Toh Kai Yee, Toh Tzi Shin, Chua Khi Pin, Rajakumar Priscilla, Lee Jonathan Wei Jie, Chong Chun Wie
AMILI Pte Ltd, 89 Science Park Drive #03-09, The Rutherford, Lobby C, Singapore Science Park 1, Singapore, 118261, Singapore.
Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
Gut Pathog. 2024 Oct 5;16(1):56. doi: 10.1186/s13099-024-00650-8.
Age-related gut microbial changes have been widely investigated over the past decade. Most of the previous age-related microbiome studies were conducted on the Western population, and the short-read sequencing (e.g., 16S V4 or V3-V4 region) was the most common microbiota profiling method. We evaluated the gut compositional differences using the long-read sequencing approach (i.e., PacBio sequencing targeting the full-length V1-V9 regions) to enable a deeper taxonomic resolution and better characterize the gut microbiome of Singaporeans from different age groups.
A total of 83 research participants were included in this study. Although no significant differences were detected in alpha and beta diversity, our study demonstrated several bacterial taxa with abundances that were significantly different across age groups. With young individuals as the reference group, Eggerthella lenta and Bacteroides uniformis were found to be significantly altered in the middle-aged group, while Catenibacterium mitsuokai and Bacteroides plebeius were significantly altered in the elderly group. These age-related differences in the gut microbiome were associated with aberrations in several predicted functional pathways, including dysregulations of pathways related to lipopolysaccharide and tricarboxylic acid cycle in older adults.
The utilization of long-read sequencing facilitated the identification of species- and strain-level differences across age groups, which was challenging with the partial 16S rRNA sequencing approach. Nevertheless, replication studies are warranted to confirm our findings, and if confirmed, further in vitro and in vivo studies are crucial to better understand the impact of the altered levels of age-related bacterial taxa. Additionally, the modest performance of strain-level taxonomic classification using 16S-ITS-23S gene sequences, likely due to the limited depth of currently available alignment databases, highlights the need for optimization and refinement in curating these databases for the long-read sequencing approach.
在过去十年中，与年龄相关的肠道微生物变化已得到广泛研究。此前大多数与年龄相关的微生物组研究是在西方人群中进行的，短读长测序（例如16S V4或V3 - V4区域）是最常用的微生物群分析方法。我们使用长读长测序方法（即针对全长V1 - V9区域的PacBio测序）评估肠道组成差异，以实现更深入的分类分辨率，并更好地表征不同年龄组新加坡人的肠道微生物组。
本研究共纳入83名研究参与者。虽然在α和β多样性方面未检测到显著差异，但我们的研究表明，几个细菌类群的丰度在不同年龄组之间存在显著差异。以年轻人为参照组，发现迟缓埃格特菌和均匀拟杆菌在中年组中显著改变，而三宅链杆菌和普通拟杆菌在老年组中显著改变。肠道微生物组的这些与年龄相关的差异与几个预测功能途径的异常有关，包括老年人中与脂多糖和三羧酸循环相关途径的失调。
长读长测序的应用有助于识别不同年龄组之间物种和菌株水平的差异，这对于部分16S rRNA测序方法来说具有挑战性。然而，需要进行重复研究以证实我们的发现，如果得到证实，进一步的体外和体内研究对于更好地理解与年龄相关细菌类群水平改变的影响至关重要。此外，使用16S - ITS - 23S基因序列进行菌株水平分类的表现一般，这可能是由于当前可用比对数据库的深度有限，凸显了针对长读长测序方法优化和完善这些数据库的必要性。
