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It is unclear how high fructose consumption induces disparate metabolic responses in genetically diverse mouse strains. We aimed to investigate whether the gut microbiota contributes to differential metabolic responses to fructose. Eight-week-old male C57BL/6J (B6), DBA/2J (DBA), and FVB/NJ (FV mice were given 8% fructose solution or regular water (control) for 12 wk. The gut microbiota composition in cecum and feces was analyzed using 16S ribosomal DNA sequencing, and permutational multivariate ANOVA (PERMANOVA) was used to compare co