PMID- 35046817
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220121
IS  - 1663-9812 (Print)
IS  - 1663-9812 (Electronic)
IS  - 1663-9812 (Linking)
VI  - 12
DP  - 2021
TI  - Comparative Evaluation of the Effect of Metformin and Insulin on Gut Microbiota 
      and Metabolome Profiles of Type 2 Diabetic Rats Induced by the Combination of 
      Streptozotocin and High-Fat Diet.
PG  - 794103
LID - 10.3389/fphar.2021.794103 [doi]
LID - 794103
AB  - Lately, an increasing number of studies have investigated the relationship 
      between metformin and gut microbiota, suggesting that metformin exerts part of 
      its hypoglycemic effect through the microbes. However, its underlying mechanism 
      remains largely undetermined. In the present study, we investigated the effects 
      of metformin on gut microbiota and metabolome profiles in serum and compared it 
      with insulin treatment in rats with type 2 diabetes mellitus (T2DM). Diabetic 
      rats (DM group) were induced by a combination of streptozotocin and high-fat diet 
      (HFD). After 7 days, DM rats were treated with metformin (MET group) or insulin 
      (INS group) for 3 weeks. The 16S rRNA sequencing of the gut microbiota and 
      non-targeted metabolomics analysis of serum were conducted. A total of 13 bile 
      acids (BAs) in serum were further determined and compared among different groups. 
      The rat model of T2DM was well established with the typical diabetic symptoms, 
      showing significantly increased blood glucose, AUC of OGTT, HOMA-IR, TC, TG, 
      LDL-C and TBA. Metformin or insulin treatment could ameliorate symptoms of 
      diabetes and partly recover the abnormal biochemical indicators. Compared with DM 
      rats, the relative abundances of 13 genera were significantly changed after 
      metformin treatment, while only three genera were changed after insulin 
      treatment. The metformin and insulin treatments also exhibited different serum 
      metabolome profiles in T2DM rats. Moreover, 64 differential metabolites were 
      identified between MET and DM groups, whereas 206 were identified between INS and 
      DM groups. Insulin treatment showed greater influence on amino acids, 
      glycerophospholipids/glycerolipids, and acylcarnitine compared with the metformin 
      treatment, while metformin had an important impact on BAs. Furthermore, metformin 
      could significantly decrease the serum levels of CA, GCA, UDCA, and GUDCA, but 
      increase the level of TLCA in DM rats. Insulin treatment significantly decreased 
      the levels of CA, UDCA, and CDCA. Besides, several metabolites in serum or 
      microbiota were positively or negatively correlated with some bacteria. 
      Collectively, our findings indicated that metformin had a stronger effect on gut 
      microbiota than insulin, while insulin treatment showed greater influence on 
      serum metabolites, which provided novel insights into the therapeutic effects of 
      metformin on diabetes.
CI  - Copyright (c) 2022 Hu, Zhang, Wang, Yang, Jiang, Chen and Wang.
FAU - Hu, Nan
AU  - Hu N
AD  - Department of Pharmacy, The Third Affiliated Hospital of Soochow University/The 
      First People's Hospital of Changzhou, Changzhou, China.
FAU - Zhang, Qi
AU  - Zhang Q
AD  - Department of Pharmacy, Changzhou No. 7 People's Hospital, Changzhou, China.
FAU - Wang, Hui
AU  - Wang H
AD  - Department of Pathology, The Third Affiliated Hospital of Soochow University/The 
      First People's Hospital of Changzhou, Changzhou, China.
FAU - Yang, Xuping
AU  - Yang X
AD  - Department of Pharmacy, The Third Affiliated Hospital of Soochow University/The 
      First People's Hospital of Changzhou, Changzhou, China.
FAU - Jiang, Yan
AU  - Jiang Y
AD  - Department of Pharmacy, The Third Affiliated Hospital of Soochow University/The 
      First People's Hospital of Changzhou, Changzhou, China.
FAU - Chen, Rong
AU  - Chen R
AD  - Department of Pharmacy, The Third Affiliated Hospital of Soochow University/The 
      First People's Hospital of Changzhou, Changzhou, China.
FAU - Wang, Liying
AU  - Wang L
AD  - Department of Pharmacy, The Third Affiliated Hospital of Soochow University/The 
      First People's Hospital of Changzhou, Changzhou, China.
LA  - eng
PT  - Journal Article
DEP - 20220103
PL  - Switzerland
TA  - Front Pharmacol
JT  - Frontiers in pharmacology
JID - 101548923
PMC - PMC8762251
OTO - NOTNLM
OT  - bile acids
OT  - insulin
OT  - metabolome
OT  - metformin
OT  - microbiota
OT  - type 2 diabetes
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/01/21 06:00
MHDA- 2022/01/21 06:01
PMCR- 2022/01/03
CRDT- 2022/01/20 06:01
PHST- 2021/10/13 00:00 [received]
PHST- 2021/11/22 00:00 [accepted]
PHST- 2022/01/20 06:01 [entrez]
PHST- 2022/01/21 06:00 [pubmed]
PHST- 2022/01/21 06:01 [medline]
PHST- 2022/01/03 00:00 [pmc-release]
AID - 794103 [pii]
AID - 10.3389/fphar.2021.794103 [doi]
PST - epublish
SO  - Front Pharmacol. 2022 Jan 3;12:794103. doi: 10.3389/fphar.2021.794103. 
      eCollection 2021.