Randomised clinical trial: Lactobacillus GG modulates gut microbiome, metabolome and endotoxemia in patients with cirrhosis.
Randomised clinical trial: Lactobacillus GG modulates gut microbiome, metabolome and endotoxemia in patients with cirrhosis.
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DOI：
10.1111/apt.12695
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发表时间：
2014-05
影响因子：
7.6
通讯作者：
Gillevet PM
中科院分区：
文献类型：
--
作者：
Bajaj JS;Heuman DM;Hylemon PB;Sanyal AJ;Puri P;Sterling RK;Luketic V;Stravitz RT;Siddiqui MS;Fuchs M;Thacker LR;Wade JB;Daita K;Sistrun S;White MB;Noble NA;Thorpe C;Kakiyama G;Pandak WM;Sikaroodi M;Gillevet PM
根据研究性新药 (IND) 政策批准的个别益生菌菌株治疗伴有轻微肝性脑病 (MHE) 的肝硬化的安全性尚不清楚。这项 I 期研究的主要目的是评估益生菌乳杆菌 GG (LGG) 与安慰剂相比的安全性和耐受性，次要目的是通过 MHE 患者的认知、微生物组、代谢组和内毒素分析来探索其作用机制。合并 MHE 的肝硬化患者在接受标准饮食和多种维生素治疗后，按 1:1 的比例随机分为 LGG 或安慰剂 BID 组，并随访 8 周。在基线和研究结束时收集血清、尿液和粪便样本。在第 4 周和第 8 周评估安全性。使用相关网络对组间的内毒素和全身炎症、使用多标记焦磷酸测序的微生物组、血清/尿液代谢组进行分析。 30 名 MHE 患者（14 名 LGG 和 16 名安慰剂）完成了研究，严重不良事件没有任何差异。然而，LGG 患者的自限性腹泻更为常见。维持标准饮食，LGG 批次自始至终具有可比性。仅在 LGG 随机分组中，内毒素血症和 TNF-α 减少，微生物组发生变化（肠杆菌科减少，Clostridiales Incertae Sedis XIV 和 Lachnospiraceae 相对丰度增加），与氨基酸、维生素和次级 BA 代谢相关的代谢物/微生物组相关性发生变化。未发现认知发生变化。在这项 I 期研究中，LGG 在肝硬化治疗中是安全且耐受性良好的，并且与内毒素血症和生态失调的减少有关。
Safety of individual probiotic strains approved under Investigational New Drug (IND) policies in cirrhosis with minimal hepatic encephalopathy (MHE) is not clear. The primary aim of this phase I study was to evaluate the safety, tolerability of probiotic Lactobacillus GG (LGG) compared to placebo while secondary ones were to explore its mechanism of action using cognitive, microbiome, metabolome and endotoxin analysis in MHE patients. Cirrhotic patients with MHE patients were randomized 1:1 into LGG or placebo BID after being prescribed a standard diet and multi-vitamin regimen and were followed for 8 weeks. Serum, urine and stool samples were collected at baseline and study-end. Safety was assessed at weeks 4 and 8. Endotoxin and systemic inflammation, microbiome using multi-tagged pyrosequencing, serum/urine metabolome were analyzed between groups using correlation networks. 30 MHE patients (14 LGG and 16 placebo) completed the study without any differences in serious adverse events. However, self-limited diarrhea was more frequent in LGG patients. A standard diet was maintained and LGG batches were comparable throughout. Only in the LGG-randomized group, endotoxemia and TNF-α decreased, microbiome changed (reduced Enterobacteriaceae and increased Clostridiales Incertae Sedis XIV and Lachnospiraceae relative abundance) with changes in metabolite/microbiome correlations pertaining to amino acid, vitamin and secondary BA metabolism. No change in cognition was found. In this phase I study, LGG is safe and well-tolerated in cirrhosis and is associated with a reduction in endotoxemia and dysbiosis.
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影响因子：
3.7
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
通讯作者：
Gillevet PM
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：
3
作者：
BERGNER, M;BOBBITT, RA;GILSON, BS
通讯作者：
GILSON, BS
影响因子：
3.2
作者：
Lebeer, Sarah;De Keersmaecker, Sigrid C. J.;Vanderleyden, Jos
通讯作者：
Vanderleyden, Jos
影响因子：
9.8
作者：
Bajaj, Jasmohan S.;Saeian, Kia;Binion, David G.
通讯作者：
Binion, David G.