Junior Research Group Microbiota–Host–Interaction

Head: Dr. Gunnar Loh

Interactions between gut bacteria and the host are implicated in both health and lifestyle associated diseases including cancer. We aim to identify such interactions between gut bacteria and the host that possibly contribute to the onset or perpetuation or to the prevention of these disorders.

Projects

Host-microbe interactions under chronic gut inflammation

Inflammatory bowel diseases (IBD) significantly affect quality of life and are associated with an elevated risk of developing colorectal cancer. The etiology of IBD is poorly understood. However, it is accepted that gut bacteria play an important role in these diseases. We study the role of gut bacteria in interleukin 10 deficient (IL-10-/-) mice which show chronic gut inflammation and a high incidence of colorectal carcinoma. We previously demonstrated in IL-10-/- mice that inflammation is associated with reduced intestinal microbiota diversity in conjunction with a bloom of only few species. To identify environmental factors that cause these changes, we measured intestinal cholesterol, coprostanol, and bile acids (BA) in colitic and healthy mice. Higher cholesterol and primary BA concentrations were detected in the inflamed gut. These elevated levels were associated with an increased abundance of BA-resistant bacteria in the colitic mice. Whether high colonic sterol concentrations can trigger gut inflammation and cancer formation remains to be elucidated.

Impact of bacterial lignan activation on breast cancer

Lignans are secondary plant metabolites with protective effects against hormone-dependent cancers. These effects depend on the bacterial transformation of the lignans to enterodiol and enterolactone. A lignan-transforming bacterial consortium composed of Clostridium saccharogumia, Blautia pro ducta, Eggerthella lenta, and Lactonifactor longoviformis has previously been characterized by the Department of Gastrointestinal Microbiology. We associated germ-free rats with this consortium, fed the animals a lignanrich diet and induced breast cancer. Germ-free rats served as control. Lignan activation was observed in the associated but not in the germ-free animals. The associated rats developed less and smaller tumors. The tumor cells displayed a lower proliferation (Fig. 1, Fig. 2 A) and a higher apoptosis (cell death) rate (Fig. 2 B). These findings clearly demonstrate that bacterial lignan transformation is crucial for the anti-cancer effects of these plant compounds.

Host-specific microbiota

The intestinal microbiota composition is host specific and stable over time. The genetic background of the host is thought to contribute to this phenomenon. To identify factors that might be involved in selecting a host-specific microbiota, we associated germ-free inbred mice with a C3H and a C57BL/10 background with gut bacteria from one single donor mouse. We observed a microbiota development that was specific for the respective mouse strain and concluded that genetic traits influence gut bacterial communities in our model. Using a transcriptomic approach, we measured mucosal gene expression in the colon of the experimental animals. Genes encoding components of the innate immune system were differentially expressed between the mouse groups. The expression differences of the toll like receptor (TLR) 1 and the cluster of differentiation (Cd) 14, which are involved in the recognition of bacterial cell wall constituents, as well as the antibacterial phospholipase A2, group IIA and angiogenin 4 were verified at the mRNA level. In future experiments, we will elucidate the role of antibacterial substances in regulating intestinal microbiota composition.