Department of Agricultural and Food Sciences, University of Bologna, Viale Fanin 42, Bologna, Italy.
BIOLAB RESEARCH srl, via E. Mattei 3, 28100, Novara, Italy.
BMC Med. 2020 Jun 17;18(1):153. doi: 10.1186/s12916-020-01607-9.
A connection between amyotrophic lateral sclerosis (ALS) and altered gut microbiota composition has previously been reported in animal models. This work is the first prospective longitudinal study addressing the microbiota composition in ALS patients and the impact of a probiotic supplementation on the gut microbiota and disease progression.
Fifty patients and 50 matched controls were enrolled. The microbial profile of stool samples from patients and controls was analyzed via PCR-Denaturing Gradient Gel Electrophoresis, and the main microbial groups quantified via qPCR. The whole microbiota was then analyzed via next generation sequencing after amplification of the V3-V4 region of 16S rDNA. Patients were then randomized to receive probiotic treatment or placebo and followed up for 6 months with ALSFRS-R, BMI, and FVC%.
The results demonstrate that the gut microbiota of ALS patients is characterized by some differences with respect to controls, regardless of the disability degree. Moreover, the gut microbiota composition changes during the course of the disease as demonstrated by the significant decrease in the number of observed operational taxonomic unit during the follow-up. Interestingly, an unbalance between potentially protective microbial groups, such as Bacteroidetes, and other with potential neurotoxic or pro-inflammatory activity, such as Cyanobacteria, has been shown. The 6-month probiotic treatment influenced the gut microbial composition; however, it did not bring the biodiversity of intestinal microbiota of patients closer to that of control subjects and no influence on the progression of the disease measured by ALSFRS-R was demonstrated.
Our study poses the bases for larger clinical studies to characterize the microbiota changes as a novel ALS biomarker and to test new microbial strategy to ameliorate the health status of the gut.
CE 107/14, approved by the Ethics Committee of the "Maggiore della Carità" University Hospital, Italy.
先前的动物模型研究报告称，肌萎缩侧索硬化症（ALS）与肠道微生物群落组成的改变之间存在关联。这项工作是第一项针对 ALS 患者肠道微生物群落组成以及益生菌补充对肠道微生物群落和疾病进展影响的前瞻性纵向研究。
纳入了 50 名患者和 50 名匹配的对照者。通过聚合酶链反应-变性梯度凝胶电泳分析患者和对照者粪便样本的微生物谱，并通过 qPCR 定量主要微生物群。然后，通过扩增 16S rDNA 的 V3-V4 区，对全微生物群进行下一代测序分析。患者随后随机接受益生菌治疗或安慰剂治疗，并通过 ALSFRS-R、BMI 和 FVC%随访 6 个月。
结果表明，无论残疾程度如何，ALS 患者的肠道微生物群都具有一些与对照组不同的特征。此外，正如在随访过程中观察到的操作分类单元数量显著减少所表明的那样，疾病过程中肠道微生物群落组成发生了变化。有趣的是，已经显示出潜在保护性微生物群（如拟杆菌门）与其他具有潜在神经毒性或促炎活性的微生物群（如蓝细菌门）之间的失衡。6 个月的益生菌治疗影响了肠道微生物群落组成；然而，它并没有使患者肠道微生物群落的多样性更接近对照组，也没有证明对 ALSFRS-R 测量的疾病进展有影响。
我们的研究为更大规模的临床研究奠定了基础，以表征微生物群变化作为 ALS 的新型生物标志物，并测试改善肠道健康状况的新微生物策略。
CE 107/14，获得意大利“Maggiore della Carità”大学医院伦理委员会的批准。
