Reduced Plasma Short-Chain Fatty Acid (SCFA) Concentrations Are Not Associated With Markers of Muscle Health in Non-Small Cell Lung Cancer

Abstract

Abstract Objectives Cancer patients were shown to have an altered intestinal microbiota composition and lower fecal concentrations of the bacterial metabolites short-chain fatty acids (SCFA), which among others serve as energy source to muscle. We previously described an association between reduced plasma SCFA concentrations and muscle dysfunction in chronic wasting diseases and now examined whether this relationship exists in non-small cell lung cancer (NSCLC) patients. Methods We recruited 13 male patients with advanced NSCLC (stage 3–4) without anticancer therapy or surgery in the previous 4 weeks (age: 65.8 [62.2, 69.5] yo, BMI: 27.7 [25.2, 30.2] kg/m2), and 11 healthy male, age-matched controls (age: 68.5 [64.0, 73.0] yo, BMI: 26.5 [24.0, 28.9] kg/m2). Venous plasma was collected in the postabsorptive state to determine SCFA concentrations (in μM) by GC-MS. Nutritional depletion was assessed by unintended weight loss >5% in the past 3 months, muscle mass by DXA, handgrip strength and endurance by dynamometry, and maximal expiratory and inspriratory pressure using a hand-held mouth pressure device. Statistics are by ANCOVA and Pearson's correlation adjusting for age and BMI. Data are mean [95% CI]. Results Acetate (−54.1 [−105.0, −3.1] μmol/L, P = 0.039), propionate (−0.72 [−1.29, −0.16] μmol/L, P = 0.015), and butyrate (−0.52 [−0.92, −0.12] μmol/L, P = 0.014) concentrations were reduced in NSCLC compared to controls. While a higher propionate concentration correlated with a higher life expectancy (P = 0.037), SCFA concentrations were not associated with disease severity (stage 3 vs. 4), presence of nutritional depletion, or cancer type (adenocarcinoma vs. squamous cell carcinoma) (all P > 0.05). We observed no differences in muscle mass, strength or endurance between cancer and healthy participants and SCFA concentrations did not correlate with muscle function and endurance in NSCLC patients (all P > 0.05). Conclusions Our data suggest that the reduced SCFA play a role in overall outcome but not in muscle health in NSCLC patients. Funding Sources AICR, NIH, National Center for Research Resources, Sydney and J.L. Huffines Institute for Sports Medicine and Human Performance.