摘要Background: Studies had shown many diseases affect the stability of human microbiota, but how this relates to benign prostatic hyperplasia (BPH) has not been well understood. Hence, this study aimed to investigate the regulation of BPH on gut microbiota composition and metabonomics. Methods: We analyzed gut samples from rats with BPH and healthy control rats, the gut microbiota composition and metabonomics were detected by 16S rDNA sequencing and liquid chromatography tandem mass spectrometry (LC– MS/MS). Results: High-throughput sequencing results showed that gut microbiota beta-diversity increased (P<0.01) in the BPH group vs. control group. Muribaculaceae (P<0.01), Turicibacteraceae (P<0.05), Turicibacter (P<0.01) and Coprococcus (P<0.01) were significantly decreased in the BPH group, whereas that of Mollicutes (P<0.05) and Prevotella (P<0.05) were significantly increased compared with the control group. Despite profound interindividual variability, the levels of several predominant genera were different. In addition, there were no statistically significant differences in several bacteria. BPH group vs. control group: Firmicutes (52.30％ vs. 57.29％, P>0.05), Bacteroidetes (46.54％ vs. 41.64％, P>0.05), Clostridia (50.89％ vs. 54.66％, P>0.05), Ruminococcaceae (25.67％ vs. 20.56％, P>0.05). LC–MS/MS of intestinal contents revealed that differential metabolites were mainly involved in cellular processes, environmental information processing, metabolism and organismal systems. The most important pathways were global and overview maps, lipid metabolism, amino acid metabolism, digestive system and endocrine system. Through enrichment analysis, we found that the differential metabolites were significantly enriched in metabolic pathways, steroid hormone biosynthesis, ovarian steroidogenesis, biosynthesis of unsaturated fatty acids and bile secretion. Pearson correlation analysis (R=0.94) showed that there was a strong correlation between Prevotellaceae, Corynebacteriaceae, Turicibacteraceae, Bifidobacteriaceae and differential metabolites. Conclusions: Our findings suggested an association between the gut microbiota and BPH, but the causal relationship between the two groups is unclear. Thus, further studies are warranted to elucidate the potential mechanisms and causal relationships between BPH and gut microbiota.