| Summary: | Metabolic diseases caused by gene and unhealthy living habits are increasing, which seriously threaten the life of people worldwide. Moreover, the microbiome has been shown to play an active role in the prevention and treatment of metabolic diseases. However, reliable evidence on renalase gene (Rnls), as a common gene related to metabolic diseases, is still lacking with regard to the influence on the microbiome. Hence, we investigated the effect of a normal diet (ND) and a high-fat diet (HFD) on the gut microbiota of Rnls knockout (Rnls<sup>−/−</sup>) and wild-type (Rnls<sup>+/+</sup>) mice. At the end of the 8-week experiment, DNA samples were extracted from fresh feces, and the composition of microbiota was profiled. The species in Rnls<sup>+/+</sup>-ND group were <i>Bifidobacterium pseudolongum</i> and <i>Lactobacillus reuteri</i>. Conversely, the species in Rnls<sup>−/−</sup>-ND group belonged to the genera <i>Lactobacillus</i> and <i>Turicibacter</i>. The HFD changed the ratio of Firmicutes/Bacteroidetes; while the bacteria in the Rnls<sup>+/+</sup>-HFD and Rnls<sup>−/−</sup>-HFD groups were different. Overall, this study not only revealed the composition of microbiota in Rnls<sup>−/−</sup> mice, but also indicated that Rnls and the bacteria related to Rnls may be new candidates in the prevention and diagnosis of metabolic diseases at an early stage.
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