Crosstalk of multi-omics reveals specific characteristics in active ulcerative colitis patients with depression and anxiety

Abstract Background:Ulcerative colitis (UC) patients have a high incidence of mental disorders. The microbiota-gut-brain axis dysfunction is considered as one important pathogenesis of mental diseases. At present, little is known about how gut microbiota interact with the host in UC patients with depression and anxiety.Results: This prospective observational study enrolled 240 Chinese patients in two cohorts: the discovery cohort, including 69 active UC patients, 49 non-inflammatory bowel disease (IBD) depression and anxiety patients, and 62 healthy people, and the replication cohort of 60 active UC patients. About half of active UC patients showed symptoms of depression or anxiety. Through 16s rRNA sequencing, it was found that these UC patients accompanied with depression and anxiety had lower fecal microbial abundance with more Sellimonas , Eubacterium ventriosum group , Enterococcus , and Peptoclostridium , but less Prevotella_9 , Erysipelotrichaceae UCG_003 , Collinsella , and Dorea , compared with non-depressed/ anxious UC patients. Serum metabolome and proteome analysed using liquid chromatography/ mass spectrometry showed significantly increased glycochenodeoxycholate, stearoyllysophosphatidylcholine, and glyceryl stearates, while decreased 2'-deoxy-D-ribose and a set of immunoglobulin protein in the serum of UC patients with depression and anxiety. Through integration of multiple statistical analyses and multi-omics correlation analyses, we revealed a highly connected and comprehensive network, centring on Prevotella_9 and 1-stearoyl-sn-glycerol, composed of these bacteria, metabolites and proteins associated with UC-specific depression and anxiety.Conclusion: This study has identified a highly connected multi-omics network, composed of a set of gut microbiota, serum metabolites and proteins, specifically related to depression and anxiety in active UC. This network might influence host's mental state through mediating the effect of gut inflammation on synapse pruning in the central nervous system.