Hisamatsu Daisuke, Ogata Yusuke, Suda Wataru, Mabuchi Yo, Naraoka Yuna, Yamato Taku, Ikeba Akimi, Kumagai Kyoko, Hattori Masahira, Akazawa Chihiro
Intractable Disease Research Center, Juntendo University Graduate School of Medicine, Tokyo, Japan.
Laboratory for Symbiotic Microbiome Sciences, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
Front Pharmacol. 2025 Apr 7;16:1455753. doi: 10.3389/fphar.2025.1455753. eCollection 2025.
Salivary microbiome alterations are associated with chronic diseases, such as cardiovascular disease, diabetes, and dementia. These chronic diseases often coexist in older adults, leading to polypharmacy. This situation complicates the relationship between systemic diseases and salivary microbiome dysbiosis. Previous studies have demonstrated the association of the human gut microbiome with common prescription drug use, including polypharmacy. However, a comprehensive analysis of the salivary microbiome and prescription drugs is yet to be conducted in older adults. Therefore, in this study, we performed a multivariate analysis to investigate the relationship between salivary microbiomes and host variables, including prescribed drugs, cognitive function, and oral health, in Japanese older adults with different disease backgrounds.
We enrolled non-hospitalised 82 older adults aged ≥70 years from a Japanese village community, and collected metadata, including age, sex, body mass index, cognitive function, oral health, alcohol consumption, smoking, and common prescription drug information. We performed multivariate analyses and functional predictions on the salivary microbiome based on 16S ribosomal RNA gene amplicon sequencing, including the metadata as potential confounders.
We observed a relationship between the human salivary microbiome and prescribed drug use in Japanese older adults with a heterogeneous background of comorbidities. The effects of several prescribed drugs, such as statins, proton pump inhibitors, and transporter/symporter inhibitors, on the salivary microbiome diversity were more prominent than those of host variables, including age, sex, and oral health. Notably, statin use was strongly correlated with a decrease in the abundance. Furthermore, statin intensity and obesity may be associated with altering the salivary microbiome, including functional predictions for vitamin biosynthesis and purine nucleotide degradation pathways in statin users.
Our multivariate analysis, adjusted for prescribed drug use and non-use, revealed the drug-specific alteration of salivary microbiome composition in Japanese older adults with comorbidities. To our knowledge, this study is the first to described the association of common prescription drug use with salivary microbiome alterations in older adults. Our findings indicated that prescribed drug use is a key factor in understanding the link between salivary microbiome changes and systemic diseases in older adults.
唾液微生物群的改变与慢性疾病相关,如心血管疾病、糖尿病和痴呆症。这些慢性疾病在老年人中常同时存在,导致多重用药。这种情况使全身疾病与唾液微生物群失调之间的关系变得复杂。先前的研究已经证明人类肠道微生物群与常见处方药的使用有关,包括多重用药。然而,尚未对老年人的唾液微生物群和处方药进行全面分析。因此,在本研究中,我们进行了多变量分析,以调查不同疾病背景的日本老年人唾液微生物群与宿主变量之间的关系,这些宿主变量包括处方药、认知功能和口腔健康。
我们从一个日本乡村社区招募了82名年龄≥70岁的非住院老年人,并收集了元数据,包括年龄、性别、体重指数、认知功能、口腔健康、饮酒、吸烟和常见处方药信息。我们基于16S核糖体RNA基因扩增子测序对唾液微生物群进行了多变量分析和功能预测,将元数据作为潜在的混杂因素。
我们在具有异质性合并症背景的日本老年人中观察到人类唾液微生物群与处方药使用之间的关系。几种处方药,如他汀类药物、质子泵抑制剂和转运体/同向转运体抑制剂,对唾液微生物群多样性的影响比包括年龄、性别和口腔健康在内的宿主变量更为显著。值得注意的是,使用他汀类药物与丰度降低密切相关。此外,他汀类药物的强度和肥胖可能与唾液微生物群的改变有关,包括对他汀类药物使用者维生素生物合成和嘌呤核苷酸降解途径的功能预测。
我们在调整了处方药使用和未使用情况的多变量分析中,揭示了患有合并症的日本老年人唾液微生物群组成的药物特异性改变。据我们所知,本研究首次描述了常见处方药使用与老年人唾液微生物群改变之间的关联。我们的研究结果表明,处方药的使用是理解老年人唾液微生物群变化与全身疾病之间联系的关键因素。