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The severity of depression is associated with the diversity of the gut microbiota.

Severity of the major depressive disorder is closely linked to microbial diversity in the gut.

Participants with moderate and severe depression showed a significant increase in the abundance of Bacteroides species, while Ruminococcus and Eubacterium were predominantly depleted in participants with severe depression.

Depression, also known as the major depressive disorder, is the most common type of mental illness, affecting over 350 million people worldwide. The main symptoms of depression include persistent feelings of sadness, loss of interest or pleasure in activities, changes in appetite or weight, sleep disturbances, fatigue, feelings of worthlessness or guilt, difficulty concentrating or making decisions, and recurrent thoughts of death or suicide. As a result, it imposes a substantial social burden on both the individuals affected by it and society as a whole.

The microbiota-gut-brain axis, a complex network enabling communication between the diverse community of microorganisms residing in the gastrointestinal tract and the brain, has been discovered through novel studies. As this communication occurs in both directions, researchers have been investigating the connections between the composition of the gut microbiota and psychological aspects such as cognition, well-being, and mental health.

To delve into the differences in gut microbiota composition among individuals experiencing depression but with varying symptom levels, the study was conducted by Xi Hu and colleagues. Recognizing the limitations of previous methods used to identify bacterial species with accuracy, they opted to employ metagenome sequencing for this purpose.

Metagenome sequencing is a genomic technique utilized to analyze the genetic material, DNA or RNA, existing in a complex mixture of microorganisms, such as those present in environmental samples or within the human body. Rather than focusing on the genetic material of a single organism, metagenome sequencing enables the simultaneous analysis of the collective genetic material of an entire microbial community. In this case, the procedure was employed to evaluate the microbial composition of participants’ guts and was conducted on stool samples.

A total of 138 individuals with varying levels of depression severity, ranging from mild to severe, were included as study participants, along with 155 healthy individuals serving as controls. The severity of depression was assessed using the HAMD-17 scale. Participants who were pregnant or breastfeeding, had used antibiotics within one month prior to sampling, had a history of alcohol or substance abuse, chronic somatic diseases, or other severe psychiatric disorders were excluded from the study.

Stool samples were collected at the clinical center where the study was conducted, specifically in the morning between 7 am and 10 am. The samples were stored in sterile tubes at 4 °C and then transferred to a −80 °C refrigerator. Processing of the samples was completed within 6 hours.

The results revealed that, at the family level, Bacteroidaceae, Lachnospiraceae, Ruminococcaceae, and Prevotellaceae were the major high abundance bacterial taxa in both healthy participants and those with depression. At the genus level, Bacteroides, Faecalibacterium, Blautia, and Prevotellaceae were the major high abundance bacterial taxa in both groups.

Compared to the healthy control group, an increase in the abundance of bacteria from the Bacteroides group was observed in participants with moderate and severe depression. In the moderate depression symptom group, Faecalibacterium and Escherichia were decreased, while Ruminococcus and Eubacterium were decreased only in the severe depression symptoms group.

When examining enterotypes, distinct types of bacterial communities within the human gut microbiota, it was found that an enterotype dominated by Faecalibacterium was more abundant in the healthy group, while two enterotypes dominated by Bacteroides were more abundant in the group of patients with depression.

“The enrichment of Bacteroidetes and depletion of Ruminococcus and Eubacterium were observed in the gut microbiota of patients with moderate and severe major depressive disorder. Moreover, the major enterotype in healthy controls was Faecalibacterium. Furthermore, we identified a microbial marker panel capable of distinguishing major depressive disorder patients with different severity,” concluded the researchers.

The study contributes significantly to the scientific understanding of the connections between gut microbiota composition and mental health. However, it should be noted that the study design does not allow for any cause-and-effect conclusions to be drawn. Additionally, all samples were collected from the same regional clinical center, so results on individuals from other regions or countries may vary.


Disturbed gut microbiota is a potential factor in the pathogenesis of major depressive disorder (MDD), yet whether gut microbiota dysbiosis is associated with the severity of MDD remains unclear. Here, we performed shotgun metagenomic profiling of cross-sectional stool samples from MDD (n = 138) and healthy controls (n = 155). The patients with MDD were divided into three groups according to Hamilton Depression Rating Scale 17 (HAMD-17), including mild (n = 24), moderate (n = 72) and severe (n = 42) individuals, respectively. We found that microbial diversity was closely related to the severity of MDD. Compared to HCs, the abundance of Bacteroides was significantly increased in both moderate and severe MDD, while Ruminococcus and Eubacterium depleted mainly in severe group. In addition, we identified 99 bacteria species specific to severity of depression. Furthermore, a panel of microbiota marker comprising of 37 bacteria species enabled to effectively distinguish MDD patients with different severity. Together, we identified different perturbation patterns of gut microbiota in mild-to-severe depression, and identified potential diagnostic and therapeutic targets.

Changes of gut microbiota reflect the severity of major depressive disorder: a cross sectional study