Gut microbiota dysbiosis is associated with inflammation and bacterial translocation in mice with CCl4-induced fibrosis.
Gut microbiota dysbiosis is associated with inflammation and bacterial translocation in mice with CCl4-induced fibrosis.
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DOI：
10.1371/journal.pone.0023037
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Francés R
中科院分区：
文献类型：
--
作者：
Gómez-Hurtado I;Santacruz A;Peiró G;Zapater P;Gutiérrez A;Pérez-Mateo M;Sanz Y;Francés R
肠道是引起晚期肝硬变感染的内源性细菌的主要来源。肠屏障功能障碍在肝硬变中已被描述，并解释了细菌移位率增加的原因。我们推测，随着实验性肝硬变的诱导，微生物区系的组成可能会受到影响并发生变化，从而影响炎症反应。采用四氯化碳体重控制灌胃的方法诱导Balb/c小鼠进行性肝损伤。分别于第6、10、13和16周对一组小鼠(n = 6次/周)和对照组(n = 4次/周)进行剖腹手术。在剖腹手术时采集肝组织标本、肠系膜淋巴结、肠内容物和血液。检测肝纤维化分级、促纤维化基因表达、肠道细菌组成、细菌移位、宿主特异性丁酸受体GPR-43和血清细胞因子水平。促纤维化标志物的表达显著高于对照组，并与四氯化碳的累积剂量相关。对照小鼠的细菌易位事件比处理组的小鼠少。与对照动物和其他肠道常见细菌物种相比，治疗组小鼠的革兰氏阳性厌氧梭菌数量减少，改变了需氧/厌氧比例。这一事实与治疗组小鼠中性粒细胞中GPR43基因表达下降有关，与治疗组小鼠血清中肿瘤坏死因子-α和白介素6水平的上调呈负相关。这种促炎情景有利于接受治疗的动物的血液细菌移位，在相同的几周内显示出最高的细菌移位率和需氧/厌氧比率。在四氯化碳处理的小鼠中，肠道微生物区系的改变与炎症环境的发展、纤维化进展和细菌移位有关。
Gut is the major source of endogenous bacteria causing infections in advanced cirrhosis. Intestinal barrier dysfunction has been described in cirrhosis and account for an increased bacterial translocation rate. We hypothesize that microbiota composition may be affected and change along with the induction of experimental cirrhosis, affecting the inflammatory response. Progressive liver damage was induced in Balb/c mice by weight-controlled oral administration of carbon tetrachloride. Laparotomies were performed at weeks 6, 10, 13 and 16 in a subgroup of treated mice (n = 6/week) and control animals (n = 4/week). Liver tissue specimens, mesenteric lymph nodes, intestinal content and blood were collected at laparotomies. Fibrosis grade, pro-fibrogenic genes expression, gut bacterial composition, bacterial translocation, host's specific butyrate-receptor GPR-43 and serum cytokine levels were measured. Expression of pro-fibrogenic markers was significantly increased compared with control animals and correlated with the accumulated dose of carbon tetrachloride. Bacterial translocation episodes were less frequent in control mice than in treated animals. Gram-positive anaerobic Clostridia spp count was decreased in treated mice compared with control animals and with other gut common bacterial species, altering the aerobic/anaerobic ratio. This fact was associated with a decreased gene expression of GPR43 in neutrophils of treated mice and inversely correlated with TNF-alpha and IL-6 up-regulation in serum of treated mice along the study protocol. This pro-inflammatory scenario favoured blood bacterial translocation in treated animals, showing the highest bacterial translocation rate and aerobic/anaerobic ratio at the same weeks. Gut microbiota alterations are associated with the development of an inflammatory environment, fibrosis progression and bacterial translocation in carbon tetrachloride-treated mice.
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影响因子：
2.8
作者：
Lührs, H;Gerke, T;Menzel, T
通讯作者：
Menzel, T
影响因子：
9.8
作者：
Malinen, E;Rinttilä, T;Palva, A
通讯作者：
Palva, A
影响因子：
4.4
作者：
Matsuki, T;Watanabe, K;Tanaka, R
通讯作者：
Tanaka, R
DOI：
10.4049/jimmunol.182.1.538
发表时间：
2009-01-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Kumar A;Wu H;Collier-Hyams LS;Kwon YM;Hanson JM;Neish AS
通讯作者：
Neish AS
影响因子：
29.4
作者：
Caplan, MS;Miller-Catchpole, R;Thomson, R
通讯作者：
Thomson, R