Table 1.
General Characteristics of included studies
| First author, year | Country | Ethnicity | Disease | Sample size (case) | Sample size (control) | Age (years) | Sample | Sequencing Method | Definition of obesity | Definition of metabolic diseases |
|---|---|---|---|---|---|---|---|---|---|---|
| Andoh, 2016 [18] | Japan | Asian | OB | 10 | 10 | 31–58 | Stool | 16s rRNA (V3–V4) | BMI ≥ 35.7 kg/m2 | NA |
| Bai, 2019 [19] | USA | Caucasian | OB | 43 | 224 | 7–18 | Stool | 16s rRNA (V4) | BMI > 95th percentile | NA |
| Chen, 2020 [20] | China | Asian | OB | 28 | 23 | 6–11 | Stool | 16s rRNA (V4) | Body mass index cut-offs for overweight and obesity in Chinese children and adolescents aged 2–18 years* | NA |
| Da Silva, 2020 [21] | Trinidad | Asian/Black | OB | 21 | 30 | 6–14 | Stool | 16s rRNA (not specified) | > 97th percentile | NA |
| Gao, 2018 [22] | China | Asian | OB | 167(OB: n = 145;OW: n = 22) | 25 | NW:25.4 ± 3.2; OW:30.1 ± 11.2; OB:29.2 ± 11.4 | Stool | 16s rRNA (V4) | NA | NA |
| Gao, 2018 [23] | China | Asian | OB | 39 | 38 | OB: 6.8 ± 1.6; NW: 6.0 ± 2.7 | Stool | 16S rRNA (V3–V4) | BMI ≥ 30 kg/m2 | NA |
| Haro, 2016 [24] | Spain | Caucasian | OB | 49 | 26 | Men: 61.15 ± 1.27; Women: 60.31 ± 1.40 | Stool | 16s rRNA (V4) | BMI ≥ 30 kg/m2 | NA |
| Houttu, 2018 [25] | Finland | Caucasian | OB | 47 | 52 | 30 ± 5 | Stool | 16s rRNA (not specified) | BMI ≥ 30 kg/m2 | NA |
| Hu, 2015 [26] | Korea | Asian | OB | 67 | 67 | 13–16 | Stool | 16s rRNA (V1–V3) | BMI ≥30 kg/m2 or ≥ 99th BMI percentile | NA |
| Kaplan, 2019 [27] | USA | Caucasian | OB | 294 | 293 | 18–74 | Stool | 16s rRNA (V4) | BMI ≥ 30 kg/m2 | NA |
| Liu, 2017 [28] | China | Asian | OB | 72 | 79 | OB:23.6 ± 3.7; NW:23.2 ± 1.8 | Stool | Metagenomics/16S rRNA (V3–V4) | BMI ≥ 30 kg/m2 | NA |
| Lopez-Contreras, 2018 [29] | Mexico | Hispanic/Latino | OB | 71 | 67 | 6–12 | Stool | 16s rRNA (V4) | BMI ≥ 95th percentile | NA |
| Lv, 2019 [30] | China | Asian | OB | 9 | 19 | 18–27 | Stool | 16S rRNA (V3–V4) | OW, BMI ≥ 24 kg/m2 OB, BMI ≥ 28 kg/m2 | NA |
| Mendez-Salazar, 2018 [31] | Mexico | Hispanic/Latino | OB | 12 | 12 | 9–11 | Stool | 16s rRNA (V3–V4) | BMI z-score≥ +2 standard deviations | NA |
| Nardelli, 2020 [32] | Italy | Caucasian | OB | 19 | 16 | 20–80 | Duodenal biopsies | 16s rRNA V4–V6 | BMI ≥ 30 kg/m2 | NA |
| Blasco, 2017 [33] | Spain | Caucasian | OB | 14 | 13 | 30–65 | Stool | Metagenomics | BMI ≥ 30 kg/m2 | NA |
| Davis, 2017 [34] | UK | Caucasian | OB | 54 (OB/OW:n = 27) | 27 | 19–70 | Stool | Metagenomics/16s rRNA (V4) | NA | NA |
| Dominianni, 2015 [35] | USA | Caucasian | OB | 11 | 82 | 30–83 | Stool | 16S rRNA (V3–V4) | BMI ≥ 25 kg/m2 | NA |
| Escobar, 2015 [36] | Colombia | Hispanic/Latino | OB | NA | 30 | 21–60 | Stool | 16s rRNA (V1–V3) | BMI ≥ 30.0 kg/m2 | NA |
| Kasai, 2015 [37] | Japan | Asian | OB | 33 | 23 | Non-obese:45.6 ± 9.6; Obese:54.4 ± 8.2 | Stool | 16s rRNA (V3–V4) | BMI ≥ 25kg/m2 | NA |
| Nirmalkar, 2018 [38] | Mexico | Hispanic/Latino | OB | 96 | 76 | 6–18 | Stool | 16s rRNA V3 | BMI ≥ 95th percentile | NA |
| Ottosson, 2018 [39] | Sweden | Caucasian | OB | NA | NA | > 18 | Stool | 16s rRNA (V1–V3) | BMI > 30.0 kg/m2 | NA |
| Peters, 2018 [40] | USA | Caucasian | OB | 388 | 211 | 18–86 | Stool | 16s rRNA V4 | BMI ≥ 30 kg/m2 | NA |
| Ppatil, 2012 [41] | India | Asian | OB | 5 | 5 | 21–62 | Stool | 16s rRNA (not specified) | BMI: 25–53 kg/m2 | NA |
| Rahat-Rozenbloom,2014 [42] | Canada | Caucasian | OB | 11 | 11 | > 17 | Stool | 16s rRNA (V6) | BMI > 25 kg/m2 | NA |
| Riva, 2017 [43] | Italy | Caucasian | OB | 42 | 36 | 9–16 | Stool | 16s rRNA V3–V4 | BMI z-score | NA |
| Vieira-Silva, 2020 [44] | Belgium | Caucasian | OB | 474 | 414 | 18–76 | Stool | Metagenomics | BMI ≥ 30 kg/m2 | NA |
| Ville, 2020 [45] | USA | Hispanic/Latino | OB | 6 | 39 | 0.5–1 | Stool | 16s rRNA V4 | BMI ≥ 95th percentile | NA |
| Yasir, 2015 [46] | France/Saudi Arabia | Caucasian/Asian | OB | 21 | 25 | ≥ 18 | Stool | 16s rRNA (V3–V4) | BMI ≥ 30.0 kg/m2 | NA |
| Yun, 2017 [47] | Korea | Asian | OB | 745 (OB:n = 419; OW: n = 326) | 529 | > 18 | Stool | 16s rRNA V3–V4 | BMI ≥ 25 kg/m2 | NA |
| Zacarias, 2018 [48] | Finland | Caucasian | OB | 29 (OB: n = 11, OW: n = 18) | 25 | NW:29.6 ± 4.2; OW:30.4 ± 3.6; OB:29.6 ± 2.3 | Stool | 16s rRNA V3–V4 | BMI≥30 kg/m2 | NA |
| Allin, 2018 [49] | Denmark | Caucasian | T2DM | 134 | 134 | 55–68 | Stool | 16s rRNA (V4) | NA | Fasting plasma glucose of 6.1–7.0 mmol/l or HbA1c of 42–48 mmol/mol [6.0–6.5%] |
| Barengolts, 2018 [50] | USA | Black | T2DM | 73 | 20 | 35–70 | Stool | 16s rRNA (V3–V4) | NA | HbA1c of 6.5–7.4% |
| Leite, 2017 [51] | Brazil | Hispanic/Latino | T2DM | 20 | 22 | 36–75 | Stool | 16s rRNA (V3–V4) | NA | Fasting blood glucose levels ≥ 126 mg/dL |
| Qin, 2012 [52] | China | Asian | T2DM | 170 | 174 | 25–86 | Stool | Metagenomics | NA | NA |
| Karlsson, 2013 [53] | Sweden | Caucasian | T2DM | 102 | 43 | 70 | Stool | Metagenomics | NA | Glucose metabolism impairment: fasting hyperglycaemia (fasting venous plasma glucose ≥ 6.1 and < 7.0 mmol/L) or IGT (fasting venous plasma glucose <7 mmol/L, ≥ 7.8 and < 11.1 mg/dL 2 h after OGTT) or new onset T2DM (fasting glucose ≥ 7 mmol/L or ≥ 11.1 mmol/L 2 h after OGTT); Arterial hypertension (AH) (systolic/diastolic blood pressure level of 140/90–159/99 mmHg). |
| Larsen, 2010 [54] | Denmark | Caucasian | T2DM | 18 | 18 | 31–73 | Stool | 16s rRNA (V4–V6) | NA | The diabetic group had elevated concentration of plasma glucose as determined by OGTT. Non-diabetic group based on the measurements of baseline glucose and biochemical analysis of blood samples. |
| Ahmad, 2019 [55] | Pakistan | Asian | T2DM | 40 | 20 | 25–55 | Stool | 16s rRNA (V3–V4) | NA | NA |
| Koo, 2019 [56] | China, Malaysia, and India | Asian | T2DM | 22 | 13 | 22–70 | Stool | 16s rRNA (V3–V6) | waist circumference ≥ 90 cm in men and ≥ 80 cm in women | DM were excluded by the absence of impaired glucose tolerance on fasting blood glucose. |
| Sroka-oleksiak, 2020 [57] | Poland | Caucasian | T2DM | OB: n = 17;OB+T2DM: n = 22) | 27 | 20–70 | Duodenal biopsies | 16s rRNA (V3–V4) | BMI >35 kg/m2 | NA |
| Thingholm, 2019 [58] | Germany | Caucasian | T2DM | OB: n = 494;OB+T2DM: n = 153) | 633 | 21–78 | Stool | Metagenomics/16s rRNA (V1–V2) | BMI > 30.0 kg/m2 | Fasting glucose level ≥ 125 mg/dl |
| Zhao, 2019 [59] | China | Asian | NAFLD | OB: n = 18;NAFLD: n = 25) | 15 | 9–17 | Stool | Metagenomics | BMI ≥ 95th percentile | NA |
| Jiang, 2015 [60] | China | Asian | NAFLD | 35 | 30 | 22–72 | Stool | 16s rRNA (V3) | NA | Based on evidence of hepatic steatosis via either imaging or histology |
| Shen, 2017 [61] | Chinese | Asian | NAFLD | 25 | 22 | > 18 | Stool | 16s rRNA (V3–V5) | NA | NAFLD can be diagnosed by the presence of three findings: (i) the histological findings of liver biopsy are in accord with the pathological diagnostic criteria of fatty liver disease. (ii) there is no history of alcohol drinking habit or the ethanol intake per week was less than 140 g in men (70 g in women) in the past 12 months; (iii) specific diseases that could lead to steatosis, such as viral hepatitis, drug-induced liver disease, total parenteral nutrition, Wilson’s disease, and autoimmune liver disease, can be excluded. |
| Sobhonslidsuk, 2018 [62] | Thailand | Asian | NASH | 16 | 8 | NASH:59.8 ± 9.6; control:43.4 ± 6.8 | Stool | 16s rRNA (V3–V4) | NA | NAFLD activity score ≥ 5 |
| Wang, 2016 [63] | China | Asian | NAFLD | 43 | 83 | 33–61 | Stool | 16s rRNA (V3) | NA | Evidence of fatty liver upon ultrasonography |
| Li, 2018 [64] | China | Asian | NAFLD | 30 | 37 | 18–70 | Stool | 16s rRNA (V4) | NA | The diagnosis of NAFLD was based on the following criteria: (i) abdominal ultrasonography indicated a fatty liver; (ii) the patient’s alcohol consumption was less than 20 g/day and 10 g/day for male for female. |
| Nistal, 2019 [65] | Spain | Caucasian | NAFLD | 53 | 20 | 20–60 | Stool | 16S rRNA (V3–V4) | NA | An NAFLD diagnosis was established by clinical, analytical criteria (liver function test) and from ultrasonographic data when steatosis was detected. |
| Yun, 2019 [66] | Korea | Asian | NAFLD | 76 | 192 | 43.6 ± 8.2 | Stool | 16s rRNA (V3–V4) | BMI ≥ 25 kg/m2 | U/S findings suggestive of fatty liver disease |
| Michail, 2015 [67] | USA | Caucasian | NAFLD | 24 | 26 | 13.2 ± 3.8 | Stool | 16s rRNA (not specified) | BMI ≥ 95th percentile | Ultrasound findings and elevated transaminases suggestive of NAFLD |
| Zhu, 2013 [68] | USA | Caucasian | NASH | 47 | 16 | < 18 | Stool | 16s rRNA (not specified) | BMI ≥ 95th percentile | NAFLD activity score≥ 5 |
| Chavez-Carbaja, 2019 [69] | Mexico | Hispanic/Latino | MS | 42 | 25 | 18–59 | Stool | 16s rRNA (V4) | At least three of the following issues: waist greater than 102 cm in males or 82 cm in females, triglycerides levels greater or equal to 150 mg/dl, HDL cholesterol levels less than 40 mg/dl in males or less than 50 mg/dl in females, blood pressure greater or equal to 130/85 mmHg and a fasting blood glucose level higher or equal to 100 mg/dl. | |
| De La Cuesta-Zuluaga, 2018 [70] | Colombia | Hispanic/Latino | MS | 291 | 151 | 18–62 | Stool | 16s rRNA (V4) | BMI ≥ 30.0 kg/m2 | At least two of the following conditions: systolic/diastolic blood pressure ⩾130/85 mm Hg or consumption of antihypertensive medication; fasting triglycerides ⩾150 mg/dl; HDL ≤ 40 mg /dl (men), ≤ 50 mg/dl (women) or consumption of lipid-lowering medication; fasting glucose ⩾ 100 mg/dl or consumption of antidiabetic medication; HOMA-IR 43, and hs-CRP 43 mg L−1. |
| Gallardo-Becerra, 2020 [71] | Mexico | Hispanic/Latino | MS | 17 | 10 | 7–10 | Stool | 16s rRNA (V4) | BMI> 95th percentile | At least two of the following metabolic traits: (1) triglycerides > 1.1 mmol/L (100 mg/dL); (2) HDL cholesterol < 1.3 mmol/L (50 mg/dL); (3) glucose > 6.1 mmol/L (110 mg/dL); (4) systolic blood pressure > 90th percentile for gender, age, and height. |
| Gozd-Barszczewska, 2017 [72] | Poland | Caucasian | MS | 15 | 5 | 45–65 | Stool | 16s rRNA (V3–V5) | BMI ≥ 30.0 kg/m2 | Lipid profile was assessed based on ESC/EAS Guidelines |
| Kashtanova, 2018 [73] | Russia | Caucasian | MS | 57 | 35 | 25–76 | Stool | 16s rRNA (V3–V4) | BMI ≥ 30 kg/m2 and/or waist circumference ≥ 94 cm for men and ≥ 80 cm for women | Glucose metabolism impairment: fasting hyperglycaemia (fasting venous plasma glucose ≥ 6.1 and < 7.0 mmol/L) or IGT (fasting venous plasma glucose < 7 mmol/L, ≥7.8 and < 11.1 mg/dL 2 h after OGTT) or new onset T2DM (fasting glucose ≥ 7 mmol/L or ≥11.1 mmol/L 2 h after OGTT); Arterial hypertension (AH) (systolic/diastolic blood pressure level of 140/90–159/99 mmHg). |
| Lippert, 2017 [74] | Austria | Caucasian | MS | 12 | 8 | 58–71 | Stool | 16s rRNA (V1–V3) | NA | At least two of the following conditions: systolic/diastolic blood pressure ⩾ 130/85 mm Hg or consumption of antihypertensive medication; fasting triglycerides ⩾ 150 mg/dl; HDL ≤ 40 mg/dl (men),≤ 50 mg/dl (women), or consumption of lipid-lowering medication; fasting glucose ⩾ 100 mg/dl or consumption of antidiabetic medication; HOMA-IR 43, and hs-CRP 43 mg L−1. |
| Feinn, 2020 [75] | Italy | Caucasian | NAFLD | 44 | 29 | NAFLD: 13.3 ± 3.2; OB without NAFLD: 12.9 ± 2.8 | Stool | 16s rRNA (V4) | BMI ≥ 95th percentile | Hepatic fat fraction ≥ 5.5% |
| Li, 2021 [76] | China | Asian | OB | 3 | 3 | OB:34.33 ± 0.47; NW:25.67 ± 1.25 | Stool | 16s rRNA (V3–V4) | BMI≥ 30.0 kg/m2 | NA |
| Yuan, 2021 [77] | China | Asian | MS | 65 | 21 | 5–15 | Stool | 16s rRNA (V3–V4) | NA | The presence of at least one of the following metabolic traits: (1) FPG ≥ 5.6 mmol/L; (2) systolic blood pressure ≥ 90th percentile for gender and age; (3) fasting HDL-C < 1.03 mmol/L; and (4) fasting TG ≥ 1.7 mmol/L. |
OW overweight, OB obesity, T2DM diabetes mellitus type 2, NAFLD non-alcoholic fatty liver disease, MS metabolic syndrome, NASH non-alcoholic steatohepatitis, NA not appliable, IGT impaired glucose tolerance
*Refers to a standard developed by the Department of Growth and Development, Capital Institution of Pediatrics, China, to define children of obesity