Exploring serum bile acid variability: population-based concentration ranges and impact of lifestyle factors in an adult population

Abstract Objectives Bile acids (BAs) play crucial roles in digestion and metabolic regulation, and their composition is increasingly recognised as relevant to health and disease. This study aimed to establish population-based concentration ranges (2.5th–97.5th percentiles) for 24 individual serum BAs and assess the influence of demographic and lifestyle factors in a large cohort of Swedish adults. Methods Serum samples from 931 Swedish adults were analysed using liquid chromatography–high-resolution mass spectrometry. Population-based concentration ranges were calculated for individual BAs, and associations with sex, age, BMI, sampling time, smoking, Swedish snuff use, serum cotinine, alcohol consumption, and ancestry were evaluated. Results We found extensive interindividual variability in BA concentrations. The most abundant BAs were glycine-conjugated forms, while primary unconjugated BAs exhibited the largest concentration ranges, differing by over 1,000-fold between individuals. Sex-specific patterns emerged, with men showing significantly higher levels of unconjugated BAs. Age and BMI were negatively associated with taurine-conjugated BAs, and weak time-of-day variations were observed for several conjugated BAs. Lifestyle factors such as smoking, assessed through self-report and serum cotinine, showed stronger associations with BA levels than alcohol or ancestry, notably with increased murideoxycholic acid (MDCA) and reduced conjugated BA levels among nicotine users. Conclusions These findings provide robust serum concentration ranges and highlight key variables that may confound BA biomarker interpretations, emphasising the need to consider sex, age, BMI, and lifestyle in future clinical and epidemiological applications.