Effects of Oral Glucose-Lowering Agents on Gut Microbiota and Microbial Metabolites

Wang, Dongmei; Liu, Jieying; Zhou, Liyuan; Zhang, Qian; Li, Ming; Xiao, Xinhua

doi:10.3389/fendo.2022.905171

Cited by 11 publications

(14 citation statements)

References 175 publications

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“…In gut, metformin increases glucose uptake, glycolytic lactate production, glucagon-like peptide-1 (GLP-1) secretion and bile acid pool in addition to microbiome alterations thus having pleiotropic effects on blood glucose homeostasis (48,39). Recent studies have shown that metformin treatment leads to changes in gut microbiota and relative abundance of microbial metabolites (49,50). Cumulative evidence from those reports confirms that hypoglycemic effects of metformin were associated with AMPK activation and microbial metabolites involved in energy metabolism, gluconeogenesis and branched-chain amino acid metabolism.…”

Section: Metformin Pharmacodynamicsmentioning

confidence: 99%

A Review of the Impact of Pharmacogenetics and Metabolomics on the Efficacy of Metformin in Type 2 Diabetes

Damanhouri¹,

Alkreathy²,

Alharbi³

et al. 2023

Int. J. Med. Sci.

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Metformin is the most often prescribed drug for people with type 2 diabetes (T2D). More than 120 million patients with T2D use metformin worldwide. However, monotherapy fails to achieve glycemic control in a third of the treated patients. Genetics contribute to some of the inter-individual variations in glycemic response to metformin. Numerous pharmacogenetic studies have demonstrated that variations in genes related to pharmacokinetics and pharmacodynamics of metformin's encoding transporters are mainly associated with metformin response. The goal of this review is to evaluate the current state of metformin pharmacogenetics and metabolomics research, discuss the clinical and scientific issues that need to be resolved in order to increase our knowledge of patient response variability to metformin, and how to improve patient outcomes. Metformin's hydrophilic nature and absorption as well as its action mechanism and effectiveness on T2D initiation are discussed. The impacts of variations associated with various genes are analysed to identify and evaluate the effect of genetic polymorphisms on the therapeutic activity of metformin. The metabolic pattern of T2D and metformin is also indicated. This is to emphasise that studies of pharmacogenetics and metabolomics could expand our knowledge of metformin response in T2D.

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Section: Metformin Pharmacodynamicsmentioning

confidence: 99%

A Review of the Impact of Pharmacogenetics and Metabolomics on the Efficacy of Metformin in Type 2 Diabetes

Damanhouri¹,

Alkreathy²,

Alharbi³

et al. 2023

Int. J. Med. Sci.

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“…The neuroendocrine hormone PPY affects food intake and energy balance. Reduced GLP-1 secretion in T2DM results in decreased insulin levels and poor glucose and energy metabolism[ 9 ](Figure 1 ). In dysbacteriosis, low SCFA production and impaired activation of SCFA receptors are seen in the intestinal tract.…”

Section: Intestinal Flora Mechanisms In the Formation And Development...mentioning

confidence: 99%

“…As a result of the decreased TGR5 stimulation with the changing BA content, the released GLP-1 decreases. This causes insulin resistance and increased glucose[ 9 ]. Bacterial diseases result in decreased bile acid activation and diminished FXR activation, which contribute in a variety of ways to the development of T2DM.…”

Section: Intestinal Flora Mechanisms In the Formation And Development...mentioning

confidence: 99%

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Role of natural products and intestinal flora on type 2 diabetes mellitus treatment

Aydin¹,

Aydın²,

Barun³

2023

World J Clin Cases

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Diabetes mellitus (DM) is a complicated, globally expanding disease that is influenced by hereditary and environmental variables. Changes in modern society's food choices, physical inactivity, and obesity are significant factors in the development of type 2 DM (T2DM). The association between changes in intestinal flora and numerous disorders, including obesity, diabetes, and cardiovascular diseases, has been studied in recent years. The purpose of this review is to analyze the mechanisms underlying the alteration of the diabetic patients' intestinal flora, as well as their therapeutic choices. Also included is a summary of the anti-diabetic benefits of natural compounds demonstrated by studies. The short-chain fatty acids theory, the bile acid theory, and the endotoxin theory are all potential methods by which intestinal flora contributes to the establishment and progression of T2DM. Due to an intestinal flora imbalance, abnormalities in short-chain fatty acids and secondary bile acids have been found in diabetic patients. Additionally, metabolic endotoxemia with altering flora induces a systemic inflammatory response by stimulating the immune system via bacterial translocation. The agenda for diabetes treatment includes the use of short-chain fatty acids, probiotics, prebiotics in the diet, fecal bacteria transplantation, and antibiotics. Animal studies have proven the antidiabetic benefits of numerous bioactive substances, including Flavonoids, Alkaloids, Saponin, and Allicin. However, further research is required to contribute to the treatment of diabetes.

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“…Although patients with T2DM have not been shown to harbor specific gut bacteria assigned as a disease enterotype, T2DM is known to alter gut microbes. Several studies have shown bacterial changes at the genus level, with a predominance of Bifidobacterium, Bacteroides, Roseburia, Faecalibacterium, and Akkermansia being inversely correlated with T2DM [ 10 , 18 , 19 ]. The association, however, remains controversial.…”

Section: Introductionmentioning

confidence: 99%

Fecal Bacterial Community and Metagenome Function in Asians with Type 2 Diabetes, According to Enterotypes

Park

2022

Biomedicines

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The role of gut microbes has been suggested in type 2 diabetes (T2DM) risk. However, their results remain controversial. We hypothesized that Asians with T2DM had different fecal bacterial compositions, co-abundance networks, and metagenome functions compared to healthy individuals, according to enterotypes. This hypothesis was examined using the combined gut microbiota data from human fecal samples from previous studies. The human fecal bacterial FASTA/Q files from 36 different T2DM studies in Asians were combined (healthy, n = 3378; T2DM, n = 551), and operational taxonomic units (OTUs) and their counts were obtained using qiime2 tools. In the machine learning approaches, fecal bacteria rich in T2DM were found. They were separated into two enterotypes, Lachnospiraceae (ET-L) and Prevotellaceae (ET-P). The Shannon and Chao1 indices, representing α-diversity, were significantly lower in the T2DM group compared to the healthy group in ET-L (p < 0.05) but not in ET-P. In the Shapley additive explanations analysis of ET-L, Escherichia fergusonii, Collinsella aerofaciens, Streptococcus vestibularis, and Bifidobacterium longum were higher (p < 0.001), while Phocaeicola vulgatus, Bacteroides uniformis, and Faecalibacterium prausnitzii were lower in the T2DM group than in the healthy group (p < 0.00005). In ET-P, Escherichia fergusonii, Megasphaera elsdenii, and Oscillibacter valericigenes were higher, and Bacteroides koreensis and Faecalibacterium prausnitzii were lower in the T2DM group than in the healthy group. In ET-L and ET-P, bacteria in the healthy and T2DM groups positively interacted with each other within each group (p < 0.0001) but negatively interacted between the T2DM and healthy groups in the network analysis (p < 0.0001). In the metagenome functions of the fecal bacteria, the gluconeogenesis, glycolysis, and amino acid metabolism pathways were higher, whereas insulin signaling and adenosine 5′ monophosphate-activated protein kinase (AMPK) signaling pathways were lower in the T2DM group than in the healthy group for both enterotypes (p < 0.00005). In conclusion, Asians with T2DM exhibited gut dysbiosis, potentially linked to intestinal permeability and the enteric vagus nervous system.

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Effects of Oral Glucose-Lowering Agents on Gut Microbiota and Microbial Metabolites

Cited by 11 publications

References 175 publications

A Review of the Impact of Pharmacogenetics and Metabolomics on the Efficacy of Metformin in Type 2 Diabetes

A Review of the Impact of Pharmacogenetics and Metabolomics on the Efficacy of Metformin in Type 2 Diabetes

Role of natural products and intestinal flora on type 2 diabetes mellitus treatment

Fecal Bacterial Community and Metagenome Function in Asians with Type 2 Diabetes, According to Enterotypes

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