The role of primary metabolites in the intestinal ecosystem under normal and inflamed conditions

Ludwig-Maximilians-Universität München
Max von Pettenkofer-Institute for Hygiene and Clinical Microbiology

Prof. Dr. Barbara Stecher (P08)


The composition of the gastrointestinal microbiota is not only determined by stochastic processes such as dispersal or ecological drift, but is strongly influenced by deterministic interactions between species and the individual host environment. In the healthy gut, the enteric microbial community faces frequent changes in the availability of nutrients. The source of metabolites varies in space and time with dietary composition, as well as with host-dependent factors. Especially inflammatory processes can create metabolic niches in the gut that may affect the composition and function of the microbial ecosystem.

Therefore, in the dynamic chemical environment of the mammalian gut, antagonistic interactions, such as substrate competition, as well as beneficial interactions shape the composition of the enteric microbiota. A prime example for the latter is metabolic cross-feeding between individual species. Cross-feeding leads to formation of metabolic networks in the community, and increases metabolic output. As metabolic interactions occur between a multitude of species, creating heuristics to identify the nature and complexity of interactions based on phylogeny only is challenging. To understand and predict the assembly and function of complex microbial communities, a more mechanistic knowledge of metabolic interactions is needed.

In the current project, we will investigate the role of primary gut luminal metabolites, specifically short chain fatty acids and pyruvate, in a defined subset of community members and in gnotobiotic mouse models, as well as mouse models of gut inflammation, using growth and metabolome profiling approaches. By that, we aim to gain a better understanding of the spatial, temporal and compositional complexity of ecological and metabolic microbial community interactions in the mammalian gut. Most interestingly, especially pyruvate plays an important role in both prokaryotes and eukaryotes, as it not only forms the hub between aerobic and anaerobic metabolism, but further acts as scavenger for reactive oxygen species. Recently, a two-component system for pyruvate sensing and transport was discovered in the human enteric pathogen Salmonella enterica serovar Typhimurium. Therefore, we aim to characterize the impact of pyruvate sensing and uptake on fitness and growth of S. Typhimurium and the individual species of a defined microbiota consortium in vitro and in vivo.