Abnormal Bile Acid Metabolism is an Important Feature of Gut Microbiota and Fecal Metabolites in Patients with Slow Transit Constipation

Abstract

Background: Destructions in the intestinal ecosystem are implicated with changes in slow transit constipation (STC), which is a kind of intractable constipation characterized by colonic motility disorder. However, the role of gut microbes in the pathophysiology of STC and deep relationships between the gut microbiota and fecal metabolites have not been understood. Methods: Fecal samples of 30 patients suffering from STC and 30 healthy subjects were performed 16S rDNA amplicon sequencing and metabolomics to obtain evidence of distinct phenotypes of fecal microorganisms and metabolites. The relationship between fecal microorganisms, metabolites, and clinical manifestations was explored according to the correlation analysis. Findings: The α-diversity of the STC group was changed to a certain degree, and the β-diversity was significantly different, which indicated that the composition of the gut microbiota of STC patients was inconsistent with healthy subjects. Different metabolites between STC and control group were involved in the process of bile acids and lipid metabolism. The colon histomorphology of STC patients was significantly disrupted, and TGR5 and FXR were significantly down-regulated. The differences in metabolites were related to changes in the abundance of specific bacteria and patients' intestinal dysfunction. Analysis of the fecal genomics and metabolomics enabled separation of the STC from controls based on random forest model prediction (STC vs control (14 gut microbiota and metabolite biomarker s) – Sensitivity: 1, Specificity: 0.877) Interpretation: Abnorma fecal microorganisms and metabolites related to bile acid metabolism is characteristic of STC, which provided a perspective for the diagnosis and intervention of STC. Funding: This work was supported by the National Key R&D Program of China (2018YFC1706506), Foundation of Tianjin Municipal Health Commission (No. ZC20097), Foundation of Tianjin Union Medical Center (No. 2020YJ017, 2017YJZD005), and National Natural Science Foundation of China (No. 82174374). Declaration of Interest: All authors declare that they do not have any competing interests. Ethical Approval: This study was conducted in Tianjin Union Medical Center, Tianjin, China. The samples and clinical data used in this study were obtained with approval of institutional review boards and under conditions of informed consent (China Clinical Trial Registry, ChiCTR2000033227).