| Background:Patients with Crohn’s disease(CD)may have symptoms of common mental disorders,such as anxiety and depression.Gut microbiota dysbiosis in CD usually leads to an alteration in host metabolism,which may affect the brain-gut axis through signal transduction and immune regulation thereby contributing to depression and anxiety symptoms.Objective:The purpose of this study is to clarify the role of intestinal microbiota and bile acid metabolism in patients with Crohn’s disease and mental disorders(anxiety symptoms or depression symptoms)and their correlation.Methods:Serum and fecal samples were collected from 39 CD patients and 14 healthy controls.The psychological status was accessed using Self-Rated Anxiety Scale(SAS)and Self-Rated Depression Scale(SDS).16 S r RNA gene sequencing was used to profile the fecal microbiota composition.The bile acids(BAs)and short-chain fatty acids(SCFAs)in feces and serum were quantitatively assessed by liquid chromatography tandem mass spectrometry.Results:Alpha-diversity of the fecal microbiota decreased in CD compared with HC(p<0.01).Significant changes in fecal microbiota composition of CD were detected when compared with HC.Especially the relative abundance of SCFA-producing bacteria,including Faecalibacterium,Lachnospira and Roseburia genera.The gut microbiota dysbiosis in CD resulted in an alteration in their metabolism,which may cause depression and anxiety symptoms.According to SAS and SDS scores,39 patients with CD were divided into two groups: the group with psychological disorder(CD-PD,n=14)and the group without psychological disorder(CD-N,n=25).The fecal microbiota biodiversity was particularly declined in CD patients with psychological disorders.An enrichment of Ruminococcus gnavus in CD patients may cause psychological disorders by affecting the microbiota-gut-brain axis via its ability to degrade the gut barrier,regulate the tryptophan-kynurenine metabolism,and modulate bile acid metabolism.And the overabundant Enterobacteriaceae and Lachnospiraceae in CD patients may also contribute to psychological comorbidity via dysregulating their bile acids metabolism.Significant reductions in the secondary bile acids LCA and DCA were found in both the feces and serum samples of CD patients,while the concentration of7-DHCA was particularly higher in the serum of CD patients with psychological disorders.The serum level of 7-DHCA,and fecal levels of HDCA and 12-DHCA showed a positive correlation with the Self-Rated Depression Scale(SDS)score.And the fecal levels of TDCA,TLCA,and T-β-MCA were correlated positively with the Self-Rated Anxiety Scale(SAS)score.In particular,the reduced fecal concentrations of hyodeoxycholic acid and apocholic acid,and increased serum levels of7-dehydrocholic acid in the CD patients were inversely correlated with a higher level of SAS or SDS.Conclusions:The psychological dysfunction of CD patients was closely linked to a shortage of SCFAs and some BAs caused by gut microbiota dysbiosis.Taken together,changes in the gut microbiota composition may cooperate with alterations in the bile acid metabolism that are involved in the development of psychological disorders in CD. |
