Hematology/Oncology Fellow City of Hope Comprehensive Cancer Center Duarte, CA, United States
Background: Sarcopenia, defined as loss of skeletal muscle mass, is associated with inferior outcomes in metastatic renal cell carcinoma (mRCC). Herein, we investigate the role of gut microbial metabolic pathways on the development of sarcopenia in mRCC.
Methods: Patients with mRCC that had an investigational stool collection and a prior computed tomography scan were included. Axial images of the L3 vertebral segment were identified from three consecutive scans. SliceOMatic software was used to estimate the muscle mass area on each image. The mean skeletal muscle area was normalized for squared height (cm2/m2), with patients being classified as sarcopenic or non-sarcopenic, based on validated reference values for males and females. Stool microbial profiles were analyzed using MetaPhlAn 3.0. Functional pathways associated with particularly abundant microbiota in relation to sarcopenia (measured by LDA effect size analysis) were identified using the HUMAnN 3.0 platform.
Results: In total, 62 patients met criteria for inclusion (45:17 M:F). The median age was 69 (range 33-93) and predominantly of White race (64.6%). The majority histology was clear cell (88.7%). A total of 27 patients were sarcopenic, while 35 were non-sarcopenic. Parabacteroides distasonis, and Dialister species were associated with sarcopenia to the greatest degree, with LDA scores >3. In contrast, Bacteroides vulgatis, Collinsella aerofaciens, Streptococcaceae species, and Monoglobius species were associated with the absence of sarcopenia. Distinct metabolic pathways, in particular gluconeogenesis I (P=0.009), methanogenesis from acetate (P=0.041), and pathway 7254 of TCA cycle VII (P=0.041) were significantly associated with sarcopenia. In contrast, the colanic acid/M antigen pathway was negatively associated with sarcopenia (P=0.033).
Conclusions: Distinct bacterial populations appear to express metabolic pathways associated with a catabolic state in mRCC patients with sarcopenia.
