Table 1.
Alteration in microbiota composition and biochemical variables in human studies.
| Study | Country | Type of study | Sample size | Age | Diagnostic tool | Medication | Microbiota analysis | Biochemical analysis | Main study findings (Microbiota profile) | Biochemical changes | Quality assessment score | ||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Gout patients | Control | Gout patients | control | ||||||||||
| Méndez-Salazar et al. (14) | Mexico | Case-control | 58 (33 with a tophi and 25 without tophi) | 53 | Not mentioned | Not mentioned | 2015 ACR/EULAR (23) | No antibiotics, or anti-parasitic, other medication were not mentioned | Sequencing hypervariable V3–V4 regions of the bacterial 16S rRNA genes (Illumina Miseq platform) | Analysis of blood sample | Richness indices: Chao1 ↑ Observed species ↑ ACE ↑ in controls. In controls Genera: Ruminococcus_ 1 ↑, Clostridium_ sensu_ stricto_ 1 ↑Oscillibacter ↑, Butyricicoccus ↑, Ruminococcaceae_ UCG_ 010 ↑, Bifdobacterium ↑, Lachnospiraceae_ ND3007_ group↑, Haemophilus ↑ and Ruminococcaceae_ UGC_ 013 ↑In gout without tophi Genera: Phascolarctobacterium ↑, Akkermansia ↑, Bacteroides ↑ and Ruminococcus_ gnavus_ group ↑ from controls and Lachnospira ↑, Erysipelotrichaceae_ UCG_ 003 ↑, Roseburia ↑, Ruminococcaceae_ UGC_ 013 ↑ Erysipelotrichaceae_ UCG_ 003 ↑ and Akkermansia ↑ from gout with tophi In gout with tophi Phylum: Proteobacteria ↑ Genera: Escherichia-Shigella ↑ From controls and Genera: Sarcina ↑, | In controls: Urea carboxylase ↑ and urease accessory protein ↑ In gout without tophi: glycine reductase complex component B subunits alpha, beta and gamma ↑ and Glycine dehydrogenase subunit ↑ In gout with tophi: Vitamin B12 (permease protein and substrate binding protein) ↑, Nucleoside permease ↑, Xanthine phosphorylases ↑, Nucleoside phosphorylases ↑, Methionine transaminase ↑, | 6/9 |
| Rikenellaceae_ RC9 ↑, Lachnospiraceae_ NK4B4 ↑ and Lachnospiraceae_ ND3007 ↑ From gout without tophi. | Glycine cleavage system transcriptional repressor ↑, Xanthine dehydrogenase iron-sulfur-binding subunits↑, 5-hydroxyisourate hydrolase ↑, (S)-ureidoglycine aminohydralase ↑ and purine nucleosidase ↑ | ||||||||||||
| Chu et al. (4) | China | Nested case-control | 102 (77 discovery gout + 25 validation gout) | 86 (63 discovery control + 23 validation control) | Discovery= 39.9 ± 12.9 Validation= 41.9 ± 14.4 | Discovery= 40.0 ± 12.1 Validation= 38.3 ± 13.6 | 2015 ACR/EULAR (23) | No antibiotics and glucocorticoid use within 3 months and 1 month for patients and controls | Metagenomic shotgun sequencing | Analysis of blood sample | Phylum: Bacteroidetes ↑, Fusobacteria ↑ Proteobacteria ↓Species: 3 species of Bacteroides ↑ 13 species of Prevotella ↑ 4 species of Fusobacterium ↑ | ESR ↑, CRP ↑, SCr ↑ and SUA ↑ In gout patients than controls | 5/9 |
| Yang et al. (24) | China | Cross-sectional | 45 patients with AH 45 cases in the control group (57: Male, 33: Female) | 60 (49–66.25 years) | Index of the blood uric acid was more than 360 μmol/L (for woman), or more than 420 μmol/L (for man) in two fasting blood uric acid determinations on separate days | No antibiotic antibiotics or probiotics within 3 months | PCR amplification of the V3-V4 region of 16S rRNA genes | Analysis of blood lipid, routine blood testing parameters, blood biochemical analysis, liver function parameters and renal function parameters | α-diversity: Chao1 index ↑ Ace index ↑ Shannon index ↑ In AH group Genera: unclassified_ Ruminococcaceae ↑, Alistipes ↑, Dialister ↑, unidentified_ Ruminococcaceae ↑, Roseburia ↑, Gemmiger ↑, and Faecalibacterium ↑ in AH group unclassified_ Enterobacteriaceae ↑, Bifidobacterium ↑, Klebsiella ↑, Ruminococcus ↑, unidentified_ Lactobacillales ↑, unclassified_ Enterococcaceae ↑, Eubacterium ↑, unidentified_ Enterobacteriaceae ↑, and Clostridium ↑ in control group | NA | 6/7 | ||
| Lin et al. (8) | China | Nested case-control | 38 patients 26 healthy participants Both gout patients and healthy controls were from local inhabitants with the same gender and similar age | (23), elevation of uric acid and typical clinical manifestations | No anti-gout drugs, steroids, proton pump inhibitors, nonsteroidal anti-inflammatory drugs, Traditional Chinese medicine or any other drugs in three months before admission to the study. | metagenomic shotgun sequencing and 16S rRNA genes sequencing | N/A | Phylum: Actinobacteria ↑ in healthy controls and Firmicutes ↑ in untreated patients from HCs Genera: Fecalibacterium ↑, Lachnospiraceae Clostridium ↑, Roseburia ↑, Cytophaga ↑, Ruminococcaceae Clostridium ↑, Alistipes ↑, Pseudomonas ↑, Butyricicoccus ↑, Clostridiaceae Clostridium ↑, Sporobacter ↑, Campylobacter ↑, Desulfotomaculum ↑, Halomonas and Succinispira ↑ in untreated patients from HCs Millisia ↑, Bifidobacterium ↑, Paracoccus ↑, Aeromonas ↑, Enterococcus ↑ and Leifsonia ↑ in HCs | NA | 6/9 | |||
| Henson et al. (11) | USA | Case-control | 41 (24: Male, 17: Female) | 42 (25: Male, 17:Female) | 49.4 | 48.7 | clinical symptoms and elevated blood uric acid levels | Not mentioned | 16S rRNA gene amplicon library sequencing. | N/A | Faecalibacterium ↑ in the healthy samples | BUN ↑ In gout patients Butyrate ↑, L-lactate ↑, L-cysteine ↑, L-methionine ↑, H2S ↑, L-isoleucine ↑, 3-methyl-2-oxovaleric acid ↑, L-histidine ↑ and L-tyrosine ↑ In low gout cluster Alanine ↑, H2 ↑, Isobutyrate ↑, Isocaproate ↑ and Isovalerate ↑ In high gout cluster | 4/9 |
| Ning et al. (3) | China | Nested case-control | 30 (Male) | 30 (Male) | 45.86 | 41.36 | 2015 ACR/EULAR (23) | No antibiotics within 1 month, other mediction were not mentioned | PCR Amplification of the Bacterial 16S rRNA V3–V4 Region and Illumina Pyrosequencing | N/A | α-diversity: ACE index ↓ Chao1 index ↓ Shannon index ↓ Simpson index ↓ observed-species index ↓ in gout group Phylum: Firmicutes ↑, Actinobacteria ↑ and Proteobacteria ↓ in gout patients Genera: Corynebacterium_ 1 ↑, Prevotella ↑ and Novosphingobium ↓, Derxia ↓, Curvibacter ↓, Methylobacterium ↓, Caulobacter ↓, Skermanella ↓ unidentified_ Chloroplast ↓ and Rikenellaceae_ RC9_ gut_ group ↓ in gout patients | UA serum levels ↑ and BUN ↑ In gout patients | 7/9 |
| Liu et al. (5) | China | Nested case-control | 12 gout patients (8: Male, 4: Female) + 11 (9: Male, 2: Female) HUA patients | 19 (15: Male, 4: Female) | 54.42 years for gout patients 53.5 years for HUA patients | 55.95 | NA | Only subjects with a non-smoking history | 16S rDNA sequencing (Illumina HiSeq 2000 platform) | N/A | Species: Prevotella intermedia ↑and Streptococcus anginosus ↑ in HUA and gout patients Serratia marcescens ↑ in HCs | NA | 2/9 |
| Shao et al. (2) | China | Case-control | 26 (Male) | 26 (Male) | 43.60 | 39.42 | The clinical diagnosis and blood examination reports | Patients: No medical treatment within 1 month of study participation, healthy controls: No antibiotics within 1 month of this study | PCR amplification of the V3-V4 region of 16S rRNA genes | 1H NMR spectra assaying | α-diversity: Chao1 ↓, Observed species ↓, Simpson ↓ and Shannon ↓ in gout patients In gout patients Phylum: Chloroflexi ↑, Bacteroidetes ↑Class: Erysipelotrichia ↑, Negativicutes ↑, Anaerolineae ↑ and Bacteroidia ↑Order: Bacteroidales ↑, Anaerolineales ↑, Selenomonadales ↑, Corynebacteriales ↑and Erysipelotrichales ↑ Family: Nocardiaceae ↑, Bacteroidaceae ↑, Anaerolineaceae ↑, Porphyromonadaceae ↑, Erysipelotrichaceae ↑ and Vibrionaceae ↓ Genus: Rhodococcus ↑, Erysipelatoclostridium ↑ and Photobacterium ↓, Vibrio ↓, Coprococcus 3 ↓, Lachnospiraceae NC2004 group ↓, Lachnospiraceae UCG_ 005 ↓, Ruminococcaceae NK4A214 group ↓ and Ruminococcaceae UCG_ 011 ↓ | ESR ↑, UA ↑ and BUN ↑ Alanine ↑, Glycine ↑, Taurine ↑, Succinate ↑, Acetate ↑, α-glucose ↑, β-glucose ↑, α-xylose ↑ valine ↓, asparagine ↓, aspartate ↓, citrulline ↓, phenylalanine ↓ and α-ketoisocaproate ↓ In gout patients | 5/9 |
| Guo et al. (1) | China | Cohort | 35 gout + 6 validation gout | 33 + 9 validation control | 32–75 years (validation gout =28-69) | aged 28–70 years (validation control = 28-69) | The analysis of blood uric acid for patients with painful joints | Not mentioned | PCR amplification of the bacterial 16S rRNA genes V1-V3 region and pyrosequencing. | N/A | Genera: Coprococcus ↑, Faecalibacterium ↑, Alistipes ↑, Dialister ↑, Robinsoniella ↑, Subdoligranulum ↑, Odoribacter ↑ and Oscillibacter ↑ in controls Barnesiella ↑, Parasporobacterium ↑, Paraprevotella ↑, Anaerotruncus ↑, Pseudobutyrivibrio ↑, Bacteroides ↑, Holdemania ↑ and Acetanaerobacterium ↑ in gout patients Species: Faecalibacterium prausnitzii ↑ and Bifidobacterium ↑ pseudocatenulatum ↑ In healthy individuals Bacteroides caccae ↑ and Bacteroides xylanisolvens ↑ in gout patients | Blood uric acid value ↑ in gout patients | 5/9 |
| Xing et al. (10) | China | Case-Control | 90 (Male) | 94 (Male) | 47.5 years (40 to 60 years) | 49.19 (40 to 60 years) | ACR (American College of Rheumatology) in 1977 | No antibiotics or flora products for 1 month before the sample taking | 16S rRNA specific primers of both Bacteroides and Clostridium adopted for the PCR amplification. | Analysis of blood sample | The Diversity Analysis: Bacteroides the two groups Shannon–Weaver (H' index) and had no statistical significance Clostridium the numbers of Clostridium strips and the H' index were much lower in the gout group than the normal control group with statistical significance The Clustering Analysis: Bacteroides the normal samples in clustering analysis gathered into 1–2 clusters and the similarity was high. However, the clusters in the primary gout group distributed more dispersed, less clustering with lower similarity Clostridium The clustering analysis result that there were about 2/4–3/4 of the normal control samples gathered into 1–2 clusters, the clusters in the primary group distributed more dispersed, less clustering with lower similarity | Bacteroides UA ↑ In gout patients | 7/9 |
| Analysis of blood sample | Clostridium UA ↑ In gout patients | ||||||||||||
NA, not available; HUA, hyperuricemia; HC, healthy controls; ESR, erythrocyte sedimentation rate; UA, uric acid; SCr, serum creatinine; CRP, C-reactive protein; BUN, blood urea nitrogen.