Study on alterations of physiological functions in aged constipation rats with fluid-deficiency based on metabonomic and microbiology analysis

摘要

Constipation, a common and complex clinical symptom, is a predisposing factor for many serious diseases, such as gastrointestinal diseases, cardiovascular diseases and cancers. Some reports suggest that constipation is associated with gut microbiota, but the specific mechanism is unknown. To clarify how constipation interferes with the normal physiological function of organisms, H-1 NMR profiles combined with polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE) and 16s rRNA gene sequencing were used to investigate the relationship among constipation, metabolism of gut microbiota and host. 27 urinary metabolites and 22 faecal metabolites were found to be associated with constipation, which affect the metabolism of energy, butyric acid, choline, amino acid and the functions of liver and kidney. 5 biomarkers were screened to diagnose the constipation based on the receiver operating characteristic (ROC) analysis. Meanwhile, the levels of Lactobacillus, Intestinimonas, Muribaculum, Eubacterium were significantly decreased, whereas levels of Actinomyces, Culturomica, Ruminococcus, Prevotella, Ruminiclostridium and Acinetobacter were significantly increased. Moreover, the above altered microbiota showed a strong correlation with the metabolites of short chain fatty acids, amino acids, bile acids, choline, and the intermediate product of tricarboxylic acid cycle. These results implied that constipation could result in intestinal dysbacteriosis and metabolism disorder, thereby affecting some normal physiological functions in host. The relationship between gut microbiota and metabolites revealed the potential hazard of constipation from the perspectives of metabonomic and microbiology, and provided new avenues for the diagnosis of constipation and potential drug targets in preventing related diseases.