Here, we show the power of utilizing time series microbiome (16S rRNA amplicon profiling) and metabolome (untargeted liquid chromatography-tandem mass spectrometry [LC-MS/MS]) data to relate two different mouse models of atherosclerosis—ApoE−/− (n = 24) and Ldlr−/− (n = 16)—that are exposed to intermittent hypoxia and hypercapnia (IHH) longitudinally (for 10 and 6 weeks, respectively) to model chronic obstructive sleep apnea. This evidence concerns the gene LDLR and atherosclerosis.