alleviates dextran sodium sulfate-induced colitis and depression-like behaviour by facilitating gut-brain axis balance.

Background: Patients with inflammatory bowel disease (IBD) have a higher prevalence of depression. Gut microbiota dysbiosis plays an important role in IBD and depression. However, few studies have explored the characteristic microbiota of patients with IBD and depression (IBDD), or their role in IBDD.

Methods: We performed deep metagenomic sequencing and 16S rDNA quantitative PCR to characterise the gut microbial communities of patients with IBDD and patients with IBD without depression (IBDND). We then assessed the effect of the microbiota on colitis and depression in mouse models of dextran sulfate sodium salt (DSS)-induced colitis and lipopolysaccharide (LPS)-induced depression. Furthermore, liquid chromatography-tandem mass spectrometry was used to analyse the microbiota-derived metabolites involved in gut-brain communication. Evans Blue tracer dye was used to assess blood-brain barrier (BBB) permeability.

Results: Our results showed that the faecal abundance of () was lower in patients with IBDD than in those with IBDND. In the DSS-induced colitis mouse model, the group showed a significantly lower disease activity index score, lesser weight loss, and longer colon length than the DSS group. Moreover, relieved depression-like behaviour in the DSS-induced colitis mouse model and in the LPS-induced depression mouse model. Furthermore, the key metabolite of was p-hydroxyphenylacetic acid (4-HPAA), which was found to relieve intestinal inflammation and alleviate depression-like behaviours in mouse models. By increasing the expression of the tight junction protein claudin-5 in the vascular endothelium of the BBB, and 4-HPAA play critical roles in gut-brain communication.

Conclusion: and -derived 4-HPAA ameliorated intestinal inflammation and relieved depressive symptoms through the gut-brain axis. Thus, administration of or 4-HPAA supplementation is a promising therapeutic strategy for treating IBD, particularly IBDD.