| BACKGROUND:The Human Microbiome Project and the emergence of human intestinal met agenome have opened up a new perspective for the study of human microbiome.Human gut microbiota has attracted much attention because of its special clinical significance.In the process of host health and diseas e,gut microbiota plays an important role.The occurrence and development of gut microbiota are inseparabl e and interdependent with endocrine,immune,metabolic pathways and the development and maturation of the body.Intestinal flora not only mediates the production of a variety of harmful substances,but also cause s damage to the host by affecting the absorption,immunity,metabolism and other pathways of nutrients.St udies have found that a variety of diseases are related to intestinal flora imbalance.Recent studies have rep orted that periodontitis and benign prostatic hyperplasia(BPH)are associated with alterations in gut microb iota and metabolomics,respectively.Many evidences also suggest that periodontitis is associated with BPH.At present,it is not clear whether there is an association between gut microbiota and periodontitis with BPH and the potential mechanism of association.OBJECTIVES: Through animal experiments,this study analyzed the changes in the compositio n and abundance of intestinal flora and intestinal metabolites to reveal the correlation between periodontitis and BPH through intestinal flora and fecal metabolomics,and to find out the flora,metabolites and key sig naling pathways mediating the two diseases,to improve the understanding of the correlation between perio dontitis and BPH.This study provides new ideas for the combined diagnosis and treatment of periodontitis and BPH in the future.To improve the understanding of the correlation between periodontitis and BPH fro m the perspective of gut microbiota,and to provide new ideas for the prevention and treatment of periodont itis and BPH.METHODS: Twenty SPF male Sprague-Dawley rats(7 weeks old)were selected and randomly divided into experimental periodontitis(EP)group,BPH group,EP+BPH group and healthy control group after one week of adaptive feeding.The EP model was induced by ligating the bilateral maxillary first and s econd molars.The BPH rat model was established by subcutaneous injection of testosterone propionate afte r castration.The model of the compound group was established by ligation of bilateral maxillary first and s econd molars and castration followed by subcutaneous injection of testosterone propionate.The healthy con trol group did not receive any treatment.Four weeks later,the rats were sacrificed under anesthesia with an intraperitoneal overdose of sodium pentobarbital.Fecal samples were collected under sterile operation for 16 S sequencing and mass spectrometry detection of intestinal flora.The prostate tissue samples were separat ed,the wet weight of the prostate tissue was measured,fixed with 4% paraformaldehyde,and subsequently made tissue sections for staining.The DNA of the microbiota was extracted for PCR amplification and libr ary construction.After 16 S sequencing,the abundance,species composition,α diversity and β diversity of t he microbiota were analyzed,and the biological functions of the microbiota were predicted.At the same ti me,the treated fecal samples were detected by liquid chromatography mass spectrometry(LC-MS/MS)to a nalyze the differential metabolites,metabolic pathways,and functional enrichment analysis.Finally,the cor relation between gut microbiota and differential metabolites and metabolic pathways was analyzed.MOTH UR(v1.31.2),QIIME(v1.8.0),UCHIME(v4.2.40),RDP classifier(v.2.2)and R software were used for dat a processing and analysis.RESULTS: 16 S sequencing results showed significant differences in gut microbiota composition between the EP+BPH group and the other three groups.The abundance of Ruminococcus flavefaciens in E P+BPH group was significantly increased.The numbers of Tenericutes,Mollicutes,Ruminococcus gnavus and RF39 in EP+BPH group were significantly lower than those in BPH group.Ruminococcus callidus and Escherichia were significantly lower in the EP+BPH group than in the EP group.Significant differences in gut metabolites and metabolic pathways were found among the four groups by LC-MS/MS analysis.The d ifferential metabolites were mainly involved in cell process,environmental information processing,lipid m etabolism,amino acid metabolism and other functional pathways,involving the digestive system,circulator y system,sensory system,nervous system and immune system of the body.Further enrichment analysis sho wed that the differential metabolites in EP+BPH group were changed in 7 metabolic pathways,such as uns aturated fatty acid biosynthesis,steroid hormone biosynthesis,niacin and nicotinamide biosynthesis,tyrosi ne metabolism,primary bile acid biosynthesis,and prostate cancer carcinogenic pathway.Analysis of the c orrelation between intestinal flora and intestinal metabolites and their metabolic pathways showed that The changes of metabolites were significantly correlated with the differences in Escherichia,Erysipelotrichacea e,Erysipelotrichales,Mollicutes,Tenericutes,RF39,Peptostreptococcaceae,Paraprevotella,Ruminococcu s gnavus,Ruminococcus callidus and Ruminococcus flavefaciens(P < 0.05).CONCLUSIONS: Our study highlights the relationship between periodontitis and BPH,and the changes of gut microbiota and metabolites may be involved in the interaction between the two diseases,wh ich provides new ideas for the prevention and treatment of BPH patients with periodontitis.In the future,fu rther studies are needed to clarify the potential mechanism and causal relationship between the interaction o f gut microbiota and metabolites in the two diseases.Our study confirmed that the alteratioin of gut microbi ota and its metabolites may be involved in the interaction between periodontitis and BPH,which provides a new way to understand the relationship between periodontitis and BPH,while further studies are needed to clarify the mechanism of gut microbiota and metabolites in the future. |
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