Periodontitis relates to benign prostatic hyperplasia via the gut microbiota and fecal metabolome

Abstract

Objectives: Periodontitis is associated with benign prostatic hyperplasia (BPH), whether it related to gut floramicrobiota and metabonomics is unclear.

Methods: We established ligature-induced periodontitis (EP), testosterone-induced BPH, and composite rat models. Fecal samples were collected to detect gut microbiota by 16S rDNA sequencing and metabonomics were detected by liquid chromatography tandem mass spectrometry (LC-MS/MS).

Results: Sequencing results revealed differential gut floramicrobiota composition between EP+BPH group and other three groups. The abundances of Ruminococcus flavefaciens were significantly increased in EP+BPH group compared with other groups. Tenericutes, Mollicutes, RF39 and Ruminococcus gnavus were significantly decreased in EP+BPH group compared with BPH group, while Ruminococcus callidus and Escherichia were significantly decreased compared with EP group. For gut metabonomics, LC-MS/MS showed that fecal metabolites and seven metabolic pathways were changed in EP+BPH group, such as biosynthesis of unsaturated fatty acids, steroid hormone biosynthesis. Correlation analysis showed that the alterations of gut metabolism were significantly correlated with differential gut floramicrobiota, such as Ruminococcus callidus and Ruminococcus flavefaciens.

Conclusion: Our study highlights the relationship of periodontitis and BPH, the alterations of gut floramicrobiota and metabolites may be involved in two diseases, which provides new idea for prevention and treatment of patients with periodontitis concurrent BPH.

Keywords: benign prostatic hyperplasia; fecal metabolites; gut microbiota; multi-omics analysis; periodontitis.

Figure 1

Effect of EP + BPH on the gut microbiota was different from that of EP or BPH (A) Grouping and comparison strategies: we divided all the rats into four groups (control group, EP group, BPH group, and EP + BPH group) and compared between groups. BPH/Control represents the effect of BPH on healthy control rats, EP/Control represents the effect of EP on healthy control rats, EP + BPH/EP represents the effect of BPH on EP + BPH rats, and EP + BPH/BPH represents the effect of EP on EP + BPH rats. (B) Overview of OTUs in different groups: different colors represent different groups, and the overlapping parts of the numbers are common. Principal component analysis (PCA) (C), partial least squares discrimination analysis (PLS-DA) (D), and principal co-ordinates analysis (PCoA) (E) for different groups: different colors represent different groups. (F) The clustering tree of the unweighted pair-group method with arithmetic means (UPGMA): for samples under the same branch, the shorter the branch length between samples, the more similar the two samples are, and the higher the similarity of species composition is.

Figure 2

EP + BPH affects the structure of gut microbiota. The species bar chart shows the species composition and proportion of each sample at family level (A) and genus level (B): The X axis is the sample name, and the Y axis is the relative abundance of annotated microbiota species.

Figure 3

EP + BPH affects the abundance of gut microbiota, which is different from EP or BPH. Comparison of relative abundance of Tenericutes (A), Mollicutes (B), RF39 (C), Ruminococcus callidus (D), Roseburia (E), Ruminococcus (F), Dorea (G), Escherichia coli (H), and Ruminococcus gnavus (I) in different groups. ^* p < 0.05, ^** p < 0.01, ^*** p < 0.001.

Figure 4

EP and BPH may affect fecal metabolites through interaction in rats. (A) Principal component analysis (PCA) for different groups: different colors represent different groups. Petal diagram of metabolites (B) and metabolic pathways (C) in different comparison pairs: different colors represent different pairs, and the overlapping parts of the numbers are common. (D) Intersection of different functional enrichment pathways.

Figure 5

Alteration in metabolites in metabolic pathways that may be related to the interaction between EP and BPH. Alteration of related metabolites in the biosynthesis of unsaturated fatty acids (A), steroid hormone biosynthesis (B), nicotinate and nicotinamide metabolism (C), tyrosine metabolism (D), primary bile acid biosynthesis (E), prostate cancer (F), and pathways in cancer (G).

Figure 6

Changes in gut microbiota are correlated with the changes in metabolites. Heat map of correlations between gut microbiota and metabolites in metabolic pathways: X axis is the changed gut microbiota, and the Y axis is the metabolites in the metabolic pathway. ^* p < 0.05, ^** p < 0.01.