Table 1.
The Effects of Metformin on Composition of Gut Microbiota in T2DM or Obese Mice
| Animal Model | Control Group (Number) | Metformin Treatment Group (Number) | Effect of Metformin on Gut Microbiota | Country | Method for Detection | Author, Year and References | |
|---|---|---|---|---|---|---|---|
| 1 | C57BL/6 mice (4 weeks old) | HFD for 8 weeks + HFD for 6 weeks (n=6) | HFD for 8 weeks + HFD with metformin treatment (300mg/kg/d) for 6 weeks (n=6) | Phylum: Verrucomicrobia↑ Genus: Akkermansia↑ | Korea | 16S rRNA | Shin et al 201426 |
| 2 | C57BL/6 mice (6 weeks old) | HFD for 18weeks + HFD for 10weeks (n=N/A) | HFD for 18weeks + HFD with metformin treatment (300mg/kg/d) for 10weeks (n=N/A) | Phylum: Bacteroidetes↑, Verrucomicrobia↑ Family: Bacteroidaceae↑, Verrucomicrobiaceae↑, Clostridiales family XIII↑ Species: Akkermansia muciniphila↑, Clostridium cocleatum↑ | Korea | 16S rRNA, qPCR | Lee et al 201427 |
| 3 | C57BL/6J mice (3 weeks old) | HFD for 12 weeks + HDF for 6 weeks (n=3) | HFD for 12 weeks + HFD with metformin treatment (300mg/kg/d) for 6 weeks (n=3) | Genus: Lactococcus, Coprococcus, Ruminococcus, Staphylococcus, Akkermansia, Streptococcus, Oscillospira, Lactobacillus, Allobaculum, Clostridium, Dorea changed | USA | 16S rRNA, | Bornstein et al 201728 |
| 4 | Obese diabetic db/db mice (8 weeks old) | Distilled water for 8 weeks (n=10) | Metformin treatment(20mg/kg/d) for 8 weeks (n=10) | Genus: Bacteroidales↑, Lactobacillus↑, Allobaculum↑, Bacteroides↑, Akkermansia↑, Staphylococcus↓, Corynebacterium↓, Jeotgalicoccus↓, Aerococcus↓, Enterococcus↓, Facklamia↓ | China | 16S rRNA | Chen et al 201837 |
| 5 | C57BL/6N mice (6 weeks old) | HFD for 23 weeks + HFD for 16 weeks (n=6) | HFD for 23weeks + HFD with metformin treatment (250mg/kg/d) for 16 weeks (n=6) | Phylum: Verrucomicrobia↑, Firmicutes/Bacteroidetes ratio↓ Genus: Akkermansia↑, Bacteroides↑, Butyricimonas↑, Parabacteroides↑ | Korea | 16S rRNA, qPCR | Lee et al 201829 |
| 6 | KKAy mice (8–9 weeks old) | HFD for 3 weeks + HFD with saline solution for 8 weeks (n=6) | HFD for 3 weeks + HFD with metformin treatment (314mg/kg/d) for 8 weeks (n=6) | Phylum: Bacteroidetes↑, Verrucomicrobia↑, Actinobacteria↓, Firmicutes↓ Genus: Bacteroides↑, Blautia↑, Escherichia_Shigella↑, Akkermansia↑, Aerococcus↓, Lactobacillus↓, Corynebacterium_1↓, Staphylococcus↓ | China | 16S rRNA | Gao et al 201839 |
| 7 | C57BL/6J mice | HFD for 4 weeks + HFD for 10 weeks (n=8) | HFD for 4 weeks + HFD with metformin treatment (100mg/kg/d) for 10 weeks (n=8) | Species: Bacteriodetes fragilis↑, Escherichia coli↓ | Korea | 16S rRNA, qPCR | Wang et al 201830 |
| 8 | C57BL/6J mice (3 weeks old) | HFD for 4 weeks + STZ+ HFD with saline for 5 weeks (n=6) | HFD for 4 weeks + STZ + HFD with metformin treatment (200mg/kg/d or 75mg/kg/d) for 5 weeks (n=6) | Phylum: Firmicutes↓ Genus: Akkermansia↑ Species: Bacteroides spp.↓ | China | 16S rRNA | Zheng et al 201831 |
| 9 | C57BL/6J mice (6 weeks old) | HFD with saline for 3 weeks (n=5) | HFD with metformin treatment (300mg/kg/d) 3 weeks (n=5) | Genus: Enterococcus, Lactococcus, Streptococcus, Akkermansia changed | China | 16S rRNA | Ji et al 201932 |
| 10 | db/db mice (8 weeks old) | Saline solution for 11 weeks (n=5) | Metformin treatment (113.75mg/kg/d) for 11 weeks (n=5) | Genus: Butyricimonas↑, Lactobacillus↑, Coprococcus↑, Ruminococcus↑, Akkermansia↑ Genus: Prevotella↓, Proteus↓ | China | 16S rRNA, qPCR | Zhang et al 201938 |
| 11 | ICR mice (8 weeks old) | HFD+STZ+HFD for 4 weeks (n=10) | HFD+STZ+HFD with metformin treatment (200mg/kg/d) for 4 weeks (n=10) | Phylum: Firmicutes↑, Bacteroidetes↓, Proteobacteria↓ Species: Lactobacillus spp.↑, Lactobacillales↑ | China | 16S rRNA | Chen et al 201940 |
| 12 | C57BL/6J mice (6–8 weeks old) | FFC for 4 days (n=6) | FFC with metformin treatment (300mg/kg/d) for 4 days (n=6) | Species: Lactobacillus animalis↓, Unclassifed members of Burkholderia and Romboutsia genera↓, An unclassified member of Alloprevotella family↓ | Austria | 16S rRNA | Brandt et al 201933 |
| 13 | C57BL/6 mice (3 weeks old) | HFD for 12 weeks + HFD for 12 weeks (n=14) | HFD for 12 weeks + HFD with metformin treatment (300mg/kg/d) for 12 weeks (n=14) | Phylum: Bacteroidetes↑, Verrucomicrobia↑, Firmicutes/Bacteroidetes ratio↓ Genus: Bacteroides↑, Akkermansia↑, Parabacteroides↑, Christensenella↑, Clostridiales other↑, AF-12↓, Muribaculum↓, Clostridiaceae other↓, Lachnoclostridium↓, Coprococcus↓, Dorea↓, Papillibacter↓, Oscillospira↓, Ruminococcus↓, Desulfovibrio↓, Desulfovibrionaceae↓ | Ireland | 16S rRNA | Ryan et al 202034 |
| 14 | C57BL/6J mice (5 weeks old) | HFD for 14 weeks (n=12) | HFD with metformin treatment (200mg/kg/d) for 14 weeks (n=12) | Family: Lachnospiraceae↓ | USA | 16S rRNA | Chung et al 202035 |
| 15 | C57BL/6J mice (78 weeks old) | HFD for 11 weeks (n=5–7) | HFD with metformin treatment (100mg/kg/d) for 11 weeks (n=5–7) | Phylum: Bacteroidetes↑ Genus: Genera belonging to S24_7, Ruminococcaceae, and Lactococcus↑, Genera belonging to Veilonellaceae, Coriobacteriaceae, Lactobacillus, Dorea, SMB53, Roseburia, and Dehalobacterium↓ | USA | 16S rRNA | Ahmadi et al 202036 |
Notes: ↑, Increase; ↓, decrease.
Abbreviations: N/A, not available; STZ, streptozotozin; HFD, high-fat diet; FFC, fat-fructose- and cholesterol-rich diet.