Association between Brachyspira and irritable bowel syndrome with diarrhoea.

Association between Brachyspira and irritable bowel syndrome with diarrhoea.
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短螺旋体与肠易激综合征腹泻的相关性

DOI:
10.1136/gutjnl-2020-321466
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发表时间:
2021-06
期刊:
Gut
影响因子:
24.5
通讯作者:
Hansson GC
Hansson GC
中科院分区:
医学1区
文献类型:
--
作者:
Jabbar KS;Dolan B;Eklund L;Wising C;Ermund A;Johansson Å;Törnblom H;Simren M;Hansson GC

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肠道感染后IBS的发病率增加,表明微生物失衡的致病作用。然而,对粪便微生物群的分析并没有显示出一致的变化。在这里,我们使用元蛋白质组学来研究粘液驻留微生物群与IBS症状之间的潜在关联。从IBS患者和健康志愿者的乙状结肠活检中前瞻性地收集粘液样品,并通过质谱法分析其微生物蛋白质组成。通过免疫荧光、电子显微镜和实时PCR验证观察结果,并在第二个队列中进一步证实,并与临床特征和粘膜免疫应答的综合分析相关。结肠粘液样品的元蛋白质组学分析鉴定了IBS患者亚组中来自潜在致病性短螺旋体属物种的肽。使用多种诊断方法,在来自两个前瞻性队列的总共19/62(31%)患有IBS的患者中检测到粘膜短螺旋体定殖,而健康志愿者为0/31(p<0.001)。在两个队列中,IBS伴腹泻(IBS-D)的短螺旋体定殖患病率均为40%(p=0.02和p=0.006 vs对照组)。在20%的IBS患者中观察到短螺旋体附着于结肠细胞顶膜,并与加速的口腔-肛门运输、轻度粘膜炎症、肥大细胞活化以及与细菌摄取和离子流体稳态相关的分子途径的改变相关。甲硝唑治疗矛盾地促进短螺旋体搬迁到杯状细胞分泌颗粒-可能代表一种新的细菌策略,以逃避抗生素。黏菌短螺旋体定殖在IBS中显著更常见,并且与独特的临床、组织学和分子特征相关。我们的观察表明短螺旋体在IBS,特别是IBS-D的发病机制中的作用。
The incidence of IBS increases following enteric infections, suggesting a causative role for microbial imbalance. However, analyses of faecal microbiota have not demonstrated consistent alterations. Here, we used metaproteomics to investigate potential associations between mucus-resident microbiota and IBS symptoms. Mucus samples were prospectively collected from sigmoid colon biopsies from patients with IBS and healthy volunteers, and their microbial protein composition analysed by mass spectrometry. Observations were verified by immunofluorescence, electron microscopy and real-time PCR, further confirmed in a second cohort, and correlated with comprehensive profiling of clinical characteristics and mucosal immune responses. Metaproteomic analysis of colon mucus samples identified peptides from potentially pathogenic Brachyspira species in a subset of patients with IBS. Using multiple diagnostic methods, mucosal Brachyspira colonisation was detected in a total of 19/62 (31%) patients with IBS from two prospective cohorts, versus 0/31 healthy volunteers (p<0.001). The prevalence of Brachyspira colonisation in IBS with diarrhoea (IBS-D) was 40% in both cohorts (p=0.02 and p=0.006 vs controls). Brachyspira attachment to the colonocyte apical membrane was observed in 20% of patients with IBS and associated with accelerated oro-anal transit, mild mucosal inflammation, mast cell activation and alterations of molecular pathways linked to bacterial uptake and ion–fluid homeostasis. Metronidazole treatment paradoxically promoted Brachyspira relocation into goblet cell secretory granules—possibly representing a novel bacterial strategy to evade antibiotics. Mucosal Brachyspira colonisation was significantly more common in IBS and associated with distinctive clinical, histological and molecular characteristics. Our observations suggest a role for Brachyspira in the pathogenesis of IBS, particularly IBS-D.
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发表时间: 1982-01-01
影响因子: 9.4
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发表时间: 2010-01-07
期刊: German medical science : GMS e-journal
影响因子: --
作者:
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