炎症性肠病(IBD),包括克罗恩病(CD)和溃疡性结肠炎(UC),与宿主-微生物相互作用的丧失或不平衡有关。然而,这种蛋白质水平的相互作用在很大程度上仍然未知。这里,我们应用耗竭辅助的元蛋白质组学方法来获得深入的IBD宿主-微生物组关联网络,其中核心宿主蛋白从那些维持粘膜稳态的对照转移到那些参与炎症的,蛋白水解,和肠屏障在IBD。微生物节点如短链脂肪酸生产者相关的宿主-微生物串扰在IBD中被炎性蛋白丢失或抑制。在蛋白质-蛋白质关联网络的指导下,我们采用蛋白质组学和脂质组学研究UC相关核心蛋白S100A8,S100A9和细胞因子(IL-1β,IL-6和TNF-α)对肠道细菌的作用。这些蛋白质抑制了粪便来源的体外群落中嘌呤核苷酸的生物合成,在IBD粪便样本中全部减少。单物种研究表明,S100A8,S100A9和细胞因子可以协同或拮抗地改变肠道细菌细胞内和分泌的蛋白质组,与S100A8和S100A9组合可有效抑制有益的青春期双歧杆菌。此外,这些炎性蛋白仅改变了草根Ruminococcus的胞外蛋白而不是胞内蛋白。一般来说,S100A8比S100A9、IL-1β、IL-6和TNF-α。但是在两种蛋白质的存在下,肠道细菌比S100A9降解更多的S100A8。在被调查的物种中,仅在接受S100A8,S100A9和细胞因子联合治疗的普通拟杆菌中观察到明显的脂质改变.这些结果提供了以炎症蛋白为中心的宿主-微生物分子相互作用的宝贵资源。
Inflammatory bowel disease (IBD), including Crohn\'s disease (CD) and ulcerative colitis (UC), is associated with a loss or an imbalance of host-microorganism interactions. However, such interactions at protein levels remain largely unknown. Here, we applied a depletion-assisted metaproteomics approach to obtain in-depth host-microbiome association networks of IBD, where the core host proteins shifted from those maintaining mucosal homeostasis in controls to those involved in inflammation, proteolysis, and intestinal barrier in IBD. Microbial nodes such as short-chain fatty acid producer-related host-microbial crosstalk were lost or suppressed by inflammatory proteins in IBD. Guided by protein-protein association networks, we employed proteomics and lipidomics to investigate the effects of UC-related core proteins
S100A8, S100A9, and cytokines (IL-1β, IL-6, and TNF-α) on gut bacteria. These proteins suppressed purine nucleotide biosynthesis in stool-derived in vitro communities, which was all reduced in IBD stool samples. Single species study revealed that
S100A8, S100A9, and cytokines can synergistically or antagonistically alter gut bacteria intracellular and secreted proteome, with combined
S100A8 and S100A9 potently inhibiting beneficial Bifidobacterium adolescentis. Furthermore, these inflammatory proteins only altered the extracellular but not intracellular proteins of Ruminococcus gnavus. Generally,
S100A8 induced more significant bacterial proteome changes than S100A9, IL-1β, IL-6, and TNF-α. But gut bacteria degrade significantly more
S100A8 than S100A9 in the presence of both proteins. Among the investigated species, distinct lipid alterations were only observed in Bacteroides vulgatus treated with combined S100A8, S100A9, and cytokines. These results provided a valuable resource of inflammatory protein centric host-microbial molecular interactions.