Co‐occurrence of gut microbiota dysbiosis and bile acid metabolism alteration is associated with psychological disorders in Crohn's disease

Abstract

This study aims to elucidate the relationships between gut microbiota, bile acid metabolism, and psychological comorbidity in Crohn's disease (CD). We profiled the fecal microbiota composition and quantified the bile acid pool of 39 CD patients and 14 healthy controls using 16S rRNA gene sequencing and liquid chromatography–tandem mass spectrometry, respectively. 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 of 7‐DHCA was particularly higher in the serum of CD patients with psychological disorders. The fecal levels of HDCA and 12‐DHCA of the CD patients were inversely correlated with their Self‐Rated Depression Scale (SDS) scores, whereas the serum level of 7‐DHCA was positively correlated with the SDS scores. In addition, the fecal levels of TDCA, TLCA, and TβMCA showed a positive correlation with the Self‐Rated Anxiety Scale (SAS) scores. 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. In addition, the overabundant Enterobacteriaceae and Lachnospiraceae in CD patients may contribute to psychological comorbidity via dysregulating their bile acids metabolism. 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.

Causality of genetically determined metabolites on anxiety disorders: a two-sample Mendelian randomization study

“…Studies have proved that primary bile acid metabolites/pathways are involved in several aspects of brain function and behavior [ 46 ]. Moreover, it has been reported that changes in the gut microbiota composition may be associated with alterations in the primary bile acid metabolism that are involved in the biological process of psychological disorders in Crohn’s disease [ 47 ]. A traditional Chinese medicine cohort revealed that amino acid metabolism, such as cysteine and methionine metabolism, might be involved in brain health disorders characterized by alterations in evaluation of bile acid biosynthesis [ 48 ].…”

Bile acids in immunity: Bidirectional mediators between the host and the microbiota

“…Finally, given bidirectional interactions between host/microbe-derived bile acids and the microbiome, it is not surprising that the bile acid pool is altered in dysbiosis. For example, patients suffering from inflammatory bowel disease (IBD) were reported to have decreased concentrations of secondary BAs in feces and serum ( 21 , 22 ). Given the above, it is tempting to speculate if BA supplementation could improve dysbiosis in IBD patients.…”

“…On the final note, the differences in BA pool in disease may not only be quantitative but also qualitative. For example, IBD patients had impaired desulfation of BAs, which resulted in increased levels of 3-OH-sulphated BA metabolites that lack anti-inflammatory potential ( 21 , 22 ). Collectively, bile acids, first produced by the host, and later modified by the microbiota, constitute a unique class of compounds active along the host-to-microbe, and microbe-to microbe axes, that ultimately shapes the microbiota composition of the host ( Figure 1A , Table 1 ).…”

The clinical and mechanistic roles of bile acids in depression, Alzheimer's disease, and stroke

“…In a study of patients with Crohn's disease (CD), Feng et al. also noticed that GCA was positively correlated with both Zung's Self‐Rated Anxiety Scale (SAS) and Self‐Rated Depression Scale (SDS) [55], which means that a higher risk of depression accompanied with higher serum level of GCA in CD patients. However, another mice study has opposite outcome that blood CA was significantly increased in the restraint box‐induced mouse models [56].…”