Gut microbiota, metabolome and immune signatures in patients with uncomplicated diverticular disease

Gut microbiota, metabolome and immune signatures in patients with uncomplicated diverticular disease
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DOI:
10.1136/gutjnl-2016-312377
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发表时间:
2017-07-01
期刊:
GUT
影响因子:
24.5
通讯作者:
Festi, Davide
Festi, Davide
中科院分区:
医学1区
文献类型:
--
作者:
Barbara, Giovanni;Scaioli, Eleonora;Festi, Davide

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目的肠道微生物群参与憩室病症状和并发症的发展已被频繁假设。我们的目的是探讨结肠免疫细胞,肠道菌群和代谢组在憩室病患者的描述性,横断面,pilot study.Design结肠镜活检和问卷表型,患者被归类为憩室病或症状性单纯性憩室病,无症状的受试者作为对照。粘液免疫细胞,在憩室区和未受影响的网站,定量免疫组织化学。通过系统发育平台高分类指纹(HTF)-Microbi分析粘膜和粪便微生物群。结果与对照组相比,憩室患者,无论症状如何,结肠巨噬细胞增加>70%。他们的粪便微生物群显示梭菌簇IV耗尽。有症状患者与无症状患者相比,梭菌IX群、梭杆菌和乳酸杆菌减少。巨噬细胞与粘膜梭菌IV群和阿克曼氏菌呈负相关。憩室病的尿和粪便代谢组变化涉及马尿酸和犬尿氨酸途径。六种尿分子允许区分憩室疾病和对照组,准确率>95%。结论结肠憩室疾病患者表现出与粘膜巨噬细胞浸润相关的抗炎活性的微生物群成员耗竭。代谢组学特征与炎症通路和肠道神经运动功能障碍有关,并显示出区分憩室亚组和对照组的能力。这些数据为进一步的大规模研究铺平了道路,这些研究旨在识别对憩室病患者具有潜在诊断价值的微生物群特征。
Objective The engagement of the gut microbiota in the development of symptoms and complications of diverticular disease has been frequently hypothesised. Our aim was to explore colonic immunocytes, gut microbiota and the metabolome in patients with diverticular disease in a descriptive, cross-sectional, pilot study.Design Following colonoscopy with biopsy and questionnaire phenotyping, patients were classified into diverticulosis or symptomatic uncomplicated diverticular disease; asymptomatic subjects served as controls. Mucosal immunocytes, in the diverticular region and in unaffected sites, were quantified with immunohistochemistry. Mucosa and faecal microbiota were analysed by the phylogenetic platform high taxonomic fingerprint (HTF)-Microbi. Array, while the metabolome was assessed by 1H nuclear magnetic resonance.Results Compared with controls, patients with diverticula, regardless of symptoms, had a >70% increase in colonic macrophages. Their faecal microbiota showed depletion of Clostridium cluster IV. Clostridium cluster IX, Fusobacterium and Lactobacillaceae were reduced in symptomatic versus asymptomatic patients. A negative correlation was found between macrophages and mucosal Clostridium cluster IV and Akkermansia. Urinary and faecal metabolome changes in diverticular disease involved the hippurate and kynurenine pathways. Six urinary molecules allowed to discriminate diverticular disease and control groups with >95% accuracy.Conclusions Patients with colonic diverticular disease show depletion of microbiota members with anti-inflammatory activity associated with mucosal macrophage infiltration. Metabolome profiles were linked to inflammatory pathways and gut neuromotor dysfunction and showed the ability to discriminate diverticular subgroups and controls. These data pave the way for further large-scale studies specifically aimed at identifying microbiota signatures with a potential diagnostic value in patients with diverticular disease.