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

膳食磺酸盐在刺激肠道细菌促进肠道炎症中的作用

• 批准号: 316145477
• 负责人: Dr. Annett Braune, since 4/2019
• 金额: --
• 依托单位: Abteilung Gastrointestinale Mikrobiologie (GAMI) (aufgelöst)
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 2016
• 资助国家: 德国
• 起止时间: 2015-12-31 至 2020-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/316145477?language=en
• 关键词: Role; dietary; sulfonates; stimulation; intestinal

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.

肠道微生物群对免疫系统的成熟和正常运作至关重要。肠道微生物区系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。微生物区系紊乱是如何导致肠道发炎的，目前还不完全清楚，但已经证明，促炎肠道细菌的增殖可能会导致易感宿主的肠道炎症。饮食是消化道细菌底物的主要来源，因此影响肠道微生物区系的组成和活性。一种富含饱和脂肪的饮食已经在小鼠身上被证明可以通过将胆汁酸谱向更高比例的牛磺酸结合物转移来刺激促炎的华氏双歧杆菌的生长。牛磺酸的磺酰基提供亚硫酸盐，亚硫酸盐被这种生物用作电子受体，并还原为硫化物。宿主酶将硫化物氧化成硫代硫酸盐，进而刺激致病沙门氏菌的生长。在本项目中，我们的目标是调查饮食中的磺化化合物，如磺化喹诺酮二甘油(SQDG)，它存在于叶绿体的膜上，与绿色水果和叶蔬菜一起摄入，是否有助于磺酸盐池，导致肠道硫化物的产生，并刺激产肠结肠菌，如B.wadsworth的生长。鉴于硫代硫酸盐对肠道致病细菌的潜在刺激作用，我们的目的是阐明日粮中的磺酸盐，特别是SQDG和磺基喹诺糖(SQ)，在何种程度上会进一步被微生物降解。大肠杆菌最近被证明含有一组酶，可以催化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池。我们将研究肠道细菌而不是沃兹沃氏杆菌是否有助于从磺酸盐中形成硫化物。这样的细菌将被分离出来，并将确定涉及磺酸盐利用的生化途径。我们将测试磺酸盐利用剂是否具有像B.wadsworth一样的促炎特性。利用小鼠模型，我们将研究这些饮食磺酸盐如何影响肠道微生物群，并检查这些影响是否促进肠道炎症。