Koga Hironori, Tamiya Yoshitaka, Mitsuyama Keiichi, Ishibashi Masahiko, Matsumoto Satoshi, Imaoka Akemi, Hara Taeko, Nakano Masatoshi, Ooeda Kazutoshi, Umezaki Yoshinori, Sata Michio
Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume, 830-0011, Japan.
Orin Hospital, Onojo, Japan.
Hepatol Int. 2013 Jun;7(2):767-74. doi: 10.1007/s12072-012-9408-x. Epub 2012 Nov 21.
Accumulating evidence suggests that deterioration of the gut flora contributes to the pathogenesis of alcoholic liver cirrhosis (ALC). However, the ALC flora profile and its response to probiotic treatment have not been fully examined. This double-blind placebo-controlled study aimed to evaluate whether the probiotic beverage Yakult 400 (Y400), which contains Lactobacillus casei strain Shirota, improves liver function in ALC patients, and to analyze the precise gut flora profile by real-time quantitative PCR (qPCR).
A total of 37 hospitalized ALC patients were randomly allocated to Y400 (n = 18) and placebo (n = 19) groups. Y400 or placebo was served twice a day during the first half of the four-week study. Serum concentrations of rapid-turnover proteins (i.e., transthyretin and transferrin), hypersensitive C-reactive protein, and interleukin-6 were measured weekly. qPCR analysis of fecal bacteria was performed biweekly; stocked fecal samples from 46 healthy subjects were used as references.
Serum transthyretin levels significantly increased in the Y400 group in week 3; similar-although statistically insignificant-increases were seen for transferrin and albumin. Levels of hypersensitive C-reactive protein, but not interleukin-6, significantly decreased in week 4. Before treatment, populations of obligate anerobic bacteria were significantly smaller and those of Enterobacteriaceae were larger in patients than in healthy subjects examined in a previous study. Y400 corrected this imbalance.
This is the first report describing the unique gut flora of ALC patients. Y400 treatment normalized the gut flora and improved liver function. These promising findings warrant further investigation in larger, multicenter studies.
越来越多的证据表明,肠道菌群的恶化有助于酒精性肝硬化(ALC)的发病机制。然而,ALC菌群概况及其对益生菌治疗的反应尚未得到充分研究。这项双盲安慰剂对照研究旨在评估含有干酪乳杆菌代田株的益生菌饮料养乐多400(Y400)是否能改善ALC患者的肝功能,并通过实时定量PCR(qPCR)分析精确的肠道菌群概况。
总共37名住院的ALC患者被随机分配到Y400组(n = 18)和安慰剂组(n = 19)。在为期四周的研究的前半段,每天给Y400组或安慰剂组服用两次药物。每周测量血清中快速周转蛋白(即转甲状腺素蛋白和转铁蛋白)、超敏C反应蛋白和白细胞介素-6的浓度。每两周进行一次粪便细菌的qPCR分析;使用46名健康受试者储存的粪便样本作为对照。
Y400组在第3周时血清转甲状腺素蛋白水平显著升高;转铁蛋白和白蛋白也有类似升高,尽管在统计学上无显著差异。超敏C反应蛋白水平在第4周时显著下降,但白细胞介素-6水平未下降。治疗前,与之前研究中检测的健康受试者相比,患者体内专性厌氧菌数量明显较少,肠杆菌科细菌数量较多。Y400纠正了这种失衡。
这是第一份描述ALC患者独特肠道菌群的报告。Y400治疗使肠道菌群正常化并改善了肝功能。这些有前景的发现值得在更大规模的多中心研究中进一步调查。