Reproducibility, Temporal Variability, and Concordance of Serum and Fecal Bile Acids and Short Chain Fatty Acids in a Population-Based Study
Zeinab Farhat, Joshua N. Sampson, Allan Hildesheim, Mahboobeh Safaeian, Carolina Porras, Bernal Cortés, Rolando Herrero, Byron Romero, Emily Vogtmann, Rashmi Sinha, Erikka Loftfield
Abstract
BACKGROUND: Bile acid (BA) and short chain fatty acid (SCFA) production is affected by diet and microbial metabolism. These metabolites may play important roles in human carcinogenesis. METHODS: We used a fully quantitative targeted LC-MS/MS system to measure serum and fecal BA and SCFA concentrations in 136 Costa Rican adults at study baseline and 6-months. We randomly selected 50 participants and measured their baseline samples in duplicate. Our objective was to evaluate: Technical reproducibility; 6-month temporal variability; and concordance between sample type collected from the same individual at approximately the same time. RESULTS: Technical reproducibility was excellent, with intraclass correlation coefficients (ICC) ≥0.83 for all BAs except serum tauroursodeoxycholic acid (ICC = 0.72) and fecal glycolithocholic acid (ICC = 0.66) and ICCs ≥0.81 for all SCFAs except serum 2-methylbutyric acid (ICC = 0.56) and serum isobutyric acid (ICC = 0.64). Temporal variability ICCs were generally low, but several BAs (i.e., deoxycholic, glycoursodeoxycholic, lithocholic, taurocholic, and tauroursodeoxycholic acid) and SCFAs (i.e., 2-methylbutyric, butyric, propionic, and valeric acid) had 6-month ICCs ≥0.44. The highest degree of concordance was observed for secondary and tertiary BAs. CONCLUSIONS: Serum and fecal BAs and SCFAs were reproducibly measured. However, 6-month ICCs were generally low, indicating that serial biospecimen collections would increase statistical power in etiologic studies. The low concordance for most serum and fecal metabolites suggests that consideration should be paid to treating these as proxies. IMPACT: Our findings will inform the design and interpretation of future human studies on associations of BAs, SCFAs, and potentially other microbial metabolites, with disease risk.