Emmy Noether Group for Computational Microbiome Research

Research

Our aim is to understand the role of the human microbiome in health and to identify aberrant host-microbial interactions in immune-related diseases. Ultimately, we want to leverage this knowledge to improve our ability to diagnose, treat and prevent these diseases with new microbiome-based approaches, which aim at restoring the host-microbial balance.

The human microbiome is the large collection of bacteria, viruses, archaea and fungi that live in and on our body. Most of these organisms live in our gut and provide important immunological and metabolic benefits. In many diseases, such as chronic inflammatory bowel diseases and immune-related diseases, an imbalance of these microbial communities has been observed. The underlying reasons and consequences of this imbalance are largely unknown though. Previous studies have identified taxonomic changes of the microbiome and disease-associated bacterial species. However, different strains of the same species can substantially differ in their functional capacities. To address these challenges, my lab uses integrated analyses of complex multi-omics datasets from large clinical cohorts to computationally predict host-microbial interactions. We then follow up with experimental validation of the immunogenicity and inflammatory activity of the identified bacterial strains and metabolites, providing insights into the potential mechanisms of the human microbiome in health and diseases.

The role of the oral microbiome in the pathogenesis of gastrointestinal diseases (Emmy Noether Project)

While oral bacteria rarely colonize healthy intestines, they are found in the gut microbiome in connection with several diseases, including IBD, 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 investigate strain-specific differences of bacteria in oral and gut samples from patients with IBD and liver cirrhosis. This includes comparing gene expression and metabolic activity of oral versus gut strains, identifying disease-associated metabolites in connection with these strains and establishing their colitogenic potential to provide evidence of a causal role

HEROINE: Hormone-microbiome interactions as a key-player in female health (ERC Starting Grant)

Incidence rates of inflammatory and autoimmune diseases are increasing dramatically and are often higher in women. Hormones are hypothesized to play a central role in this sex bias. At the same time, the microbes that live in and on our body are often linked to disease pathology. Microbes are capable of producing hormone-like signals, can metabolize hormones and regulate their production, while hormones can influence bacterial growth. However, a key understudied aspect is the interplay between hormones and microbes in the human body and the role of these interactions in human health and disease. We are investigating hormone-microbiome interactions as a key player in female health, including their role in infertility and the possibility of using microbiome-based therapeutic strategies to treat these disorders.

Impact of Desulfovibrio spp. and sulfur metabolism on the pathogenesis of chronic intestinal inflammation and colitis-associated cancer (CRC 1371)

Desulfovibrio spp. in the human digestive tract can use sulfate to create hydrogen sulfide (H2S). While endogenous H2S is an important signal transducer in human cells, elevated exposure may induce aberrant tissue responses, including oxidative stress, genotoxicity and loss of epithelial barrier integrity. In this project, we are addressing the causal role of Desulfovibrio and their sulfur metabolism in the pathogenesis of colitis and colitis-associated cancer.

Funders

We would like to thank all of our funders for their continuing support!