Gut microbiota induces DNA methylation via SCFAs predisposing obesity-prone individuals to diabetes

Guo, Wenqian; Zhang, Zengliang; Li, Lingru; Liang, Xue; Wu, Yuqi; Wang, Xiaolu; Ma, Han; Cheng, Jinjun; Zhang, Anqi; Tang, Ping; Wang, Chong‐Zhi; Wan, Jianwei; Yao, Haiqiang; Yuan, Chun‐Su

doi:10.1016/j.phrs.2022.106355

Cited by 76 publications

(22 citation statements)

References 55 publications

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“…Compared to other SCFAs, propionate demonstrated the greatest difference between obese and lean participants, with propionate levels significantly higher in obese participants [29]. Meanwhile, propionate was found to be the most symbolic SCFA of persons who are prone to obesity by the variable importance in projection (VIP) score [30]. As reported by Emanuel et al [31], propionate may affect lipoprotein lipase inhibitors, such as angiopoietin-like 4 (ANGPTL4), increasing free fatty acid uptake.…”

Section: Discussionmentioning

confidence: 85%

Gut Microbiota-Derived Short Chain Fatty Acids Are Associated with Clinical Pregnancy Outcome in Women Undergoing IVF/ICSI-ET: A Retrospective Study

et al. 2023

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Gut microbiota and its metabolites are related to the female reproductive system. Animal experiments have demonstrated the relationship between gut microbiota-derived short chain fatty acids (SCFAs) and embryo quality. However, few studies have linked SCFAs to clinical pregnancy outcomes in humans. This retrospective cross-sectional study recruited 147 patients undergoing in vitro fertilization or intracytoplasmic sperm injection and embryo transfer (IVF/ICSI-ET) (70 with no pregnancies and 77 with clinical pregnancies). The association between SCFAs levels and clinical pregnancy outcomes was evaluated using univariate and multivariate logistic regression analyses. The association between SCFAs and metabolic parameters was analyzed using a linear regression model. Receiver operating characteristic (ROC) curve analysis was used for assessing the efficiency of SCFAs to evaluate the clinical pregnancy outcomes. Fecal propionate levels were significantly higher in the no pregnancy group than in the clinical pregnancy group (p < 0.01). Fecal acetate and butyrate levels were not significantly different between females with and without clinical pregnancies (p > 0.05). There were positive relationships between fecal propionate levels and fasting serum insulin (FSI) (r = 0.245, p = 0.003), Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) (r = 0.276, p = 0.001), and triglycerides (TG) (r = 0.254, p = 0.002). Multivariate analyses determined that fecal propionate (OR, 1.103; 95% CI, 1.045–1.164; p < 0.001) was an independent risk factor for no pregnancies. The area under the ROC curve (AUC) of fecal propionate was 0.702 (p < 0.001), with a sensitivity of 57.1% and a specificity of 79.2%. High fecal propionate concentration has a negative association on clinical pregnancy outcomes and is positively correlated with FSI, TG, and HOMA-IR.

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Section: Discussionmentioning

confidence: 85%

Gut Microbiota-Derived Short Chain Fatty Acids Are Associated with Clinical Pregnancy Outcome in Women Undergoing IVF/ICSI-ET: A Retrospective Study

et al. 2023

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“…In type-I DM, dysfunctional pancreatic cells prohibit the production of sufficient hormone, but in type-II DM, [6] insulin resistance or lack of insulin activity in the body is to blame. [7,8] By blocking the breakdown of polysaccharides into their basic monomers, α-glucosidase inhibition lowers blood sugar levels.. [9,10] The local action of the α-glucosidase inhibitors in the human intestine distinguishes them from other hypoglycemic medications that control specific metabolic processes. [11,12] Meanwhile, these inhibitors' therapeutic applications are accompanied by unwanted side effects such flatulence, [13] diarrhea, [14] and abdominal pain.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of Flurbiprofen Based Amide Derivatives as Potential Leads for Diabetic Management: In Vitro α‐glucosidase Inhibition, Molecular Docking and DFT Simulation Approach

Alam,

Zainab,

Elhenawy

et al. 2024

ChemistrySelect

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This research is based on the synthesis, characterization and in vitro α‐glucosidase inhibitory activity of fourteen amides (2 a–2 n) of flurbiprofen drug. Seven compounds in the series displayed potent inhibitory activity having IC50 values (IC50=5.67±0.89 μM) to (IC50=17.87±2.39 μM) in comparison with acarbose standard (IC50=875.75±1.24 μM). The FMO of 2 a–2 n molecules was quantified by the DFT assay. The promising value for energygap explained the higher poteny agannist α‐glucosidase. MEP provides the insights into the distribution of electrostatic potential on the molecular surface of 2 a–2 n, showing that C=O group has the highest negative potential. The AIM investigation revealed minimal hydrogen bond energy and non‐covalent interactions. This suggests that these molecules may have limited hydrogen bonding and non‐covalent interactions, which could be relevant to their chemical behavior. Molecular docking and (MEP) showed the C=O group, with its high negative potential, is a key in recognizing the catalytic non‐polar regions of enzymes, such as TYR72, GLU277, and ARG442. Similarly, the hydrophobic regions of investigated compounds play a significant role in identifying essential amino acids like ASP352 and ARG442, which are vital for the ligand's proper orientation and subsequent biological activity.

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“…It also regulates lipid metabolism and inhibits lipolysis in adipose tissue ( 48 ). A recent study also shows that SCFAs may contribute to the development of diabetes through DNA methylation ( 49 ).…”

Section: Diabetes and Gut Microbial Metabolitesmentioning

confidence: 99%

Targeting the gut microbiota and its metabolites for type 2 diabetes mellitus

Yang

Fan

et al. 2023

Front. Endocrinol.

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Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by hyperglycemia and insulin resistance. The incidence of T2DM is increasing globally, and a growing body of evidence suggests that gut microbiota dysbiosis may contribute to the development of this disease. Gut microbiota-derived metabolites, including bile acids, lipopolysaccharide, trimethylamine-N-oxide, tryptophan and indole derivatives, and short-chain fatty acids, have been shown to be involved in the pathogenesis of T2DM, playing a key role in the host-microbe crosstalk. This review aims to summarize the molecular links between gut microbiota-derived metabolites and the pathogenesis of T2DM. Additionally, we review the potential therapy and treatments for T2DM using probiotics, prebiotics, fecal microbiota transplantation and other methods to modulate gut microbiota and its metabolites. Clinical trials investigating the role of gut microbiota and its metabolites have been critically discussed. This review highlights that targeting the gut microbiota and its metabolites could be a potential therapeutic strategy for the prevention and treatment of T2DM.

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Gut microbiota induces DNA methylation via SCFAs predisposing obesity-prone individuals to diabetes

Cited by 76 publications

References 55 publications

Gut Microbiota-Derived Short Chain Fatty Acids Are Associated with Clinical Pregnancy Outcome in Women Undergoing IVF/ICSI-ET: A Retrospective Study

Gut Microbiota-Derived Short Chain Fatty Acids Are Associated with Clinical Pregnancy Outcome in Women Undergoing IVF/ICSI-ET: A Retrospective Study

Synthesis of Flurbiprofen Based Amide Derivatives as Potential Leads for Diabetic Management: In Vitro α‐glucosidase Inhibition, Molecular Docking and DFT Simulation Approach

Targeting the gut microbiota and its metabolites for type 2 diabetes mellitus

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