IMIB - Institute for Molecular Infection Biology

Establishment of a human primary 3D model for colonization with anaerobic gut bacteria

The large intestine plays a crucial role in nutrient absorption, water transport, and maintenance of the intestinal microbiota. Bacteroides thetaiotaomicron is an abundant and prevalent symbiotic member of the intestinal microbiota in humans and plays an important role in the digestion of dietary-derived, complex polysaccharides and in conferring colonization resistance against enteric infections. While this obligate anaerobic commensal can routinely be grown in vitro in rich or defined minimal media, in-vivo models for the co-cultivation of B. thetaiotaomicron with human cells are sparse and limited in terms of their reflection of the true in-vivo niche. The aim of my project is to establish a human tissue model for B. thetaiotaomicron colonization that mimics several aspects of the in-vivo situation, including a hypoxic milieu, three-dimensional crypt structures of the gut epithelium, and production of a mucus layer. To accomplish this, I will use human derived primary colon cells to establish an organoid culture and subsequently seed them on a biological scaffold. Once established, the Bacteroides pre-colonized in-vitro model may then be infected with facultative or obligate anaerobic pathogens to identify novel mechanisms of host-microbiota-pathogen interactions in the human gut.