Hypercholesterolemia is a common metabolic syndrome in modern human society. Despite that the alteration of host gut microbiota has been linked to hypercholesterolemia in previous studies, the key host-microbiota interaction of hypercholesterolemia remains elusive. Lactobacillus paracasei subsp. paracasei NTU 101 (NTU 101) and deep sea water (DSW) were known for cholesterol-lowering potential. The impact of NTU 101 and DSW on hamster gut microbiota was investigated side-by-side using denaturing gradient gel electrophoresis (DGGE) and metagenomic analysis in this study. These two cholesterol-lowering substances altered hamster cecal microbiota in a very different way with similar cholesterol-lowering effects. Bacteroidetes was the only bacterial population that significantly correlated to host lipid profile (serum total cholesterol and serum low-density lipoprotein). Allobaculum and Clostridium XIVa were associated with beneficial effect of NTU 101. Parasutterella was only associated with consumption of DSW. The major bacterial taxa Akkermansia is associated with high-cholesterol diet but not host cholesterol level. This phenomenon suggested that cholesterol-lowering effect is not necessarily linked to specific bacteria-host interaction, and the conclusion of causal relationships among bacterial abundance, diet, and host physiology should be more rigorously investigated.