Douillard François P, Mora Diego, Eijlander Robyn T, Wels Michiel, de Vos Willem M
Research Program Unit Immunobiology, Medicum, University of Helsinki, Helsinki, Finland.
Department of Food Hygiene and Environmental Health, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland.
PLoS One. 2018 Feb 16;13(2):e0192452. doi: 10.1371/journal.pone.0192452. eCollection 2018.
Several probiotic-marketed formulations available for the consumers contain live lactic acid bacteria and/or bifidobacteria. The multispecies product commercialized as VSL#3 has been used for treating various gastro-intestinal disorders. However, like many other products, the bacterial strains present in VSL#3 have only been characterized to a limited extent and their efficacy as well as their predicted mode of action remain unclear, preventing further applications or comparative studies. In this work, the genomes of all eight bacterial strains present in VSL#3 were sequenced and characterized, to advance insights into the possible mode of action of this product and also to serve as a basis for future work and trials. Phylogenetic and genomic data analysis allowed us to identify the 7 species present in the VSL#3 product as specified by the manufacturer. The 8 strains present belong to the species Streptococcus thermophilus, Lactobacillus acidophilus, Lactobacillus paracasei, Lactobacillus plantarum, Lactobacillus helveticus, Bifidobacterium breve and B. animalis subsp. lactis (two distinct strains). Comparative genomics revealed that the draft genomes of the S. thermophilus and L. helveticus strains were predicted to encode most of the defence systems such as restriction modification and CRISPR-Cas systems. Genes associated with a variety of potential probiotic functions were also identified. Thus, in the three Bifidobacterium spp., gene clusters were predicted to encode tight adherence pili, known to promote bacteria-host interaction and intestinal barrier integrity, and to impact host cell development. Various repertoires of putative signalling proteins were predicted to be encoded by the genomes of the Lactobacillus spp., i.e. surface layer proteins, LPXTG-containing proteins, or sortase-dependent pili that may interact with the intestinal mucosa and dendritic cells. Taken altogether, the individual genomic characterization of the strains present in the VSL#3 product confirmed the product specifications, determined its coding capacity as well as identified potential probiotic functions.
市面上有几种面向消费者销售的益生菌制剂，其中含有活的乳酸菌和/或双歧杆菌。作为VSL#3商业化的多菌种产品已被用于治疗各种胃肠道疾病。然而，与许多其他产品一样，VSL#3中存在的细菌菌株仅在有限程度上得到了表征，其功效以及预测的作用模式仍不清楚，这阻碍了进一步的应用或比较研究。在这项工作中，对VSL#3中存在的所有八种细菌菌株的基因组进行了测序和表征，以深入了解该产品可能的作用模式，并为未来的工作和试验提供基础。系统发育和基因组数据分析使我们能够确定VSL#3产品中制造商指定的7种菌种。目前存在的8个菌株分别属于嗜热链球菌、嗜酸乳杆菌、副干酪乳杆菌、植物乳杆菌、瑞士乳杆菌、短双歧杆菌和动物双歧杆菌亚种乳酸亚种（两个不同的菌株）。比较基因组学表明，嗜热链球菌和瑞士乳杆菌菌株的草图基因组预计编码大多数防御系统，如限制修饰和CRISPR-Cas系统。还鉴定了与多种潜在益生菌功能相关的基因。因此，在三种双歧杆菌属中，基因簇预计编码紧密粘附菌毛，已知其可促进细菌与宿主的相互作用和肠道屏障完整性，并影响宿主细胞发育。预计乳杆菌属的基因组会编码各种假定的信号蛋白，即表层蛋白、含LPXTG的蛋白或可能与肠粘膜和树突状细胞相互作用的分选酶依赖性菌毛。总的来说，VSL#3产品中菌株的个体基因组表征证实了产品规格，确定了其编码能力，并鉴定了潜在的益生菌功能。
