In this schematic representation of the study, we highlight for each step the research question we want to answer, the analysis workflow, and the data used. We first aimed to estimate how much of the variance in serum and fecal bile acids is explained by the host genome, the gut microbiome, and diet in the TwinsUK and ZOE PREDICT-1 cohorts (step 1). We then investigated which primary and secondary bile acids are correlated with post-prandial lipemia, inflammation, and liver function in ZOE PREDICT-1 and replicated the top hit in the BARIA study (step 2). Finally, we further identified the gut microbiome and dietary features correlating with the BA (isoUDCA) associated with post-prandial lipemia, inflammation, and liver function in TwinsUK and ZOE PREDICT-1 (step 3) and determined how much dietary intervention (Omega-3 and Fiber Intervention to Improve Metabolic Health study) and bariatric surgery (BARIA study) affect its circulating levels.
