Choline metabolism in regulating inflammatory bowel disease-linked anxiety disorders: A multi-omics exploration of the gut-brain axis

Abstract

Anxiety and depression caused by inflammatory bowel disease (IBD) negatively affect the mental health of patients. Emerging studies have demonstrated that the gut-brain axis (GBA) mediates IBD-induced mood disorders, but the underlying mechanisms of these findings remain unknown. Therefore, it's vital to conduct comprehensive research on the GBA in IBD. Multi-omics studies can provide an understanding of the pathological mechanisms of the GBA in the development of IBD, helping to uncover the mechanisms underlying the onset and progression of the disease. Thus, we analyzed the prefrontal cortex (PFC) of Dextran Sulfate Sodium Salt (DSS)-induced IBD mice using transcriptomics and metabolomics. We observed increased mRNA related to acetylcholine synthesis and secretion, along with decreased phosphatidylcholine (PC) levels in the PFC of DSS group compared to the control group. Fecal metagenomics also revealed abnormalities in the microbiome and lipid metabolism in the DSS group. Since both acetylcholine and PC are choline metabolites, we posited that the DSS group may experience choline deficiency and choline metabolism disorders. Subsequently, when we supplemented CDP-choline, IBD mice exhibited improvements, including decreased anxiety-like behaviors, reduced PC degradation, and increased acetylcholine synthesis in the PFC. In addition, administration of CDP-choline can restore imbalances in the gut microbiome and disruptions in lipid metabolism caused by DSS treatment. This study provides compelling evidence to suggest that choline metabolism plays a crucial role in the development and treatment of mood disorders in IBD. Choline and its metabolites appear to have a significant role in maintaining the stability of the GBA.

Keywords

• Inflammatory bowel disease
• Gut-brain axis
• Anxiety-like behaviors
• Choline
• Choline metabolism