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10:15 Uhr
V-05:
System diagnostics of the human gut microbiome using metaproteome analysis of fecal samples.
Dr. Robert Heyer | OvGU, Magdeburg | Germany
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Dr. Robert Heyer | OvGU, Magdeburg | Germany
A multitude of diseases are considered to be correlated with a dysbiosis of the gut microbiome, e.g. inflammatory bowel disease (IBD), diabetes, autoimmune diseases or depression. Unfortunately, up to now, it is for most diseases unclear if the dysbiosis is a cause of the disease or a result. Nevertheless, patient treatment may benefit from in-depth microbiome characterization performed in addition to the commonly associated clinical laboratory analyses enabling a more precise diagnosis of the disease or a monitoring of the disease progression. Potentially, information about the gut microbiome might even help to predict the (in)compatibility of certain drugs, enabling a more personalized patient treatment.
Technical advance of the past 10 years concerning the development of high throughput methods for the identification of genes (metagenomics/metatranscriptomics), metabolites (metabolomics) and proteins (metaproteomics) allow now a fast and reliable description of the gut microbiome. Among these methods, metaproteomics has the particular advantage that it enables both the identification of proteins from the microorganisms and from the host. Whereas the former provides information about the taxonomic composition and the functionality of the microbiome, the latter supports to draw conclusions about the patient’s health.
In this presentation I will introduce a workflow for metaproteome analysis of fecal samples comprising cell lysis, protein extraction, tryptic digestion, LC-MS/MS measurement and bioinformatics data evaluation. Furthermore, I will talk about challenges and potentials of the application of fecal metaproteomics for clinical diagnosis. As examples I will present one study focusing on a weight loss program and one study including a larger cohort of patients with IBD (Ulcerative Colitis and Crohn’s disease).
Due to the decrease of weight and a diet rich in fibers an improvement of the health status of the gut was observed as indicated by a decrease in the abundance of proteins assigned to the UniProtKB keywords inflammation and immune response. Furthermore, the abundance of microbial proteins related to the degradation of complex polymers increased.
In the IBD study, we could show that in feces of IBD patients IgG and neutrophil extracellular traps were significantly increased and correlated with the clinical disease activity. Furthermore, several alterations of the abundance of microbial proteins were observed such as a decrease in the abundance of the transcriptional regulatory protein RprY from Bacteroides fragilis (UniRef50_Q9AE24), which might contribute to IBD pathogenesis.
In sum, fecal metaproteomics reveals information about the health of the host and its microbiome as well as improves our understanding of the complex relationships between the microbiome and pathogenesis of several diseases.