Alterations of oral microbiota and impact on the gut microbiome in type 1 diabetes mellitus revealed by multi-omic analysis

Background Alterations of the gut microbiome have been linked to multiple chronic diseases. However, the drivers of such changes remain largely unknown. The oral cavity acts as a major route of exposure to exogenous factors including pathogens, and processes therein may affect the communities in the subsequent compartments of the gastrointestinal tract. Here, we perform strain-resolved, integrated multi-omic analyses of saliva and stool samples collected from eight families with multiple cases of type 1 diabetes mellitus (T1DM). Results We identified distinct oral microbiota mostly reflecting competition between streptococcal species. More specifically, we found a decreased abundance of the commensal Streptococcus salivarius in the oral cavity of T1DM individuals, which is linked to its apparent competition with the pathobiont Streptococcus mutans. The decrease in S. salivarius in the oral cavity was also associated with its decrease in the gut as well as higher abundances in facultative anaerobes including Enterobacteria. In addition, we found evidence of gut inflammation in T1DM as reflected in the expression profiles of the Enterobacteria as well as in the human gut proteome. Finally, we were able to follow transmitted strain-variants from the oral cavity to the gut at the metagenomic, metatranscriptomic and metaproteomic levels, highlighting not only the transfer, but also the activity of the transmitted taxa along the gastrointestinal tract. Conclusions Alterations of the oral microbiome in the context of T1DM impact the microbial communities in the lower gut, in particular through the reduction of “oral-to-gut” transfer of Streptococcus salivarius. Our results indicate that the observed oral-cavity-driven gut microbiome changes may contribute towards the inflammatory processes involved in T1DM. Through the integration of multi-omic analyses, we resolve strain-variant “mouth-to-gut” transfer in a disease context.

研究背景：肠道微生物组（gut microbiome）的改变与多种慢性疾病存在关联，但此类菌群改变的驱动因素目前仍未明确。口腔是包括病原体在内的外源性因素暴露的主要途径，口腔内的生理与微生态过程可能影响胃肠道后续区段的微生物群落。本研究对8个存在多例1型糖尿病（type 1 diabetes mellitus, T1DM）患者的家庭采集的唾液与粪便样本，开展了菌株分辨率的整合多组学分析。
研究结果：我们鉴定出具有显著差异的口腔微生物群，其差异主要反映了链球菌属物种间的竞争关系。具体而言，1型糖尿病患者口腔内的共生唾液链球菌（Streptococcus salivarius）丰度降低，这与其与致病共生菌变形链球菌（Streptococcus mutans）的明显竞争密切相关。口腔内唾液链球菌的减少不仅与其肠道内该菌丰度降低存在关联，同时还伴随包括肠杆菌科（Enterobacteria）在内的兼性厌氧菌丰度升高。此外，我们在1型糖尿病患者中发现了肠道炎症的相关证据，该证据可通过肠杆菌科的基因表达谱以及人类肠道蛋白质组体现出来。最终，我们能够在宏基因组学（metagenomic）、宏转录组学（metatranscriptomic）以及宏蛋白质组学（metaproteomic）层面，追踪从口腔传播至肠道的菌株变异体，不仅证实了微生物类群的跨区段转移，还揭示了这些传播类群在胃肠道内的代谢活性。
结论：1型糖尿病背景下的口腔微生物组改变会影响下肠道的微生物群落，尤其是通过降低唾液链球菌的"口-肠"传播效率实现。本研究结果表明，经口腔驱动的肠道菌群改变可能参与了1型糖尿病相关的炎症进程。通过整合多组学分析，我们在疾病场景下解析了菌株变异体的"口-肠"传播过程。