Role of dietary sulfonates in the stimulation of intestinal bacteria promoting gut inflammation

点击翻译按钮获取中文摘要

The intestinal microbiome is crucial for the maturation and proper functioning of the immune system. Disturbances in the interaction between the intestinal microbiota and the mucosal immune system may lead to inflammatory bowel diseases. In which way a disturbed microbiota may contribute to an inflamed gut is not completely understood, but it has been demonstrated that the proliferation of pro-inflammatory intestinal bacteria may lead to gut inflammation in a susceptible host. Diet is the main source of bacterial substrates in the digestive tract and therefore influences the composition and activity of the intestinal microbiota. A diet rich in saturated fats has been demonstrated in mice to stimulate the growth of pro-inflammatory Bilophila wadsworthia by shifting the bile-acid spectrum toward a higher proportion of taurine conjugates. The sulfonyl group of taurine provides sulfite, which is used by this organism as an electron acceptor and becomes reduced to sulfide. Host enzymes oxidize sulfide to thiosulfate, which in turn stimulates the growth of pathogenic Salmonella. With the present project we aim to investigate whether dietary sulfonated compounds such as sulfoquinovosyldiacylglycerol (SQDG), which occurs in the membranes of chloroplasts and is ingested with green fruits and leafy vegetables, may contribute to the pool of sulfonates, lead to intestinal sulfide production and stimulate the growth of colitogenic bacteria such as B. wadsworthia. In view of the potential stimulation of enteropathogenic bacteria by thiosulfate, we aim to clarify, to which extent dietary sulfonates, in particular SQDG and sulfoquinovose (SQ), undergo further microbial degradation. Escherichia coli has recently been demonstrated to harbor a set of enzymes that catalyze the breakdown of SQ to 2,3-dihydroxy-1-sulfonate, which may contribute to the sulfonate pool in the intestinal tract. We will examine whether intestinal bacteria other than B. wadsworthia contribute to the formation of sulfide from sulfonates. Such bacteria will be isolated and the biochemical pathways involved in sulfonate utilization will be identified. We will test whether sulfonate utilizers have pro-inflammatory properties like B. wadsworthia. Using mouse models we will investigate how these dietary sulfonates affect the intestinal microbiome and examine whether these effects promote gut inflammation.