BACKGROUND Diet is a major factor influencing the composition and metabolic activity of the gut microbiota. OBJECTIVE This study investigated the effect of soy compared with dairy protein on the gut microbiota of hamsters to determine whether changes in microbiota could account for soy protein's lipid lowering properties. METHODS Thirty-two 6- to 8-wk-old, male Golden Syrian hamsters were fed a Western diet containing 22% (%wt) milk protein isolate (MPI) as the single protein source for 3 wk followed by 6 wk of one of 4 diets containing either [22% protein (%wt)]: MPI, soy protein concentrate (SPC), partially hydrolyzed soy protein isolate (SPI1), or intact soy protein isolate. Serum lipids, hepatic gene expression, and gut microbial populations were evaluated. RESULTS Serum total and LDL-cholesterol concentrations were lower in the SPC-fed group (183 ± 9.0 and 50 ± 4.2 mg/dL, respectively) than in the MPI group (238 ± 8.7 and 72 ± 3.9 mg/dL, respectively) (P< 0.05). Triglyceride (TG) concentrations were lower (P< 0.05) in the SPI1-fed group (140 ± 20.8 mg/dL) than in the MPI-fed group (223 ± 14.2 mg/dL). VLDL and non-HDL-cholesterol concentrations were lower (by 40-49% and 17-33%, respectively) in all soy-fed groups than in the MPI-fed group (P< 0.05). Sequencing of the 16S ribosomal RNA gene revealed greater microbial diversity in each soy-fed group than in the MPI-fed group (P< 0.05). The cholesterol- and TG-lowering effect of soy protein was associated with higher expression of 3-hydroxy-3-methylglutaryl-CoA reductase (Hmgcr), lanosterol synthase (Lss), and farnesyl-diphosphosphate farnesyl-transferase 1 (Fdft1) (1.6-2.5-fold higher), and lower steroyl-CoA desaturase-1 (Scd1) expression (37-46% lower) in all soy-fed groups (P< 0.05) compared with the MPI-fed group. Gut microbes that showed significant diet differences were significantly correlated (ρ = -0.68 to 0.65,P< 0.05) with plasma lipids and hepatic gene expression. CONCLUSION Dietary protein sources in male Golden Syrian hamsters fed a Western diet affect the gut microbiota, and soy protein may reduce lipogenesis through alterations of the gut microbial community.
