Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and McGuire VAMC, Richmond, VA, USA.
Aliment Pharmacol Ther. 2014 May;39(10):1113-25. doi: 10.1111/apt.12695. Epub 2014 Mar 16.
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 randomised 1:1 into LGG or placebo BID after being prescribed a standard diet and multi-vitamin regimen and were followed up 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 analysed between groups using correlation networks.
Thirty MHE patients (14 LGG and 16 placebo) completed the study without any differences in serious adverse events. However, self-limited diarrhoea was more frequent in LGG patients. A standard diet was maintained and LGG batches were comparable throughout. Only in the LGG-randomised 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, Lactobacillus GG is safe and well-tolerated in cirrhosis and is associated with a reduction in endotoxemia and dysbiosis.
在最小型肝性脑病（MHE）的肝硬化患者中，根据研究新药（IND）政策批准的个别益生菌菌株的安全性尚不清楚。
本 I 期研究的主要目的是评估益生菌鼠李糖乳杆菌 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。
MHE 患者在接受标准饮食和多种维生素治疗方案后，按 1:1 随机分为 LGG 或安慰剂组，每日两次，随访 8 周。在基线和研究结束时采集血清、尿液和粪便样本。在第 4 和第 8 周评估安全性。使用相关网络分析比较组间内毒素和全身炎症、使用多标签焦磷酸测序的微生物组、血清/尿液代谢组。
30 名 MHE 患者（14 名 LGG 和 16 名安慰剂）完成了研究，两组均无严重不良事件。然而，LGG 组更常出现自限性腹泻。标准饮食得到维持，LGG 批次在整个研究过程中保持一致。仅在 LGG 随机分组中，内毒素血症和 TNF-α降低，微生物组发生变化（肠杆菌科减少，未确定分类梭菌科 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。认知无变化。
在这项 I 期研究中，鼠李糖乳杆菌 GG 在肝硬化中安全且耐受良好，与内毒素血症和菌群失调减少相关。
