Alteration of Gut Microbes in Benign Prostatic Hyperplasia Model and Finasteride Treatment Model

Abstract

Gut microbes are closely associated with disease onset and improvement. However, the effects of gut microbes on the occurrence, prevention, and treatment of benign prostatic hyperplasia (BPH) are still unclear. We investigated the alteration of gut microbiota with implications for the diagnosis, prevention, and treatment of BPH and identified correlations among various indicators, including hormone indicators, apoptosis markers in BPH, and finasteride treatment models. BPH induction altered the abundance of Lactobacillus, Flavonifractor, Acetatifactor, Oscillibacter, Pseudoflavonifractor, Intestinimonas, and Butyricimonas genera, which are related to BPH indicators. Among these, the altered abundance of Lactobacillus and Acetatifactor was associated with the promotion and inhibition of prostate apoptosis, respectively. Finasteride treatment altered the abundance of Barnesiella, Acetatifactor, Butyricimonas, Desulfovibrio, Anaerobacterium, and Robinsoniella genera, which are related to BPH indicators. Among these, altered abundances of Desulfovibrio and Acetatifactor were associated with the promotion and inhibition of prostate apoptosis, respectively. In addition, the abundances of Lactobacillus and Acetatifactor were normalized after finasteride treatment. In conclusion, the association between apoptosis and altered abundances of Lactobacillus and Acetatifactor, among other gut microbes, suggests their potential utility in the diagnosis, prevention, and treatment of BPH.

Keywords: Acetatifactor; Lactobacillus; apoptosis; benign prostatic hyperplasia; finasteride; gut microbes.

Figure 1

Microbial diversity in the bacterial community, categorized based on benign prostatic hyperplasia (BPH) and finasteride treatment. Observed operational taxonomic units (OTUs) (a), Shannon index (b), multidimensional scaling (MDS) plot (c), and principal coordinate analysis (PCoA) plot (d) of cecum samples of Wistar rats. Hierarchical clustering of most abundant bacterial families (e) and genera (f) are labeled in the heat map using Spearman’s rank correlation. The groups included: control, injected with corn oil following sham operation; BPH, injected with testosterone undecanoate (125 mg/kg) after castration; BPH+Fina, injected with testosterone undecanoate (125 mg/kg) and finasteride (0.8 mg/kg) after castration.

Figure 2

Alteration of relative bacterial abundance following BPH induction. Comparison between control and BPH groups (a). Significant differences (p < 0.05) were identified using LEfSe based on both the Kruskal−Wallis test (between classes) and the Wilcoxon test (between subclasses). The threshold logarithmic LDA score was 2.5. Correlation analyses between bacterial abundances and BPH indicators (b) or apoptosis markers (c) were conducted. Statistical significance (Spearman’s correlation coefficient): * p < 0.05, ** p < 0.01, and *** p < 0.001.

Figure 3

Alteration of relative bacterial abundances through finasteride treatment. Comparison between BPH and BPH+Fina groups (a). Significant differences (p < 0.05) were identified using LEfSe based on the Kruskal−Wallis test (between classes) and the Wilcoxon test (between subclasses). The threshold logarithmic LDA score was 2.5. Correlation analyses between bacterial abundances and BPH indicators (b) or apoptosis markers (c) were conducted. Statistical significance (Spearman’s correlation coefficient): * p < 0.05, ** p < 0.01, and *** p < 0.001.

Figure 3

Alteration of relative bacterial abundances through finasteride treatment. Comparison between BPH and BPH+Fina groups (a). Significant differences (p < 0.05) were identified using LEfSe based on the Kruskal−Wallis test (between classes) and the Wilcoxon test (between subclasses). The threshold logarithmic LDA score was 2.5. Correlation analyses between bacterial abundances and BPH indicators (b) or apoptosis markers (c) were conducted. Statistical significance (Spearman’s correlation coefficient): * p < 0.05, ** p < 0.01, and *** p < 0.001.

Figure 4

Alteration of relative bacterial abundance due to BPH induction and finasteride treatment. Comparison between control, BPH, and BPH+Fina groups (a). The microbial abundance based on LEfSe analysis is shown in (b–v). Significant differences were identified using LEfSe (p < 0.05) based on both the Kruskal–Wallis test (among classes) and Wilcoxon test (between subclasses). The threshold logarithmic LDA score was 2.5. Statistical analyses were performed using t-test and Mann–Whitney test. ^† p < 0.05, ^†† p < 0.01, and ^††† p < 0.001 compared with control group; * p < 0.05, ** p < 0.01, *** p < 0.001 compared with the BPH group. The groups included: control, injected with corn oil following sham operation; BPH, injected with testosterone undecanoate (125 mg/kg) after castration; BPH+Fina, injected with testosterone undecanoate (125 mg/kg) and finasteride (0.8 mg/kg) after castration.