Search results

We searched for 7,055 articles in PubMed (2,303), Embase (4,062), and PsycINFO (690). 24 articles were finally included in the systematic review for further analysis (Fig. 2).

Fig. 2

PRISMA flow diagram of study selection

Study characteristics

The characteristics of the 24 studies included were shown in Table 1. There were 20 studies from China, and 4 studies from Norway [14], Ireland [15], USA [16] and Spain [17], respectively. We collected the proportion of female, age, study samples and diagnostic criteria. Among them, 19 studies were patients with depression (MDD: n = 16; No specific type: n = 3) [14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33], 3 studies were patients with GAD(Generalized anxiety disorder) [34–35, 36], and 2 studies included patients with depression and anxiety.(MDD&GAD: n = 1; No specific type: n = 1) [16, 37]. Diagnostic criteria: Sixteen studies used DSM-IV criteria for diagnosis, five used ICD-10, one used CCDCMD-3, one used HDRS-17 for diagnosis and assessment, and one study did not report the diagnostic criteria [15]. In addition, we have extracted the sequencing method of intestinal microflora. Twenty-one studies used 16s rRNA gene sequencing from different regions, and four studies used Shotgun metagenomics sequencing [22, 24, 26, 29].

Table 1 Characteristics of included studiesQuality assessment

In Table 2, the quality assessment of the studies showed that most of the studies were of high quality, with 22 studies scoring 7 or more stars. Two [15, 17] studies were of low quality (6 points). All studies were scored in “Definition of controls”, “Comparability of cases and controls”, “Ascertainment of exposure” and “Same method of ascertainment for cases and controls”, but none of which was reported “Non-response rate”.

Table 2 Methodological quality of included studiesα-diversity and β-diversity

The difference of α-diversity and β-diversity index between the patients and the control group is shown in Table 3.

Table 3 Summary of bacterial diversity assessments of the included studiesα-diversity

α-diversity is used to reflect the diversity of microbial community. Five indicators were used to evaluate α diversity, including Chao, ACE, Shannon, Simpson, and phylogenetic diversity in the included studies. The most widely adopted index in depression is the Shannon index, which was examined in every study except two [14, 34].There was no significant difference in alpha diversity between patients with depression and healthy participants in 16 of 21 studies [14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30, 34, 37]. However, four studies showed that α-diversity was lower in the depression patients groups compared with control groups [15, 19, 29, 31]. One study found an increased Shannon index in depressive disorders [33].

In the studies by Mason et al. [16] and Jiang H et at [36], there was no significant difference in alpha diversity between the anxiety disorders and the control group. Three studies found lower alpha diversity in the GAD compared with control groups [34, 35, 37].

β-diversity

β-diversity is a measure of inter-individual diversity that examines similarity of communities compared with the other samples analysed. The distance between samples can be calculated by weighted (Bray-Curtis and Weighted Unifrac) and unweighted (Jaccard and Unweighted Unifrac) algorithms to obtain the β value between sample. The Beta diversity analysis is performed based on the distance matrix, such as PCA and PCoA. Moreover, combined with other multivariate statistical analysis methods (OPLS-DA, PLS-DA, PERMANOVA, ANOSIM) to detect the variability between samples.

Findings in depressive disorders

β-diversity between participants with depressive disorders and controls was reported in 20 studies, with a variety of measures. Only one study did not perform β-diversity. Seven studies found no difference between depression and controls. Four studies [17, 18, 29, 37] used metric methods based on Bray-Curtis. Two [16, 33] used weighted or unweighted UniFrac. 13 studies [14, 15, 20, 22,23,24,25,26,27,28, 30,31,32] found significant differences in participants with a depressive disorder relative to controls, and most studies used PCoA analysis (10 of 13) [15, 20, 22,23,24,25,26, 30,31,32].

Findings in anxiety disorders

Five studies comparing anxiety disorders with healthy controls, four studies analysed β-diversity. Three studies reported that there were differences between two groups [35,36,37], and one study found no significant difference [16].

Taxonomic findingsFindings in depressive disorders

We summarized the representative taxa findings of depression patients versus controls at three levels (phylum, family, and genus levels) (Fig. 3). The relative abundance of bacteria was found significant differences between the two groups involving in 4 phyla, 8 families and 21 genera. The tree gram was used to illustrate the relationships between the shown genera, families, and phyla. As shown in Fig. 4, there were four phyla including Bacteroidetes, Firmicutes, Actinobacteria and Proteobacteria. Bacteroidetes involved in 5 families and 4 genera. Firmicutes involved in 8 families and 12 genera. Actinobacteria involved in 3 families and 4 genera. Proteobacteria involved in 2 families and 1 genus.

Fig. 3

Summary of taxa abundance differences in depression patients compared to control groups. (A) phylum level; (B) family level; (C) genus level

Fig. 4

Tree gram of the gut microbiota in depressive disorders

At the phylum level, eleven studies showed significant differences of relative abundance. The differential gut microbiota mainly included Bacteroidetes, Firmicutes, Actinobacteria and Proteobacteria. The most consistent changes were the enrichment of Actinobacteria (4 of 5 studies) [18, 22, 28, 29]and Proteobacteria (3 of 4 studies) [29, 31, 33] in depression disorders. The results of the study reported that relative abundance differences in Bacteroidetes and Firmicutes were contradictory. A lower abundance of Bacteroidetes (4 of 9 studies) [22, 28, 29, 32] and Firmicutes (4 of 7 studies) in depression was observed.

At the family level, five gut microbiota showed consistent results, including Rikenellaceae (4 studies) [21, 24, 25, 33], Porphyromonadaceae (4 studies) [24, 25, 28, 33], Prevotellaceae (3 studies) [15,