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

肠道微生物组对于免疫系统的成熟和正常运作至关重要。肠道微生物群和粘膜免疫系统之间相互作用的紊乱可能导致炎症性肠病。受干扰的微生物群可能以何种方式导致发炎的肠道尚未完全了解，但已证明促炎性肠道细菌的增殖可能导致易感宿主的肠道炎症。饮食是消化道中细菌底物的主要来源，因此影响肠道微生物群的组成和活性。富含饱和脂肪的饮食已在小鼠中被证明通过将胆汁酸谱向更高比例的牛磺酸缀合物转移来刺激促炎性嗜胆汁虫的生长。牛磺酸的磺酰基提供亚硫酸盐，亚硫酸盐被该生物体用作电子受体并被还原为硫化物。宿主酶将硫化物氧化成硫代硫酸盐，硫代硫酸盐反过来刺激致病性沙门氏菌的生长。本项目旨在研究膳食中的磺化化合物，如磺基喹诺糖基二酰甘油（SQDG），它发生在叶绿体的膜中，与绿色水果和叶菜一起摄入，是否可能有助于磺酸盐的库，导致肠道硫化物的产生，并刺激大肠杆菌如B的生长。wadsobiria。鉴于硫代硫酸盐对肠道致病菌的潜在刺激，我们的目的是澄清，在何种程度上膳食磺酸盐，特别是SQDG和磺基喹诺糖（SQ），进行进一步的微生物降解。大肠杆菌最近被证明含有一组酶，催化SQ分解为2，3-二羟基-1-磺酸盐，这可能有助于肠道中的磺酸盐库。我们将检查除B以外的肠道细菌。水硫酸盐有助于从磺酸盐形成硫化物。这些细菌将被分离，并将确定磺酸盐利用所涉及的生化途径。我们将测试磺酸盐利用剂是否具有像B那样的促炎特性。wadsobiria。使用小鼠模型，我们将研究这些膳食磺酸盐如何影响肠道微生物组，并检查这些影响是否会促进肠道炎症。

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.