Microbial sulfonolipid biosynthesis and degradation in the human gut

ongoing

Sulfobacins are sulfonated lipids that are bacterially synthesized in the gut and modulate the immune system and dampen intestinal inflammation. Therefore, they are considered as potential therapeutics for targeted microbiome-oriented interventions in the increasing number of cases of inflammatory bowel disease. However, the effects of sulfobacins on the gut microbiota, the degradation processes, and the key enzymes of the microbial biosynthetic pathway are unknown. The complex human gut microbiota directly affects host health by influencing the abundance of metabolites, aiding in nutrient digestion, protecting against enteropathogens, and enhancing immune system activity. Dysbiosis is usually associated with disease and intestinal inflammation. It is a crucial prerequisite for microbiome-oriented interventions to elucidate the ecophysiology of the species that drive these pathways. The existence of sulfobacin decomposition has not been shown yet in any habitat but sulfonated lipid degradation is usually correlated with increased availability of reduced sulfur compounds, which can also act as signaling molecules. Thus, project SLIDES aims to discover the species and that drive the degradation in the human gut and the biosynthesis pathway. This will be accomplished by a combination of molecular biology and functional microbiome analysis methods. This will result in: (1) the elucidation of the sulfobacin biosynthesis pathway and its genes by reverse genetics, (2) the discovery of sulfobacin degraders and the impact of sulfobacins on the gut microbiota by monitoring the temporal dynamics of responsive taxa, metabolic activity, and metabolite changes in sulfobacin-stimulated human fecal microcosms, and (3) the description of ecophysiology of sulfobacin degrading species, the required genes, and the degradation metabolites produced using stable isotope tracing.