The role of the oral microbiome in the pathogenesis of gastrointestinal diseases

• Applicant: Dr. Melanie Schirmer
• Subject Area: Nutritional Sciences ; Bioinformatics and Theoretical Biology ; Gastroenterology
• Term: since 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 426120468

My research focuses on the human microbiome, the large collection of bacteria, viruses, archaea and fungi that live in and on our body, and its role in human health. There are as many microbial organisms in and on our body as there are human cells. Most of these organisms live in the gut and provide important immunological and metabolic benefits. Gut microbial imbalances (dysbiosis) are linked to aberrant immune responses in gastrointestinal (GI) diseases. For many of these diseases similar dysbiosis patterns are observed with a general decrease in microbial diversity and specific organisms or groups of organisms are enriched or depleted. Microbiome research to date has largely focused on taxonomic composition and the identification of differentially abundant microbes. However, mechanistic links between gut microbial dysbiosis and aberrant immune responses are largely missing, which greatly limits our ability to treat and prevent these diseases.We will answer these questions in the context of bacteria from the oral cavity and their role in GI diseases, such as inflammatory bowel disease (IBD) and Helicobacter pylori infections. Both diseases affect millions of people worldwide. While oral bacteria rarely colonize healthy intestines, they are found in the gut microbiome in connection with several diseases, including IBD, H. pylori infections, colorectal cancer and liver cirrhosis. In IBD, a striking increase of oral taxa in the gut is associated with disease severity, the requirement of colectomy and treatment efficacy. However, which role oral bacteria play in disease pathogenesis and why they are able to engraft in the gut of IBD patients is currently unknown. We will investigate strain-specific differences of bacteria in oral and gut samples from patients with IBD and H. pylori infections. This will include a comparison of gene expression and metabolic activity of oral versus gut strains, the identification of disease-associated metabolites in connection with these strains and establishing their colitogenic potential to provide evidence of a causal role. We will also investigate which role medication, such as antibiotics and proton-pump inhibitors, play in bacterial translocation by examining these treatments in the context of H. pylori infections. My research will result in crucial insights into the role of oral microbial strains in the pathogenesis of GI diseases and will provide fundamental knowledge about the functionality of the microbiome in IBD and H. pylori infections. This will constitute an important step towards understanding the underlying mechanisms between gut microbial dysbiosis and aberrant immune responses. While the human genome is fixed, the microbiome can be altered. My goal is to ultimately leverage this knowledge to improve our ability to diagnose, treat and prevent these immune-related diseases with new microbiome-based approaches, which aim at restoring the host-microbial balance in disease.

• DFG Programme: Independent Junior Research Groups