Depression and anxiety in patients with active ulcerative colitis: crosstalk of gut microbiota, metabolomics and proteomics

Gut Microbes. 2021 Jan-Dec;13(1):1987779. doi: 10.1080/19490976.2021.1987779.

Abstract

Patients with ulcerative colitis (UC) have a high prevalence of mental disorders, such as depression and anxiety. Gut microbiota imbalance and disturbed metabolism have been suggested to play an important role in either UC or mental disorders. However, little is known about their detailed multi-omics characteristics in patients with UC and depression/anxiety. In this prospective observational study, 240 Chinese patients were enrolled, including 129 patients with active UC (69 in Phase 1 and 60 in Phase 2; divided into depression/non-depression or anxiety/non-anxiety groups), 49 patients with depression and anxiety (non-UC), and 62 healthy people. The gut microbiota of all subjects was analyzed using 16S rRNA sequencing. The serum metabolome and proteome of patients with UC in Phase 2 were analyzed using liquid chromatography/mass spectrometry. Associations between multi-omics were evaluated by correlation analysis. The prophylactic effect of candidate metabolites on the depressive-like behavior of mice with colitis was investigated. In total, 58% of patients with active UC had depression, while 50% had anxiety. Compared to patients with UC without depression/anxiety, patients with UC and depression/anxiety had lower fecal microbial community richness and diversity, with more Lactobacillales, Sellimonas, Streptococcus, and Enterococcus but less Prevotella_9 and Lachnospira. Most metabolites (e.g., glycochenodeoxycholate) were increased in the serum, while few metabolites, including 2'-deoxy-D-ribose and L-pipecolic acid, were decreased, accompanied by a general reduction in immunoglobulin proteins. These related bacteria, metabolites, and proteins were highly connected. A prophylactic administration of 2'-deoxy-D-ribose and L-pipecolic acid significantly reduced the depressive-like behaviors in mice with colitis and alleviated the inflammatory cytokine levels in their colon, blood and brain. This study has identified a comprehensive multi-omics network related to depression and anxiety in active UC. It is composed of a certain set of gut microbiota, metabolites, and proteins, which are potential targets for clinical intervention for patients with UC and depression/anxiety.

Keywords: Ulcerative colitis; microbiota-gut-brain axis; multi-omics analyses.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Animals
  • Anxiety / blood
  • Anxiety / complications
  • Anxiety / microbiology*
  • Bacteria / classification
  • Bacteria / genetics
  • Bacteria / isolation & purification
  • Bacteria / metabolism
  • Brain-Gut Axis*
  • Colitis, Ulcerative / blood
  • Colitis, Ulcerative / complications
  • Colitis, Ulcerative / microbiology*
  • Depression / blood
  • Depression / complications
  • Depression / microbiology*
  • Feces / microbiology
  • Gastrointestinal Microbiome*
  • Humans
  • Metabolomics
  • Mice
  • Middle Aged
  • Prospective Studies
  • Proteomics
  • Young Adult

Grants and funding

This study was supported by the National Natural Science Foundation of China [grant numbers 82174379, 82001206], the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD) [grant number ZYX03KF018], the Jiangsu Province “333 High-Level Talent Training Project”- second level [grant number BRA2017536], and the Postgraduate Research & Practice Innovation Program of Jiangsu Province [grant number KYCX21_1639].