Choline deficiency and choline metabolism disorders can lead to anxiety-like behaviors induced by DSS in IBD mice

Abstract

Anxiety and depression caused by inflammatory bowel diseases (IBD) negatively affect the mental health of patients. Emerging studies have demonstrated that the gut-brain axis mediates IBD-induced mood disorders, but the underlying mechanisms of these findings remain unknown. This study unveiled promising evidence that choline dysfunction may be a cause of IBD induced mood disorders. Analysing Dextran Sulfate Sodium Salt (DSS)-induced IBD mice model with transcriptomics and metabolomics technology, it was discovered that mRNA responsible for acetylcholine synthesis and secretion were increased and the phosphatidylcholine (PC) content were decreased in prefrontal cortex (PFC) of IBD mice compared to the Control. Fecal Metagenomics showed that the microbiome and lipid metabolism were also abnormal in IBD mice. Since both acetylcholine and PC are choline metabolites, we inferred that the IBD mice may suffer from choline deficiency and choline metabolism disorder. Following supplementation of CDP-choline, experimental subjects showed improvements through decreased anxiety-like behaviors, reduced PC degradation and increased acetylcholine synthesis in the PFC. In addition, CDP-choline treatment was shown to restore the gut microbiome and lipid metabolism disorders characteristic of DSS treatment. This study provides compelling evidence to suggest that choline metabolism plays a key role in the development and treatment of mood disorders in IBD patients, and choline and its metabolites may play a key role in maintaining the stability of the gut-brain axis.