Modulation of the metabiome by rifaximin in patients with cirrhosis and minimal hepatic encephalopathy.
Modulation of the metabiome by rifaximin in patients with cirrhosis and minimal hepatic encephalopathy.
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DOI：
10.1371/journal.pone.0060042
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Gillevet PM
中科院分区：
文献类型：
--
作者：
Bajaj JS;Heuman DM;Sanyal AJ;Hylemon PB;Sterling RK;Stravitz RT;Fuchs M;Ridlon JM;Daita K;Monteith P;Noble NA;White MB;Fisher A;Sikaroodi M;Rangwala H;Gillevet PM
肝性脑病（HE）代表肝硬化中肠-肝-脑轴功能障碍，可对结局产生负面影响。这种改变的肠-脑关系已经使用肠道选择性抗生素（如利福昔明）治疗，可改善HE的认知功能，特别是其亚临床形式，轻微HE（MHE）。然而，利福昔明在MHE中作用的确切机制尚不清楚。我们假设利福昔明对肠道菌群及其终产物的调节会影响肠-脑轴并改善肝硬化患者的认知能力。目的对MHE中利福昔明后的微生物组、代谢组和认知变化进行系统生物学分析。在基线和利福昔明550 mg BID后8周，20名MHE患者接受认知测试、内毒素分析、尿/血清代谢组学（GC和LC-MS）和粪便微生物组评估（多标记焦磷酸测序）。使用推荐的系统生物学技术分析认知、内毒素、血清/尿液代谢物（和微生物组）的变化。具体地，在利福昔明之前和之后分析微生物群和代谢组之间的相关网络。利福昔明治疗后，认知（7项测试中有6项改善，p<0.01）和内毒素血症（0.55至0.48 Eu/ml，p =0.02）有显著改善。 利福昔明给药后，血清饱和脂肪酸（肉豆蔻酸、辛酸、棕榈酸、棕榈油酸、油酸和二十烷酸）和不饱和脂肪酸（亚油酸、亚麻酸、γ-亚麻酸和花生四烯酸）显著增加。除了韦荣球菌科的适度减少和真杆菌科的增加外，未观察到显著的微生物变化。利福昔明导致相关网络上的网络连接和聚类显著减少。以肠杆菌科、卟啉单胞菌科和拟杆菌科为中心的网络表明从致病代谢物向有益代谢物的联系和更好的认知转变，而以土著类群为中心的网络保持相似。利福昔明与MHE中认知功能和内毒素血症的改善相关，这伴随着肠道细菌与代谢物的联系的改变，而微生物丰度没有显著变化。ClinicalTrials.gov www.example.com
Hepatic encephalopathy (HE) represents a dysfunctional gut-liver-brain axis in cirrhosis which can negatively impact outcomes. This altered gut-brain relationship has been treated using gut-selective antibiotics such as rifaximin, that improve cognitive function in HE, especially its subclinical form, minimal HE (MHE). However, the precise mechanism of the action of rifaximin in MHE is unclear. We hypothesized that modulation of gut microbiota and their end-products by rifaximin would affect the gut-brain axis and improve cognitive performance in cirrhosis. Aim To perform a systems biology analysis of the microbiome, metabolome and cognitive change after rifaximin in MHE. Twenty cirrhotics with MHE underwent cognitive testing, endotoxin analysis, urine/serum metabolomics (GC and LC-MS) and fecal microbiome assessment (multi-tagged pyrosequencing) at baseline and 8 weeks post-rifaximin 550 mg BID. Changes in cognition, endotoxin, serum/urine metabolites (and microbiome were analyzed using recommended systems biology techniques. Specifically, correlation networks between microbiota and metabolome were analyzed before and after rifaximin. There was a significant improvement in cognition(six of seven tests improved,p<0.01) and endotoxemia (0.55 to 0.48 Eu/ml, p = 0.02) after rifaximin. There was a significant increase in serum saturated (myristic, caprylic, palmitic, palmitoleic, oleic and eicosanoic) and unsaturated (linoleic, linolenic, gamma-linolenic and arachnidonic) fatty acids post-rifaximin. No significant microbial change apart from a modest decrease in Veillonellaceae and increase in Eubacteriaceae was observed. Rifaximin resulted in a significant reduction in network connectivity and clustering on the correlation networks. The networks centered on Enterobacteriaceae, Porphyromonadaceae and Bacteroidaceae indicated a shift from pathogenic to beneficial metabolite linkages and better cognition while those centered on autochthonous taxa remained similar. Rifaximin is associated with improved cognitive function and endotoxemia in MHE, which is accompanied by alteration of gut bacterial linkages with metabolites without significant change in microbial abundance. ClinicalTrials.gov NCT01069133
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影响因子：
2.9
作者：
Gillevet, Patrick;Sikaroodi, Masoumeh;Keshavarzian, Ali;Mutlu, Ece A.
通讯作者：
Mutlu, Ece A.
影响因子：
64.8
作者：
Arumugam, Manimozhiyan;Raes, Jeroen;Pelletier, Eric;Le Paslier, Denis;Yamada, Takuji;Mende, Daniel R.;Fernandes, Gabriel R.;Tap, Julien;Bruls, Thomas;Batto, Jean-Michel;Bertalan, Marcelo;Borruel, Natalia;Casellas, Francesc;Fernandez, Leyden;Gautier, Laurent;Hansen, Torben;Hattori, Masahira;Hayashi, Tetsuya;Kleerebezem, Michiel;Kurokawa, Ken;Leclerc, Marion;Levenez, Florence;Manichanh, Chaysavanh;Nielsen, H. Bjorn;Nielsen, Trine;Pons, Nicolas;Poulain, Julie;Qin, Junjie;Sicheritz-Ponten, Thomas;Tims, Sebastian;Torrents, David;Ugarte, Edgardo;Zoetendal, Erwin G.;Wang, Jun;Guarner, Francisco;Pedersen, Oluf;de Vos, Willem M.;Brunak, Soren;Dore, Joel;Weissenbach, Jean;Ehrlich, S. Dusko;Bork, Peer
通讯作者：
Bork, Peer
影响因子：
6.7
作者：
Kesarwani, Meenu;Hazan, Ronen;Rahme, Laurence G.
通讯作者：
Rahme, Laurence G.
影响因子：
13.5
作者：
Puri, Puneet;Wiest, Michelle M.;Cheung, Onpan;Mirshahi, Faridoddin;Sargeant, Carol;Min, Hae-Ki;Contos, Melissa J.;Sterling, Richard K.;Fuchs, Michael;Zhou, Huiping;Watkins, Steven M.;Sanyal, Arun J.
通讯作者：
Sanyal, Arun J.
影响因子：
9.8
作者：
Bajaj, Jasmohan S.;Saeian, Kia;Binion, David G.
通讯作者：
Binion, David G.