Gut microbiota in patients with first-episode major depressive disorder: composition and correlations with gastrointestinal symptoms

Abstract:

[Background] Major depressive disorder (MDD) is a common major mental disorder and most MDD patients have gastrointestinal (GI) symptoms. However, little is known about the occurrence mechanisms of GI symptoms in MDD. [Objective] To explore the gut microbiota composition and its correlations with inflammation markers and GI symptoms in the patients with first-episode MDD, providing a theoretical basis for the treatment of MDD. [Methods] The participants included 91 first-episode, drug-naive MDD patients and 105 healthy controls (HCs). The 16S rRNA gene sequencing and bioinformatics tools were employed to reveal the composition of fecal microbiota. The levels of high-sensitivity C-reactive protein (hs-CRP), interleukin-1 beta (IL-1β), IL-6, IL-10, and tumor necrosis factor-alpha (TNF-α) in the peripheral blood were measured via enzyme-linked immunosorbent assay (ELISA). Gastrointestinal symptom rating scale (GSRS) and Hamilton depression scale (HAMD) were used to evaluate the severity of GI symptoms and depression symptoms, respectively. [Results] All the MDD patients were accompanied by GI symptoms, and the incidence of anorexia, early satiety, nausea, and vomiting was higher than 70%. Compared with HCs, MDD patients had elevated level of hs-CRP and showed different alpha diversity and beta diversity of gut microbiota (P＜0.05). Linear discriminant analysis effect size (LEfSe) showed that MDD patients had higher relative abundance of Geodermatophilus, Alloscardovia, Bifidobacterium, Blautia, Leptothrix, Rubrivivax, Massilia, Haemophilus, Candidatus Xiphinematobacter, and Chthoniobacter and lower relative abundance of Bacteroides, Parabacteroides, SMB53, Anaerostipes, Clostridium, Lachnospira, Roseburia, Faecalibacterium, Ruminococcus, Dialister, Phascolarctobacterium, and Sutterella. Furthermore, the correlation analysis revealed that the relative abundance of Roseburia, Sutterella, and Parabacteroides were negatively correlated with hs-CRP, total score of HAMD-17, and the total score and some item scores of GSRS (P＜0.05). [Conclusion] This study demonstrates that compared with HCs, MDD patients showed elevated hs-CRP. The altered gut microbiota is closely associated with hs-CRP and depression and GI symptoms in MDD patients.

Key words:major depressive disorder;gastrointestinal symptoms;gut microbiota;gut-brain axis;high-sensitivity C-reactive protein (hs-CRP)