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我比看起来更好:基于基因组的益生菌植物乳杆菌 IS-10506 的安全性评估。

I am better than I look: genome based safety assessment of the probiotic Lactiplantibacillus plantarum IS-10506.

机构信息

Centre for Healthy Eating & Food Innovation (HEFI), Maastricht University - campus Venlo, Villafloraweg 1, Venlo, 5928 SZ, the Netherlands.

Chair Group Youth Food and Health, Faculty of Science and Engineering, Maastricht University - campus Venlo, Villafloraweg 1, Venlo, 5928 SZ, the Netherlands.

出版信息

BMC Genomics. 2023 Sep 4;24(1):518. doi: 10.1186/s12864-023-09495-y.

Abstract

BACKGROUND

Safety of probiotic strains that are used in human and animal trials is a prerequisite. Genome based safety assessment of probiotics has gained popularity due its cost efficiency and speed, and even became a part of national regulation on foods containing probiotics in Indonesia. However, reliability of the safety assessment based only on a full genome sequence is not clear. Here, for the first time, we sequenced, assembled, and analysed the genome of the probiotic strain Lactiplantibacillus plantarum IS-10506, that was isolated from dadih, a traditional fermented buffalo milk. The strain has already been used as a probiotic for more than a decade, and in several clinical trials proven to be completely safe.

METHODS

The genome of the probiotic strain L. plantarum IS-10506 was sequenced using Nanopore sequencing technology, assembled, annotated and screened for potential harmful (PH) and beneficial genomic features. The presence of the PH features was assessed from general annotation, as well as with the use of specialised tools. In addition, PH regions in the genome were compared to all other probiotic and non-probiotic L. plantarum strains available in the NCBI RefSeq database.

RESULTS

For the first time, a high-quality complete genome of L. plantarum IS-10506 was obtained, and an extensive search for PH and a beneficial signature was performed. We discovered a number of PH features within the genome of L. plantarum IS-10506 based on the general annotation, including various antibiotic resistant genes (AMR); however, with a few exceptions, bioinformatics tools specifically developed for AMR detection did not confirm their presence. We further demonstrated the presence of the detected PH genes across multiple L. plantarum strains, including probiotics, and overall high genetic similarities between strains.

CONCLUSION

The genome of L. plantarum IS-10506 is predicted to have several PH features. However, the strain has been utilized as a probiotic for over a decade in several clinical trials without any adverse effects, even in immunocompromised children with HIV infection and undernourished children. This implies the presence of PH feature signatures within the probiotic genome does not necessarily indicate their manifestation during administration. Importantly, specialized tools for the search of PH features were found more robust and should be preferred over manual searches in a general annotation.

摘要

背景

用于人体和动物试验的益生菌菌株的安全性是前提条件。基于基因组的益生菌安全性评估因其成本效益和速度而受到欢迎,甚至成为印度尼西亚含益生菌食品国家法规的一部分。然而,仅基于全基因组序列进行安全性评估的可靠性尚不清楚。在这里,我们首次对从传统发酵水牛乳中分离出的益生菌菌株植物乳杆菌 IS-10506 进行测序、组装和分析。该菌株已作为益生菌使用了十多年,并在多项临床试验中被证明是完全安全的。

方法

使用纳米孔测序技术对益生菌菌株 L. plantarum IS-10506 的基因组进行测序,组装、注释并筛选潜在的有害(PH)和有益基因组特征。通过一般注释以及使用专门的工具评估 PH 特征的存在。此外,将基因组中的 PH 区域与 NCBI RefSeq 数据库中所有其他益生菌和非益生菌 L. plantarum 菌株进行比较。

结果

我们首次获得了 L. plantarum IS-10506 的高质量完整基因组,并对 PH 和有益特征进行了广泛搜索。我们根据一般注释在 L. plantarum IS-10506 的基因组中发现了一些 PH 特征,包括各种抗生素抗性基因(AMR);然而,除了少数例外,专门用于 AMR 检测的生物信息学工具并未确认其存在。我们进一步证明了在包括益生菌在内的多个 L. plantarum 菌株中存在检测到的 PH 基因,并且菌株之间具有很高的遗传相似性。

结论

L. plantarum IS-10506 的基因组预计具有几个 PH 特征。然而,该菌株已在多项临床试验中作为益生菌使用了十多年,即使在感染 HIV 的免疫功能低下儿童和营养不良儿童中也没有任何不良影响。这意味着益生菌基因组中 PH 特征的存在并不一定表明它们在给药期间会表现出来。重要的是,用于搜索 PH 特征的专用工具被发现更强大,并且应该优先于一般注释中的手动搜索。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69f2/10478331/6dae017d4287/12864_2023_9495_Fig1_HTML.jpg

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