Effect of metformin on metabolic improvement and gut microbiota

From BugSigDB
Needs review
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
Authors
Lee H, Ko G
Journal
Applied and environmental microbiology
Year
2014
Metformin is commonly used as the first line of medication for the treatment of metabolic syndromes, such as obesity and type 2 diabetes (T2D). Recently, metformin-induced changes in the gut microbiota have been reported; however, the relationship between metformin treatment and the gut microbiota remains unclear. In this study, the composition of the gut microbiota was investigated using a mouse model of high-fat-diet (HFD)-induced obesity with and without metformin treatment. As expected, metformin treatment improved markers of metabolic disorders, including serum glucose levels, body weight, and total cholesterol levels. Moreover, Akkermansia muciniphila (12.44%±5.26%) and Clostridium cocleatum (0.10%±0.09%) abundances increased significantly after metformin treatment of mice on the HFD. The relative abundance of A. muciniphila in the fecal microbiota was also found to increase in brain heart infusion (BHI) medium supplemented with metformin in vitro. In addition to the changes in the microbiota associated with metformin treatment, when other influences were controlled for, a total of 18 KEGG metabolic pathways (including those for sphingolipid and fatty acid metabolism) were significantly upregulated in the gut microbiota during metformin treatment of mice on an HFD. Our results demonstrate that the gut microbiota and their metabolic pathways are influenced by metformin treatment.

Experiment 1


Needs review

Curated date: 2025/02/13

Curator: Aleru Divine

Revision editor(s): Aleru Divine, WikiWorks

Subjects

Location of subjects
South Korea
Host species Species from which microbiome was sampled. Contact us to have more species added.
Mus musculus
Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
Feces Cow dung,Cow pat,Droppings,Dung,Excrement,Excreta,Faeces,Fecal material,Fecal matter,Fewmet,Frass,Guano,Matières fécales@fr,Merde@fr,Ordure,Partie de la merde@fr,Piece of shit,Porción de mierda@es,Portion of dung,Portion of excrement,Portion of faeces,Portion of fecal material,Portion of fecal matter,Portion of feces,Portion of guano,Portion of scat,Portionem cacas,Scat,Spoor,Spraint,Stool,Teil der fäkalien@de,Feces,feces
Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Group 0 name Corresponds to the control (unexposed) group for case-control studies
High-Fat-Diet to Normal Diet group (HFD-ND) and High-Fat-Diet + Metformin group (HFD-Met)
Group 1 name Corresponds to the case (exposed) group for case-control studies
High-Fat-Diet group (HFD)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Group of mice receiving HFD without metformin treatment (HFD group).

Lab analysis

Sequencing type
16S
16S variable region One or more hypervariable region(s) of the bacterial 16S gene
V1-V3
Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
Roche454

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
relative abundances
Statistical test
LEfSe
Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
0.05
MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
No
LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
4.0
Matched on Factors on which subjects have been matched on in a case-control study
age, sex


Signature 1

Needs review

Curated date: 2025/02/13

Curator: Aleru Divine

Revision editor(s): Aleru Divine, WikiWorks

Source: Figure 4E

Description: Microbial difference in the bacterial community between groups categorized according to diet and metformin treatment.

Abundance in Group 1: increased abundance in High-Fat-Diet group (HFD)

NCBI Quality ControlLinks
Clostridium
Dehalobacterium
Lachnospiraceae
Oscillospira
Oscillospira guilliermondii
Peptococcaceae
unclassified Clostridium
unclassified Lachnospiraceae
unclassified Oscillospiraceae
DehalobacteriaceaeDehalobacteriaceae

Revision editor(s): Aleru Divine, WikiWorks

Experiment 2


Needs review

Curated date: 2025/02/13

Curator: Aleru Divine

Revision editor(s): Aleru Divine, WikiWorks

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
High-Fat-Diet group (HFD) and High-Fat-Diet + Metformin group (HFD-Met)
Group 1 name Corresponds to the case (exposed) group for case-control studies
High-Fat-Diet to Normal Diet group (HFD-ND)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Group of mice that received a dietary change from a High-Fat-Diet to Normal Diet group (HFD-ND).

Lab analysis

Statistical Analysis

Signature 1

Needs review

Curated date: 2025/02/13

Curator: Aleru Divine

Revision editor(s): Aleru Divine, WikiWorks

Source: Figure 4E

Description: Microbial difference in the bacterial community between groups categorized according to diet and metformin treatment.

Abundance in Group 1: increased abundance in High-Fat-Diet to Normal Diet group (HFD-ND)

NCBI Quality ControlLinks
Akkermansia
Akkermansia muciniphila
Bacteroidaceae
Clostridium
Eubacteriales Family XIII. Incertae Sedis
Thomasclavelia cocleata
Verrucomicrobiaceae
unclassified Bacteroides

Revision editor(s): Aleru Divine, WikiWorks

Experiment 3


Needs review

Curated date: 2025/02/13

Curator: Aleru Divine

Revision editor(s): Aleru Divine, WikiWorks

Differences from previous experiment shown

Subjects

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Response to metformin Response to metformin,response to metformin
Group 0 name Corresponds to the control (unexposed) group for case-control studies
High-Fat-Diet to Normal Diet group (HFD-ND) and High-Fat-Diet group (HFD)
Group 1 name Corresponds to the case (exposed) group for case-control studies
High-Fat-Diet + Metformin group (HFD-Met)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Group of mice that had Metformin (300 mg/kg of body weight 1,1-dimethylbiguanide hydrochloride; Sigma-Aldrich) administered every day during the HFD for 10 weeks (HFD-Met group).

Lab analysis

Statistical Analysis

Signature 1

Needs review

Curated date: 2025/02/13

Curator: Aleru Divine

Revision editor(s): Aleru Divine, WikiWorks

Source: Figure 4E

Description: Microbial difference in the bacterial community between groups categorized according to diet and metformin treatment.

Abundance in Group 1: increased abundance in High-Fat-Diet + Metformin group (HFD-Met)

NCBI Quality ControlLinks
Alistipes
Rikenellaceae

Revision editor(s): Aleru Divine, WikiWorks

Experiment 4


Needs review

Curated date: 2025/02/13

Curator: Aleru Divine

Revision editor(s): Aleru Divine, WikiWorks

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Normal Diet group (ND)
Group 1 name Corresponds to the case (exposed) group for case-control studies
Normal Diet + Met group(ND-Met)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Group of mice receiving Normal Diet (ND) with metformin treatment (ND-Met).

Lab analysis

Statistical Analysis

Signature 1

Needs review

Curated date: 2025/02/13

Curator: Aleru Divine

Revision editor(s): Aleru Divine, WikiWorks

Source: Figure 4F

Description: Microbial difference in the bacterial community between groups categorized according to diet and metformin treatment.

Abundance in Group 1: increased abundance in Normal Diet + Met group(ND-Met)

NCBI Quality ControlLinks
Alistipes
Rikenellaceae
Flavonifractor plautii
Clostridium
unclassified Oscillospiraceae
Verrucomicrobiaceae
Akkermansia muciniphila
Akkermansia

Revision editor(s): Aleru Divine, WikiWorks

Signature 2

Needs review

Curated date: 2025/02/13

Curator: Aleru Divine

Revision editor(s): Aleru Divine, WikiWorks

Source: Figure 4F

Description: Microbial difference in the bacterial community between groups categorized according to diet and metformin treatment.

Abundance in Group 1: decreased abundance in Normal Diet + Met group(ND-Met)

NCBI Quality ControlLinks
Lactobacillus iners
Lactobacillus
Lactobacillaceae

Revision editor(s): Aleru Divine, WikiWorks

Experiment 5


Needs review

Curated date: 2025/02/13

Curator: Aleru Divine

Revision editor(s): Aleru Divine, WikiWorks

Differences from previous experiment shown

Subjects

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Male mice
Group 1 name Corresponds to the case (exposed) group for case-control studies
Female mice
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Group of female mice on High-Fat-Diet (HFD).

Lab analysis

Statistical Analysis

LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
3.0


Signature 1

Needs review

Curated date: 2025/02/13

Curator: Aleru Divine

Revision editor(s): Aleru Divine, WikiWorks

Source: Figure 5A

Description: Differences in the gut microbiota between male and female mice in the HFD group.

Abundance in Group 1: increased abundance in Female mice

NCBI Quality ControlLinks
Bacteria
unclassified Bacteroides
Bacteroidota
Bacteroidaceae

Revision editor(s): Aleru Divine, WikiWorks

Signature 2

Needs review

Curated date: 2025/02/13

Curator: Aleru Divine

Revision editor(s): Aleru Divine, WikiWorks

Source: Figure 5A

Description: Differences in the gut microbiota between male and female mice in the HFD group.

Abundance in Group 1: decreased abundance in Female mice

NCBI Quality ControlLinks
Bacillota
Lachnospiraceae
unclassified Lachnospiraceae
Mycoplasmatota
DehalobacteriaceaeDehalobacteriaceae
Dehalobacterium
Oscillospira
Erysipelotrichia
Bacilli
Lactobacillaceae
Erysipelotrichaceae
unclassified Clostridia
unclassified Lactobacillus
Lactobacillus iners
unclassified Erysipelotrichaceae
Allobaculum sp.
Allobaculum
Lactobacillus

Revision editor(s): Aleru Divine, WikiWorks

Experiment 6


Needs review

Curated date: 2025/02/13

Curator: Aleru Divine

Revision editor(s): Aleru Divine, WikiWorks

Differences from previous experiment shown

Subjects

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Response to metformin Response to metformin,response to metformin
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Group of female mice that were administered Metformin (300 mg/kg of body weight 1,1-dimethylbiguanide hydrochloride; Sigma-Aldrich) every day during the HFD for 10 weeks (HFD-Met group).

Lab analysis

Statistical Analysis

Signature 1

Needs review

Curated date: 2025/02/13

Curator: Aleru Divine

Revision editor(s): Aleru Divine, WikiWorks

Source: Figure 5B

Description: Differences in the gut microbiota between male and female mice in the HFD-Met group.

Abundance in Group 1: increased abundance in Female mice

NCBI Quality ControlLinks
Bacteroidia
Lactobacillaceae
Bacteroides
Clostridium
Flavonifractor plautii

Revision editor(s): Aleru Divine, WikiWorks

Signature 2

Needs review

Curated date: 2025/02/13

Curator: Aleru Divine

Revision editor(s): Aleru Divine, WikiWorks

Source: Figure 5B

Description: Differences in the gut microbiota between male and female mice in the HFD-Met group.

Abundance in Group 1: decreased abundance in Female mice

NCBI Quality ControlLinks
unclassified Coprobacillus

Revision editor(s): Aleru Divine, WikiWorks

Experiment 7


Needs review

Curated date: 2025/02/13

Curator: Aleru Divine

Revision editor(s): Aleru Divine, WikiWorks

Differences from previous experiment shown

Subjects

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Group of female mice that received a dietary change from a High-Fat-Diet to Normal Diet group (HFD-ND).

Lab analysis

Statistical Analysis

Signature 1

Needs review

Curated date: 2025/02/13

Curator: Aleru Divine

Revision editor(s): Aleru Divine, WikiWorks

Source: Figure 5C

Description: Differences in the gut microbiota between male and female mice in the HFD-ND group.

Abundance in Group 1: decreased abundance in Female mice

NCBI Quality ControlLinks
Mollicutes
Mycoplasmatota

Revision editor(s): Aleru Divine, WikiWorks

Experiment 8


Needs review

Curated date: 2025/02/13

Curator: Aleru Divine

Revision editor(s): Aleru Divine, WikiWorks

Differences from previous experiment shown

Subjects

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Group of female mice receiving Normal Diet (ND).

Lab analysis

Statistical Analysis

Signature 1

Needs review

Curated date: 2025/02/13

Curator: Aleru Divine

Revision editor(s): Aleru Divine, WikiWorks

Source: Figure 5D

Description: Differences in the gut microbiota between male and female mice in the ND group.

Abundance in Group 1: increased abundance in Female mice

NCBI Quality ControlLinks
unclassified Erysipelotrichaceae
Porphyromonadaceae
Parabacteroides

Revision editor(s): Aleru Divine, WikiWorks