Dr. A. De Spiegeleer: Department of Geriatrics, Faculty of Medicine and Health Sciences, Ghent University Hospital, C. Heymanslaan 10, 9000 Ghent, Belgium. Tel.: +32 (0) 9 332 84 67, Email:
J Frailty Aging. 2024;13(4):331-340. doi: 10.14283/jfa.2024.75.
The gut microbiome is recognized as a pivotal factor in the pathophysiology of sarcopenia-a condition marked by the accelerated loss of muscle strength, mass and function with ageing. Despite this well-known gut-muscle axis, the potential links between other microbial ecosystems and sarcopenia remain largely unexplored. The oral microbiome has been linked to various age-related health conditions such as rheumatoid arthritis and colorectal cancer. However, its potential association with sarcopenia is unknown. The Saliva and Muscle (SaMu) study seeks to address this knowledge gap.
The SaMu study comprises three sequential phases. In phase 1, a cross-sectional analysis will be conducted on a cohort of 200 individuals aged 70 years or older to examine the relationship between salivary microbiome and sarcopenia status. Participants will be recruited in the three main places of living: general community, assisted living facilities and nursing homes. The salivary microbiome composition will be evaluated utilizing shotgun metagenomics sequencing, while sarcopenia status will be determined through muscle mass (determined by whole-body bioelectrical impedance analysis and calf circumference), muscle strength (grip strength and the 5-times-sit-to-stand test) and physical performance (usual walking speed). In addition to investigating the microbiome composition, the study aims to elucidate microbiome functions by exploring potential omic associations with sarcopenia. To achieve this, salivary proteomics, metabolomics and quorum sensing peptidomics will be performed. Covariates that will be measured include clinical variables (sociodemographic factors, health status, health-related behaviours, oral health and quality of life) as well as blood variables (immune profiling, hormones, kidney and liver function, electrolytes and haematocrit). In phase 2, an in-depth mechanistic analysis will be performed on an envisaged subcohort of 50 participants. This analysis will explore pathways in muscle tissue using histology, genomics and transcriptomics, focusing on (maximal) 25 healthy older adults and (maximal) 25 with severe sarcopenia. Phase 3 involves a two-year clinical follow-up of the initial participants from the cross-sectional analysis, along with a resampling of blood and saliva. Additionally, secondary outcomes like falls, hospitalization and mortality will be examined.
Using a salivary multi-omics approach, SaMu primarily aims to clarify the associations between the oral microbiome and sarcopenia. SaMu is expected to contribute to the discovery of predictive biomarkers of sarcopenia as well as to the identification of potential novel targets to prevent/tackle sarcopenia. This study-protocol is submitted for registration at the ISRCTN registry.
肠道微生物组被认为是肌肉减少症病理生理学的关键因素，肌肉减少症是一种以肌肉力量、质量和功能随着年龄增长而加速丧失为特征的疾病。尽管存在众所周知的肠道-肌肉轴，但其他微生物生态系统与肌肉减少症之间的潜在联系在很大程度上仍未得到探索。口腔微生物组与各种与年龄相关的健康状况有关，如类风湿关节炎和结直肠癌。然而，其与肌肉减少症的潜在关联尚不清楚。唾液和肌肉（SaMu）研究旨在解决这一知识空白。
SaMu 研究包括三个连续阶段。在第 1 阶段，将对 200 名年龄在 70 岁或以上的个体进行横断面分析，以研究唾液微生物组与肌肉减少症状态之间的关系。参与者将在三个主要的居住场所招募：普通社区、辅助生活设施和养老院。将利用 shotgun 宏基因组测序评估唾液微生物组的组成，同时通过全身生物电阻抗分析和小腿围确定肌肉减少症状态，通过握力和 5 次坐站测试确定肌肉力量，通过常规步行速度确定身体机能。除了研究微生物组的组成外，该研究还旨在通过探索与肌肉减少症相关的潜在组学关联来阐明微生物组的功能。为此，将进行唾液蛋白质组学、代谢组学和群体感应肽组学。将测量的协变量包括临床变量（社会人口因素、健康状况、健康相关行为、口腔健康和生活质量）以及血液变量（免疫分析、激素、肾功能、电解质和红细胞压积）。在第 2 阶段，将对预计的 50 名参与者亚组进行深入的机制分析。该分析将使用组织学、基因组学和转录组学研究肌肉组织中的途径，重点关注（最大）25 名健康老年人和（最大）25 名严重肌肉减少症患者。第 3 阶段包括对横断面分析中最初参与者进行为期两年的临床随访，并对血液和唾液进行重新取样。此外，还将检查跌倒、住院和死亡等次要结局。
SaMu 主要采用唾液多组学方法，旨在阐明口腔微生物组与肌肉减少症之间的关联。SaMu 有望发现肌肉减少症的预测生物标志物，并确定预防/治疗肌肉减少症的潜在新靶点。本研究方案在 ISRCTN 登记处注册。
