive or low-risk autoantibody negative relatives of individuals with beta cell autoimmunity or healthy individuals to identify signatures in host and microbial proteins associated with disease risk. Multivariate modelling analysis demonstrated that both human host proteins and microbial derived proteins could be used to differentiate new-onset and seropositive individuals from low-risk and healthy controls. Significant alterations were identified between subjects with T1D or islet autoimmunity versus autoantibody negative and control subjects in the prevalence of individual host proteins associated with exocrine pancreas function, inflammation and mucosal function. Data integrationIntegrative analysis combining the metaproteomic data with bacterial abundance showed that taxa that were depleted in new-onset T1D patients were positively associated with host proteins involved in maintaining function of the mucous barrier, microvilli adhesion and exocrine pancreas. These data support the notion that T1D patients have increased intestinal inflammation and decreased barrier function. They also confirmed that pancreatic exocrine dysfunction occurs in new-onset T1D patients and show for the first time 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.
Project description:The human gut microbiota plays a vital role in host health by acting as a barrier against pathogens, boosting the immune system, and metabolizing complex carbon sources into beneficial compounds such as short-chain fatty acids (SCFAs). However, external factors like diet and xenobiotics, including food colorants, can impact this microbial community. Brilliant blue FCF (E-133), a common food dye that is not absorbed or metabolized by the body, thus, leading to significant exposure of the gut microbiota, and its effects on it are not well-documented. This study investigated the impact of brilliant blue on the simplified human gut microbiota model (SIHUMIx) over a seven-day exposure period, followed by a four-day recovery phase. Using continuous culture bioreactors along with metaproteomic and metabolomic analyses, the research uncovered substantial structural and functional changes in the microbiota. Our findings showed alterations in the species abundance such as B. thetaiotaomicron, B. longum, and C. butyricum, reductions in energy metabolism by-products, particularly lactate and butyrate, and disruptions in metabolic pathways involved in the metabolism of xenobiotics and amino acids. The results indicate that brilliant blue exposure compromises microbiota stability and functionality, highlighting the need for further research on its long-term effects and recovery mechanisms. This study underscores the importance of assessing the impacts of food additives on gut microbiota as part of comprehensive health risk evaluations.