Gut Microbiota: An Important Player in Type 2 Diabetes Mellitus

Zhou, Zhiyuan; Sun, Bao; Yu, Dongsheng; Zhu, Chunsheng

doi:10.3389/fcimb.2022.834485

Cited by 130 publications

(102 citation statements)

References 160 publications

(179 reference statements)

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“…GM, which consisted of 500–1000 different species, is recognized as a complex “organ” maintaining host health [ 31 ]. However, more and more studies have proved that gut dysbiosis plays an important role in T2DM and inflammatory reactions [ 32 ]. Generally, GM is divided into commensal bacteria, beneficial bacteria, and conditionally pathogenic bacteria (also mentioned as pathobiont), which participate in regulating the intestinal barrier, intestinal peristalsis, synthesis of vitamins, and reabsorption of substances [ 33 ].…”

Section: Discussionmentioning

confidence: 99%

Fufang Fanshiliu Decoction Revealed the Antidiabetic Effect through Modulating Inflammatory Response and Gut Microbiota Composition

Huang

Chen³

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Background. Diabetes mellitus brings serious threats and financial burdens to human beings worldwide. Fufang Fanshiliu decoction (FFSLD), a traditional Chinese medicine formula showing great antidiabetic effects, has been used in clinics for many years. Objective. This study aims to explore the underlying therapeutic mechanisms of FFSLD in Type II diabetes mellitus (T2DM). Methods. Sprague–Dawley rats induced by high-fat diet feeding combined with streptozotocin injection were used to establish the T2DM model. All rats were randomly divided into 6 groups: control, model, metformin, high dosage, middle dosage, and low dosage of FFSLD. After 4 weeks of treatment, serum, intestinal mucosa, and fecal samples were collected for further analysis. ELISA was used to detect the diabetic-related serum indicators and proinflammation cytokines. Gene or protein expressions of mitogen-activated protein kinase (MAPK), interleukin 1 beta (IL-1β), transforming growth factor-beta (TGF-β), and tumor necrosis factor-alpha (TNF-α) in intestinal mucosa were analyzed by quantitative real-time polymerase chain reaction (RT-PCR) or western blot. 16s rRNA gene sequencing was used to detect the changes of gut microbiome in these groups. Intestinal gut microbiota (GM) composition was further analyzed according to the sequencing libraries. Results. FFSLD effectively recovered the diabetic-related biochemical indexes by reducing fasting blood glucose (FBG), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), insulin, and increasing high-density lipoprotein cholesterol (HDL-C). Furthermore, FFSLD significantly ameliorated the abnormal levels of proinflammation cytokines including IL-1β, IL-6, TNF-α, and TGF-β. In addition, the GM compositions of rats in control, model, and FFSLD treated groups were different. FFSLD significantly increased the relative abundance of Lactobacillus, Akkermansia, and Proteus, and reduced the relative abundance of Alistipes, Desulfovibrio, and Helicobacter. Moreover, these changed bacteria were closely related to the diabetic-related serum indicators and proinflammatory cytokines. Conclusion. These results suggest that FFSLD alleviates diabetic symptoms in T2DM rats through regulating GM composition and inhibiting inflammatory response, which clarify the therapeutic mechanism of FFSLD on T2DM and provide a theoretical basis for its further clinical application.

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Section: Discussionmentioning

confidence: 99%

Fufang Fanshiliu Decoction Revealed the Antidiabetic Effect through Modulating Inflammatory Response and Gut Microbiota Composition

Huang

Chen³

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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“…Type 2 diabetes mellitus (T2DM) is a chronic progressive metabolic disease characterized by pancreatic β-cell dysfunction as well as insulin resistance ( 1 ). According to statistics, approximately 1 in 11 adults worldwide has diabetes, 90% of whom have T2DM ( 2 ).…”

Section: Introductionmentioning

confidence: 99%

Optimal dose of tirzepatide for type 2 diabetes mellitus: A meta-analysis and trial sequential analysis

Yin

et al. 2022

Front. Cardiovasc. Med.

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ObjectiveThe purpose of this study is to evaluate the optimal dose of tirzepatide (TZP) for the treatment of type 2 diabetes mellitus (T2DM) by meta-analysis and trial sequential analysis (TSA).MethodsClinical trials of TZP for T2DM were obtained by searching 8 databases with a time limit from database creation to May 2022. Mean differences (MD) and 95% confidence intervals (95%CI) were used for continuous variables, and relative risk (RR) and 95%CI were used for dichotomous variables.ResultsCompared with TZP 5 mg, meta-analysis showed that TZP 10 mg significantly reduced glycosylated hemoglobin type A1c (HbA1c) (MD −0.24, 95%CI −0.31~-0.17, P < 0.00001), fasting serum glucose (FSG) (MD −5.82, 95%CI −8.35~-3.28, P < 0.00001) and weight (MD −2.47, 95%CI −2.95~-1.98, P < 0.00001), and TZP 15 mg significantly reduced HbA1c (MD −0.37, 95%CI −0.44~-0.29, P < 0.00001), FSG (MD −8.52, 95%CI −11.07~-5.98, P < 0.00001) and weight (MD −4.63, 95%CI −5.45~-3.81, P < 0.00001). Compared with TZP 10 mg, TZP 15 mg dramatically reduced HbA1c (MD −0.12, 95%CI −0.19~-0.05, P = 0.001), FSG (MD −2.73, 95%CI −5.29~-0.17, P = 0.04) and weight (MD −2.18, 95%CI −2.67~-1.70, P < 0.00001). The TSA indicated that the benefits observed in the current information set were conclusive, except for the FSG of “TZP 15 mg vs. TZP 10 mg”. In terms of safety endpoints, meta-analysis revealed that there was no significant difference in the serious adverse events (AEs), major adverse cardiovascular events-4 (MACE-4), cardiovascular death, hypertension, cancer and hypoglycemic of the three dose groups of TZP. Compared with TZP 5 mg, TZP 10 mg increased total adverse events (RR 1.06, 95%CI 1.01~1.11, P = 0.03) and gastrointestinal (GI) AEs (RR 1.17, 95%CI 1.03~1.33, P = 0.02), and TZP 15 mg increased total AEs (RR 1.10, 95%CI 1.05~1.15, P = 0.0001). There were no significant differences in total AEs and GI AEs for TZP 15 mg compared to TZP 10 mg. The TSA demonstrated that the total AEs of “TZP 15 mg vs. TZP 5 mg” were conclusive.ConclusionsTZP 15 mg >TZP 10 mg > TZP 5 mg in terms of lowering glycemia and reducing weight. TZP 5 mg > TZP 10 mg = TZP 15 mg in terms of safety. On this basis, we recommend TZP 5 mg as the first-choice dose for patients with T2DM to minimize AEs while reducing glycemia and weight. If patients cannot effectively control their glycemia after taking TZP 5 mg, it is recommended to take TZP 15 mg directly to achieve the best effect of glycemic reduction. However, most of the included studies have the background of basic medication, the independent efficacy and safety of different doses of TZP still need to be tested.Systematic review registrationUnique Identifier: CRD42022341966.

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“…Regarding its effects on gut health, butyrate maintains the integrity of intestinal epithelial barrier by promoting the assembly of ZO-1 and occludin, impeding the LPS translocation, inhibiting the release of inflammatory factors from macrophage, and reducing the inflammatory reactions. − Other SCFAs like acetate and propionate are also beneficial due to their positive modulating effects on insulin sensitivity and reduction of plasma FFAs . Besides, propionate can also maintain the glucose and energy homeostasis and is beneficial for weight loss . Further, it affects the glucose metabolism via decreasing plasma fatty acids and modulating insulin sensitivity …”

Section: Scfas and Gut Microbiota Dysbiosis In Dmmentioning

confidence: 99%

“…150 Besides, propionate can also maintain the glucose and energy homeostasis and is beneficial for weight loss. 151 Further, it affects the glucose metabolism via decreasing plasma fatty acids 141 and modulating insulin sensitivity. 152 The benefits of SCFAs are proposed to be mediated by the following mechanisms.…”

Section: ■ Scfas and Gut Microbiota Dysbiosis In Dmmentioning

confidence: 99%

Metabolites of Gut Microbiota and Possible Implication in Development of Diabetes Mellitus

Guo

Pan

Hui

et al. 2022

J. Agric. Food Chem.

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Diabetes mellitus is characterized by having a disorder of glucose metabolism. The types of diabetes mellitus include type 1 diabetes mellitus, type 2 diabetes mellitus, gestational diabetes mellitus, and other specific types of diabetes mellitus. Many risk factors contribute to diabetes mellitus mainly including genetics, environment, obesity, and diet. In the recent years, gut microbiota has been shown to be linked to the development of diabetes. It has been reported that the gut microbiota composition of diabetic patients is different from that of healthy people. Although the mechanism behind the abnormality remains to be explored, most hypotheses focus on the inflammation response and leaky gut in relation to the changes in production of endotoxins and metabolites derived from the intestinal flora. Consequently, the above-mentioned abnormalities trigger a series of metabolic changes, gradually leading to development of hyperglycemia, insulin resistance, and diabetes. This review is (i) to summarize the differences in gut microbiota between diabetic patients and healthy people, (ii) to discuss the underlying mechanism(s) by which how lipopolysaccharide, diet, and metabolites of the gut microbiota affect diabetes, and (iii) to provide a new insight in the prevention and treatment of diabetes.

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Gut Microbiota: An Important Player in Type 2 Diabetes Mellitus

Cited by 130 publications

References 160 publications

Fufang Fanshiliu Decoction Revealed the Antidiabetic Effect through Modulating Inflammatory Response and Gut Microbiota Composition

Fufang Fanshiliu Decoction Revealed the Antidiabetic Effect through Modulating Inflammatory Response and Gut Microbiota Composition

Optimal dose of tirzepatide for type 2 diabetes mellitus: A meta-analysis and trial sequential analysis

Metabolites of Gut Microbiota and Possible Implication in Development of Diabetes Mellitus

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