Toward a Deeper Understanding of Gut Microbiome in Depression: The Promise of Clinical Applicability

Abstract

The emergence of the coronavirus disease 2019 pandemic has dramatically increased the global prevalence of depression. Unfortunately, antidepressant drugs benefit only a small minority of patients. Thus, there is an urgent need to develop new interventions. Accumulating evidence supports a causal relationship between gut microbiota dysbiosis and depression. To advance microbiota‐based diagnostics and therapeutics of depression, a comprehensive overview of microbial alterations in depression is presented to identify effector microbial biomarkers. This procedure generated 215 bacterial taxa from humans and 312 from animal models. Compared to controls, depression shows significant differences in β‐diversity, but no changes in microbial richness and diversity. Additionally, species‐specific microbial changes are identified like increased Eggerthella in humans and decreased Acetatifactor in rodent models. Moreover, a disrupted microbiome balance and functional changes, characterized by an enrichment of pro‐inflammatory bacteria (e.g., Desulfovibrio and Escherichia/Shigella) and depletion of anti‐inflammatory butyrate‐producing bacteria (e.g., Bifidobacterium and Faecalibacterium) are consistently shared across species. Confounding effects of geographical region, depression type, and intestinal segments are also investigated. Ultimately, a total of 178 species and subspecies probiotics are identified to alleviate the depressive phenotypes. Current findings provide a foundation for developing microbiota‐based diagnostics and therapeutics and advancing microbiota‐oriented precision medicine for depression.

Gut microbiota and its metabolites in depression: from pathogenesis to treatment

“…1 ) by reporting changes in the gut microbial composition of MDD patients compared to healthy individuals, particularly in terms of microbial diversity and the relative abundance of specific bacterial taxa. 3 , 12 , 13 Although the findings between studies have been inconsistent, enriched pro-inflammatory bacteria and depletion of anti-inflammatory bacteria have been the most consistent findings 3 , 13 ; this is similar to other disease conditions which are linked with systemic and gut inflammation, further strengthening the case for the inflammatory hypothesis of depression. In depression, Firmicutes, Actinobacteria, and Bacteroidetes are the most affected phyla 2 , 14 ; especially an increase in the Bacteroidetes/Firmicutes ratio in MDD patients, characterized by an enrichment of the genus Bacteroides and a depletion of the genera Blautia , Faecalibacterium, and Coprococcus.…”

“…In depression, Firmicutes, Actinobacteria, and Bacteroidetes are the most affected phyla 2 , 14 ; especially an increase in the Bacteroidetes/Firmicutes ratio in MDD patients, characterized by an enrichment of the genus Bacteroides and a depletion of the genera Blautia , Faecalibacterium, and Coprococcus. 3 , 12 , 13 , 15 An increase in Eggerthella and decrease in Sutterella were also consistently demonstrated in patients with MDD. 3 , 12 , 13 , 16 Driven by succession and within-host evolution throughout life, gut microbiota have become increasingly pathogenic, 17 , 18 leading to possible distinct microbial characteristics in MDD patients of different ages.…”

“… 3 , 12 , 13 , 15 An increase in Eggerthella and decrease in Sutterella were also consistently demonstrated in patients with MDD. 3 , 12 , 13 , 16 Driven by succession and within-host evolution throughout life, gut microbiota have become increasingly pathogenic, 17 , 18 leading to possible distinct microbial characteristics in MDD patients of different ages. 19 There are also regional differences in microbial compositions in patients with MDD.…”

“…For example, several taxa were primarily identified in patients from China, such as increased Eggerthella and decreased Coprococcus, and Fusicatenibacter . 3 However, simple association studies do not provide information about causality. Transplanting of fecal microbiota from MDD patients to induce depressive-like behaviors in rodents suggests that microbial dysbiosis precedes MDD onset and might play a causal role in MDD.…”

“…MDD is associated with microbial dysbiosis, which is defined as an alteration in microbial diversity owing to the disrupted balance of microbiota and corresponding functional changes. 3 Circumstantial evidence comes from an observed increased risk of severe mental disorders (e.g., depression, anxiety, and psychosis) following antibiotic use, even 5–10 years after use. 4 , 5 , 6 A recent systematic review indicated the association between antibiotics use and subsequent development of depression.…”