Table 1 Characteristics of studies included in the meta-analysis.

From: Gut microbiota composition in depressive disorder: a systematic review, meta-analysis, and meta-regression

Study

Country

Definition of disorder

Scale score of patients

Sample size n

Mean age

% Female

Mean BMI

Smoking

Alcohol

Medicated

Sequencing

Diversity assessments

Aizawa et al. [23]

Japan

DSM-IV

HDRS

16.9(6.8)

P: 43

HC: 57

P: 39.4

HC: 42.3

P: 41.9

HC: 61.4

P:23.2

HC: 22.2

Nr

Nr

Yes

16S rRNA-targeted RT-qPCR

α: not measured

β: not measured

Bai et al. [24]

China

DSM-IV

HDRS

25.3 (6.0)

P: 60

HC: 60

P: 35.6

HC: 35.1

P: 65.0

HC: 60.0

P: 20.9

HC: 21.2

Nr

No

No

16S rRNA

Nr

α: Chao1., Shannon, Simpson, PD

β: measured, not reported

Caso et al. [25]

Spain

DSM-IV-TR

HDRS

21.17

P: 46

HC: 45

P: 42.1

HC: 44.7

P: 78.3

HC: 75.5

<30

Yes

Yes

Yes

16S rRNA

V3-V4

α: Shannon

β: Jaccard,Bray-Curtis

Chahwan et al. [26]

Australia

M.I.N.I

BDI

28.4(9.9)

P: 71

HC: 20

P: 36.0

HC:36.0

P: 69.0

HC: 75.0

Nr

Yes

Yes

Yes

16S rRNA

V3-V4

α: Observed sp., Chao1, Shannon

β: UniFrac (weighted)

Chen et al. [28]

China

DSM-IV

HDRS

25.6(4.7)

P: 10

HC: 10

P: 43.9

HC:39.6

P: 50.0

HC: 50.0

P: 23.5

HC: 22.6

No

No

Yes

Metaproteomics

α: not measured

β: not measured

Chen et al. [27]

China

DSM-5

HDRS

28.0(4.6)

P: 62

HC: 46

P: 39.6

HC: 36.9

P: 100.0

HC: 100.0

P: 22.0

HC: 22.2

No

No

No

16S rRNA

V3-V4

Shotgun Metagenomics

α: Observed sp., Chao1, ACE, Shannon, Simpson

β: UniFrac (weighted & unweighted)

Chen et al. [88]

Taiwan

DSM-5

BDI

16.6 (14.6)

P: 10

HC: 10

P: 40.9

HC: 38.2

P: 80.0

HC: 70.0

P: 20.8

HC: 22.0

Nr

Nr

Yes

16S rRNA

V4 and V3-V4

α: Richness, Shannon

β: Bray-Curtis

Chung et al. [29]

Taiwan

DSM-5

BDI

19.2 (12.5)

P: 36

HC: 37

P: 45.8

HC: 41.2

P: 82.4

HC: 62.2

P: 22.8

HC: 24.0

Yes

Nr

Yes

16S rRNA

V3-V4

α: Observed sp., Chao1, Shannon, PD

β: UniFrac (weighted & unweighted)

Dong et al. [30]

China

DSM-5

HDRS

29.3(7.5)

P: 23

HC: 10

P:30.0

HC: 30.2

P: 69.6

HC: 60.0

P: 21.9

HC:21.5

Nr

No

No

16S rRNA

V3-V4

α: ACE, Chao1, Simpson, Shannon

β: Bray-Curtis

Dong et al. [89]

China

DSM-IV

HDRS

28.3 (7.6)

P: 63

HC: 30

P: 28.3

HC: 29.2

P: 68.3

HC:66.7

P: 21.7

HC: 21.5

Yes

Yes

No

16S rRNA

Nr

α: Chao1, Simpson, Shannon

β: Bray-Curtis

Fontana et al. [31]

Italy

DSM-IV-TR

Nr

P: 34

HC: 20

P: 53.3

HC: 42.4

P: 70.6

HC: 35.0

P: 24.5

HC: 22.6

Yes

Yes

Yes

16S rRNA

V3-V4

α: not measured

β: not measured

Han et al. [90]

China

DSM-IV

HDRS

Nr

P: 51

HC: 30

P: 27.1

HC: 29.2

P: 72.5

HC: 66.7

P: 21.6

HC: 21.5

Nr

Nr

No

16S rRNA

V3-V4

α: Chao, ACE, Shannon, Simpson

β: Bray–Curtis

Huang et al. [32]

China

ICD-10

Nr

P: 27

HC: 27

P: 48.7

HC: 42.3

P: 74.1

HC: 74.1

P: 23.8

HC: 23.4

Nr

Nr

No

16S rRNA

V3-V4

α: Chao1, ACE, Shannon, PD

β: UniFrac (weighted & unweighted)

Jiang et al. [33]

China

DSM-IV

HDRS

29.8 (7.6)

P: 29

HC: 30

P: 25.3

HC: 26.8

P: 37.9

HC: 50.0

P: 20.3

HC: 19.6

Yes

Nr

Yes

16S rRNA

V1-V3

α: Chao1, ACE, Shannon, Simpson, Evenness

β: UniFrac (unweighted)

Kelly et al. [22]

Ireland

DSM-IV

HDRS

19.5 (14.0)

P: 34

HC: 33

P: 45.8

HC: 45.8

P: 32.8

HC: 42.4

P: 26.2

HC: 24.6

Yes

Yes

Yes

16S rRNA

Nr

α: Observed sp., Chao1, Shannon, PD

β: UniFrac (weighted & unweighted),

Bray-Curtis

Kim et al. [91]

Korea

CES-D

Nr

P:167

HC:1071

P: 44.0

HC:45.7

P: 55.1

HC:33.2

P: 23.1

HC:23.8

Nr

Nr

Nr

16S rRNA

V3-V4

α: Observed ASVs., Pielou’s evenness, Shannon,PD

β: Bray-Curtis, Jaccard, UniFrac (weighted & unweighted)

Kovtun et al. [92]

Russia

ICD-10

HDRS

21.3(3.6)

P: 36

HC:38

P: 30.9

HC:34.0

P: 47.2

HC:50.0

P: 22.4

HC:24.4

Nr

Nr

No

Metagenomics

α: Shannon

β: not measured

Lai et al. [34]

China

DSM-5

HDRS

19.8 (3.0)

P: 26

HC: 29

P: 43.7

HC: 39.4

P: 69.2

HC: 55.2

P: 21.2

HC: 21.1

Nr

Nr

Yes

Shotgun

Metagenomics

α: Shannon, Fisher

β: Bray–Curtis

Li et al. [93]

China

ICD-10

HDRS

Nr

P: 40

HC: 22

P: 37.9

HC: 44.0

P: 62.5

HC:40.9

Nr

Yes

Yes

No

16S rRNA

V3-V4

α: Chao, ACE, Shannon, Simpson

β: not measured

Lin et al. [35]

China

DSM-IV-TR

HDRS

Nr

P: 10

HC: 10

P: 36.2

HC: 38.1

P: 40.0

HC: 40.0

P: 23.8

HC: 24.2

Yes

Nr

Yes

16S rRNA

V3-V4

α: not measured

β: UniFrac (weighted)

Liu et al. [38]

China

DSM-IV

SDS

Nr

P: 15

HC: 20

P: 44.8

HC: 43.9

P: 73.3

HC: 65.0

P: 22.0

HC: 24.6

Nr

Nr

No

16S rRNA

V1-V3

α: Shannon

β: not measured

Liu et al. [37]

USA

DSM-5

PROMIS

P:25.0 (6.9)

P: 43

HC: 47

P: 21.9

HC: 22.1

P: 88.4

HC: 72.3

Nr

No

Nr

Yes

16S rRNA

V4

α: Observed sp., Shannon, PD

β: UniFrac (weighted & unweighted), Bray-Curtis

Liu et al. [36]

China

DSM-IV

HDRS

P:20.1(4.2)

P: 66

HC: 43

P: 24.2

HC: 23.7

P: 59.1

HC: 53.5

P: 21.5

HC: 21.8

Nr

Nr

No

16S rRNA

V3-V4

α:Shannon, Simpson, Observed sp., Chao1, PD, Pielou’s evenness

β:Jaccard

Mason et al. [39]

USA

DSM-IV

QIDS-SR

15.6 (3.2)

P: 14

HC: 10

P: 41.9

HC: 33.0

P:78.6

HC:60.0

P: 31.0

HC: 25.6

Nr

No

Yes

16S rRNA

V4

α: not measured

β: UniFrac (weighted)

Naseribafrouei et al. [40]

Norway

ICD-10

MADRS

26.3 (7.6)

P: 37

HC: 18

P: 49.2

HC: 46.1

P:54.1

HC:61.1

P: 25.9

HC: 24.7

Nr

Nr

Nr

16S rRNA

Nr

α: Observed sp., Simpsons

β: not measured

Rong et al. [41]

China

DSM-5

HDRS

20.2 (3.1)

P: 31

HC: 30

P: 41.6

HC: 39.5

P: 71.0

HC:53.3

P: 21.5

HC: 22.0

Nr

Nr

Yes

Shotgun

Metagenomics

α: Chao 1, Shannon, Inv. Simpson, Gm coefficient

β: Bray-Curtis

Shen et al. [42]

China

M.I.N.I

HDRS

Nr

P: 30

HC: 30

P: 44.8

HC: 44.0

P: 56.7

HC:50.0

P: 24.0

HC: 23.8

Yes

Yes

No

16S rRNA

V3-V4

α:Ace, Chao1, Shannon, Simpson

β:Jaccard

Stevens et al. [44]

USA

DSM-IV

Nr

P: 20

HC: 20

P: 34.0

HC: 34.0

P: 50.0

HC: 70.0

Nr

Nr

Nr

Yes

16S rRNA

V3-V4

α: not measured

β: Bray-Curtis

Stevens et al. [43]

USA

DSM-5

Nr

P: 7

HC: 21

P: 63.8

HC: 53.0

P: 57.1

HC: 61.9

P: 27.3

HC: 30.7

Nr

Nr

Nr

Shotgun

Metagenomics

α: not measured

β: not measured

Sun et al. [94]

China

DSM-IV

HDRS

20.6(3.2)

P:31

HC: 29

P: 25.3

HC:24.8

P: 48.4

HC:55.2

P: 22.4

HC:22.0

Nr

No

No

16S rRNA

V3-V4

α: Observed sp., Chao1, Simpson, Shannon, PD, Pielou’s evenness

β: not measured

Thapa et al. [45]

USA

DSM-IV-TR

BDI

Nr

P: 110

HC: 27

P: 19.5

HC: 20.3

P: 65.5

HC: 37.0

Nr

Nr

Yes

Yes

16S rRNA

V4

α:Observed sp., Chao1, ACE, Shannon, PD

β:UniFrac (weighted & unweighted),

Bray-Curtis, Aitchison

Tsai et al. [95]

Taiwan

DSM-IV-TR

HDRS

13.6(7.3)

P: 36

HC: 17

P: 65.6

HC: 64.1

P: 77.8

HC: 52.9

P: 23.4

HC: 24.5

Nr

Nr

Nr

16S rRNA

V3-V4

α: Shannon, PD

β:UniFrac (unweighted)

Valles-Colomer et al. [46]

Belgium

GP-reported depression

Nr

P: 80

HC: 70

P: 50.9

P: 54.6

P: 24.9

Nr

Nr

Yes

16S rRNA

V4

α: not measured

β: not measured

Yang et al. [47]

China

DSM-IV

HDRS

22.2

P: 156

HC: 155

P: 29.6

HC: 29.1

P: 64.1

HC: 58.7

P: 22.3

HC: 22.4

Nr

Nr

Yes

Shotgun

Metagenomics

α: Chao1, Shannon, Inv. Simpson

β: Bray-Curtis

Ye et al. [48]

China

DSM-IV

HDRS

27.9(2.8)

P: 26

HC: 28

P: 26.0

HC: 26.0

P: 80.8

HC: 75.0

P: 19.8

HC: 21.6

Nr

Nr

No

16S rRNA

V3-V4

α: Chao1, Shannon

β: UniFrac (unweighted)

Yuan et al. [49]

China

PHQ-9

12.5(5.4)

P: 49

HC: 62

P: 36.9

HC: 41.6

P: 59.2

HC: 58.1

P: 22.1

HC: 23.3

Yes

Yes

Nr

16S rRNA

V3-V4

α: Shannon, PD

β: not measured

Zhang et al. [50]

China

ICD-10

HDRS

14.1(3.0)

P: 36

HC: 45

P: 36.8

HC: 39.3

P: 41.7

HC: 57.8

P: 24.5

HC: 23.9

Yes

Nr

No

16S rRNA

V4-V5

α: Chao, ACE, Shannon, Simpson

β: UniFrac (weighted & unweighted), Bray-Curtis, Jaccard

Zhang et al. [96]

China

HDRS

19.5(0.8)

P: 40

HC: 30

P: 40.9

HC: 44.2

P: 73.7

HC: 69.6

Nr

Nr

Nr

No

16S rRNA

V4

α:Chao, ACE, Observed sp.

β: Bray-Curtis

Zhao et al. [51]

China

DSM-5

HDRS

24.8(3.1)

P: 24

HC: 26

P: 30.0

HC: 31.3

P: 70.8

HC: 69.2

Nr

Nr

No

No

Nr

α: not measured

β: not measured

Zheng et al. [19]

China

DSM-IV-TR

HDRS

P: 22.8(4.4)

P: 58

HC: 63

P: 40.6

HC: 41.8

P: 62.1

HC: 63.5

P: 22.0

HC: 22.6

Yes

Nr

Yes

16S rRNA

V3-V5

α: Observed sp., Shannon, Simpson, PD

β: UniFrac (weighted & unweighted)

Zheng et al. [52]

China

DSM-IV

HDRS

22.9

P: 165

HC: 217

P: 29.3

HC: 30.8

P: 64.2

HC: 56.2

P: 22.3

HC: 22.5

Nr

Nr

Yes

16S rRNA

V3-V4

α:Chao, ACE, Shannon, Inv. Simpson

β:PLS-DA

Zheng et al. [53]

China

ICD-10

HDRS

20.2(7.9)

P: 30

HC: 30

P: 30.8

HC: 33.4

P: 60.0

HC: 56.7

P: 21.5

HC: 22.9

Nr

Nr

No

16S rRNA

Nr

α: Chao1, ACE, Shannon, Simpson, Sobe

β: not measured

Zhou et al. [54]

China

DSM-IV

HDRS

13.5(3.5)

P: 39

HC: 18

P: 33.6

HC: 32.6

P: 100.0

HC: 100.0

P: 21.5

HC: 20.9

Nr

Nr

No

16S rRNA

V4

α:Observed sp., Shannon, PD, Evenness

β:UniFrac (weighted)

Zhou et al. [97]

China

ICD-10

SDS

76.3(8.5)

P: 70

HC: 101

P: 13.7

HC: 13.5

P: 62.2

HC: 53.4

P: 19.6

HC: 19.9

Yes

No

Yes

16S rRNA

V3-V4

α:Chao1, ACE, Shannon, Sobs

β:UniFrac (weighted)

  1. BMI body mass index, P patient, HC healthy control, ICD International Classification of Diseases, DSM Diagnostic and Statistical Manual of Mental Disorders, MINI Mini-International Neuropsychiatric Interview, GP general practitioner, CES-D Center for Epidemiologic Studies Rating Scale for Depression, ACE abundance-based coverage estimator. RT-qPCR real time quantitative polymerase chain reaction, PD phylogenetic diversity, PLS-DA partial least squares discriminant analysis, OPLS-DA orthogonal projections to latent structures discriminant analysis, n number, Nr not reported, HDRS Hamilton Depression Rating Scale, PHQ-9 Patient Health Questionnaire-9.