DataSheet1_Genetics causal analysis of oral microbiome on type 2 diabetes in East Asian populations: a bidirectional two-sample Mendelian randomized study.docx

IntroductionThe dysbiosis of the oral microbiome is associated with the progression of various systemic diseases, including diabetes. However, the precise causal relationships remain elusive. This study aims to investigate the potential causal associations between oral microbiome and type 2 diabetes (T2D) using Mendelian randomization (MR) analyses.
MethodsWe conducted bidirectional two-sample MR analyses to investigate the impact of oral microbiome from saliva and the tongue T2D. This analysis was based on metagenome-genome-wide association studies (mgGWAS) summary statistics of the oral microbiome and a large meta-analysis of GWAS of T2D in East Asian populations. Additionally, we utilized the T2D GWAS summary statistics from the Biobank Japan (BBJ) project for replication. The MR methods employed included Wald ratio, inverse variance weighting (IVW), weighted median, MR-Egger, contamination mixture (ConMix), and robust adjusted profile score (RAPS).
ResultsOur MR analyses revealed genetic associations between specific bacterial species in the oral microbiome of saliva and tongue with T2D in East Asian populations. The MR results indicated that nine genera were shared by both saliva and tongue. Among these, the genera Aggregatibacter, Pauljensenia, and Prevotella were identified as risk factors for T2D. Conversely, the genera Granulicatella and Haemophilus D were found to be protective elements against T2D. However, different species within the genera Catonella, Lachnoanaerobaculum, Streptococcus, and Saccharimonadaceae TM7x exhibited multifaceted influences; some species were positively correlated with the risk of developing T2D, while others were negatively correlated.
DiscussionThis study utilized genetic variation tools to confirm the causal effect of specific oral microbiomes on T2D in East Asian populations. These findings provide valuable insights for the treatment and early screening of T2D, potentially informing more targeted and effective therapeutic strategies.

引言 口腔微生物群失调与包括糖尿病在内的多种全身性疾病的进展相关，但确切的因果关联仍不明确。本研究旨在通过孟德尔随机化（Mendelian randomization, MR）分析，探究口腔微生物群与2型糖尿病（type 2 diabetes, T2D）之间的潜在因果关联。
方法 我们开展双向双样本孟德尔随机化分析，以探究唾液与舌部口腔微生物群对2型糖尿病的影响。本分析基于口腔微生物群的宏基因组全基因组关联研究（metagenome-genome-wide association studies, mgGWAS）汇总统计量，以及东亚人群2型糖尿病全基因组关联研究的大型荟萃分析结果。此外，我们还使用日本生物样本库（Biobank Japan, BBJ）项目的2型糖尿病全基因组关联研究汇总统计量进行重复验证。本研究采用的孟德尔随机化方法包括沃尔德比率（Wald ratio）、逆方差加权（inverse variance weighting, IVW）、加权中位数、MR-Egger、污染混合模型（contamination mixture, ConMix）以及稳健调整轮廓得分（robust adjusted profile score, RAPS）。
结果 我们的孟德尔随机化分析显示，东亚人群唾液与舌部口腔微生物群中的特定细菌类群与2型糖尿病存在遗传关联。分析结果表明，唾液与舌部共享9个菌属。其中，聚集杆菌属（Aggregatibacter）、Pauljensenia属以及普雷沃菌属（Prevotella）被鉴定为2型糖尿病的危险因素；反之，颗粒链菌属（Granulicatella）以及嗜血杆菌属D群（Haemophilus D）被发现是2型糖尿病的保护因素。而在Catonella属、Lachnoanaerobaculum属、链球菌属（Streptococcus）以及Saccharimonadaceae TM7x科中，不同菌种的作用存在多面性：部分菌种与2型糖尿病发病风险呈正相关，其余则呈负相关。
讨论 本研究利用遗传变异工具，证实了东亚人群中特定口腔微生物群对2型糖尿病的因果效应。上述研究结果为2型糖尿病的治疗与早期筛查提供了有价值的参考，有望助力开发更具针对性与有效性的治疗策略。