Relationship Between Salivary Metabolites and Skeletal Muscle Index in Older Male Patients: A Retrospective Observational Pilot Study to Identify Potential Biomarkers.

Abstract

Background: Nutritional assessment during the perioperative period is critical, particularly for older patients at high risk for complications. Bioelectrical impedance analysis (e.g., InBody) is commonly used to assess skeletal muscle mass via the skeletal muscle index (SMI). However, its use is limited in patients with contraindications, including implantable cardiac devices.

Objective: Therefore, this study explored a noninvasive alternative: assessing the relationship between salivary metabolites and SMI to identify potential biomarkers associated with muscle mass.

Methods: This retrospective study analyzed data from male preoperative patients who had both InBody analysis and salivary metabolomics data collected between January 2021 and March 2024. Salivary metabolites, including butyrate and hexanoate, were quantified using capillary electrophoresis time-of-flight mass spectrometry (CE-TOF MS). Body composition parameters, including SMI, and blood nutritional indicators, were obtained. Volcano plot analysis identified metabolites significantly differing between patients with SMI ≥ 7.0 and < 7.0 kg/m². Receiver operating characteristic (ROC) curve analysis evaluated the discriminatory ability of individual variables. Univariate and multivariate logistic regression analyses identified factors associated with SMI status.

Results: Patients with low SMI were significantly older than those with high SMI. While body composition indices differed significantly, general nutritional blood markers remained comparable. Volcano plot analysis showed significantly higher salivary butyrate and hexanoate levels in patients with SMI ≥ 7.0 kg/m² compared to those with SMI < 7.0 kg/m². ROC curve analysis demonstrated significant discriminatory ability for butyrate, hexanoate, and age. Univariate analysis identified age as significantly associated with SMI status based on odds ratio. Multivariate analysis using stepwise variable selection retained age (OR: 1.155, p-value = 0.070) and hexanoate (OR: 0.980, p-value = 0.269) in the final model.

Conclusions: This exploratory study suggests that salivary metabolites, particularly butyrate and hexanoate, along with age, may serve as potential indicators for discriminating SMI status. These findings suggest the potential utility of salivary metabolites as noninvasive biomarkers for assessing muscle mass in the perioperative setting. This could enable early sarcopenia detection and enhanced nutritional management in older patients, particularly those with contraindications. Trial Registration: UMIN Clinical Trials Registry: UMIN000057185.