Microbiome & Chronic Diseases

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Disease ⇒ Diabetes Type 2 {40000105}

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Diabetes Type 2
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Other Terms:
T2D, adult-onset diabetes


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- The microbiome literature on T2D appears chaotic and concerns have been raised about variability of the results. Different taxa are reported to be associated with T2D in different studies. Furthermore, a recent large study observed that different microbes were found associated with the same metabolic outcomes in different geographical areas.

- Enterobacter cloacae B29 induced obesity and insulin resistance in germ-free mice. (3)

- PPI use is associated with reduced diversity of gut microbiome and consistent changes in the microbiota phenotype. (5)
- GIPR postbiotic agonist/antagonist may caus/prevent DM

References Notes

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Shared Reference Notes

  • [1.39
    - Diabetes taking metformin had higher relative abundance of Akkermansia muciniphila, a microbiota known for mucin degradation, and several gut microbiota known for production of SCFAs, including Butyrivibrio, Bifidobacterium bifidum, Megasphaera, and an operational taxonomic unit of Prevotella.
  • [1.40
    - Duodenal hypercontractility observed during T2D leads to the genesis of aberrant signalling from the afferent nerves to the hypothalamus, contributing to systemic insulin resistance
    - Enteric NO has the capacity to decrease duodenal contractions and restore the gut-brain axis, subsequently improving insulin sensitivity
    - Prebiotic treatment (oligofructose) decreases duodenal hypercontractility by modulating ENS activity and an increase in the levels of an intestinal lipid, 12-hydroxyeicosatetraenoic acid (12-HETE).
    - The mechanism of prebiotic action implies the presence of an enkephalin/mu-opioid receptor and proliferator-activated receptor γ signalling and a bioactive lipid, 12S-hydroxyeicosatetraenoic acid.
  • [1.34
    - Synbiotic yogurt-fed mice demonstrated lower fasting blood glucose (FBG) levels.
    - The blood glucose rise during the meal tolerance test (MTT) is lower in the synbiotic yogurt-fed mice
    - Insulin sensitivit in not impacted by Synbiotic yogurt-fed in mice.
    - the abundances of fecal Proteobacteria and Enterobacteriacae correlate positively with FBG levels which increase the progression of diabetes in mice.
  • [1.41
    - Agonism of GIP receptor (GIPR) have glycemic effect.
  • [1.42
    - There is a significant correlation between gut microbiota dysbiosis and an elevated level of interleukin 6 (IL-6) in plasma samples of patients with type 2 diabetes (T2D)
  • [1.43
    - The feeding of the synbiotic yogurt significantly reduced the development of hyperglycemia (diabetes) in response to high-fat diet feeding and streptozotocin compared to milk-fed controls.
  • [1.44
    - The commonly used diabetes treatment Metformin increase Akkermansia spp. abundance, and to significantly improve glucose metabolism in high-fat diet fed mice while also increasing the number of mucin-producing goblet cells.
  • [1.45
    - Gut-targeted delayed-release NA but not NAM produced a significant increase in the abundance of Bacteroidetes.
    - In the absence of systemic side effects, these favorable microbiome changes induced by microencapsulated delayed-release NA were associated with an improvement of biomarkers for systemic insulin sensitivity and metabolic inflammation.
  • [1.46
    - Genera of Bifidobacterium, Bacteroides, Faecalibacterium, Akkermansia and Roseburia were negatively associated with T2D, while the genera of Ruminococcus, Fusobacterium, and Blautia were positively associated with T2D.
  • - Bifidobacterium appears to be the most consistently supported by the literature genus containing microbes potentially protective against T2D
  • - there is a negative association between specific species such as B. adolescentis, B. bifidum, B. pseudocatenulatum, B. longum, B. dentium and disease in patients treated with metformin or after undergoing gastric bypass surgery
  • [1.47
    - In a mouse model oral administration of Akkermansia activated toll-like receptor 2, increased the expression of epithelial tight-junction proteins, and reversed high-fat diet-induced insulin resistance
    - Akkermansia was the only genus that was underrepresented in patients with elevated HbA1c
  • - Anaerostipes is positively associated with type 2 diabetes. Similarly, in studies of type 1 diabetes and gestational diabetes, Parabacteroides was elevated compared to healthy controls.
  • - Parabacteroides is positively associated with diabetes.
  • [1.48
    - High fiber diet > Prevotella copri > improve glucose and insulin tolerance.
  • [1.37
    - Four G-protein coupled receptors (GPCRs) for SCFAs have been identified: GPR41 (free fatty acid receptor 3), GPR43 (free fatty acid receptor 2), GPR109a, and olfactory receptor 78.
    - Of the 4 receptors, the 2 most directly implicated in T2DM are GPR41 and GPR43.
    - GPR41 recognizes all 3 SCFAs but is activated 10-fold less by acetate and is reported to be expressed in adipose tissue, the gut by intestinal L-cells, the nervous system, and the kidney.
    - GPR41 resulted in increased gut motility via reduced peptide YY (PYY) secretion, which resulted in decreased intestinal absorption of nutrients, implicating a role in food consumption.
    - GPR41 activation stimulate energy expenditure, thereby having a protective effect against T2DM onset.
    In the kidney, GPR41 seems to play a role in decreasing blood pressure, which could play a protective role againstT2DM-mediated kidney damage in later disease stages.
    - Treatment with SCFAs in both rodent models and humans improves T2DM phenotypes
  • - In diabetic mice, the administration of a synthetic FXR agonist markedly reduced plasma glucose, triglycerides, free fatty acids, and cholesterol as well as hepatic steatosis.
    - Conversely, intestine-specific knockout of FXR in mice was shown to reduce insulin resistance and hepatic triglyceride accumulation
  • - TGR5, unlike the nuclear receptors discussed above, is a GPCR, expressed by digestive, immune, and adipose tissues where it is preferentially activated by LCA and DCA.
    - In the gut, TGR5 activation leads to secretion of GLP-1 and PYY, thereby having beneficial effects on insulin secretion and satiety.
    - TGR5 knockout in macrophages and myeloid-lineage cells was found to exacerbate adipose tissue inflammation and insulin resistance, suggesting a protective role in T2DM pathogenesis
  • - Among obese individuals with at least 1 comorbidity the production of indole, IPA, indole 3-acetic acid, and indole 3-carboxaldehyde is decreased versus lean individuals, suggesting that a change in meta-organismal tryptophan metabolism may occur prior to T2DM onset and thus may contribute to its development.
  • - The microbial product of histidine metabolism, imidazole propionate (ImP), was recently shown to be directly involved in insulin resistance.
    - Exogenous ImP showed worsened glucose tolerance, increased gluconeogenic enzyme expression, increased S6 kinase phosphorylation, and impaired insulin signaling in multiple tissues on a normal chow diet. In vitro ImP also impaired insulin-stimulated phosphorylation of protein kinase B.
    - ImP activates mTORC1.
  • - TMA and subsequent conversion to TMAO by host FMO3 is related to T2DM pathogenesis and comorbidities.
    - Mice with selective hepatic insulin resistance have elevated levels of circulating TMAO.
    - Dietary supplementation with TMAO can exacerbate glucose intolerance in high-fat–fed mice.
    - High concentrations TMAO directly binds to and activates PERK, a key effector of the unfolded protein response in the liver, promoting hyperglycemia and metabolic dysfunction
  • [1.49
    - Lachnospira contribute to diabetes in obese mice and is enriched in obese children
  • [1.50
    - Individuals with T2D have lower gut microbiome alpha diversity compared with healthy controls and they also show impaired SCFA butyrate production,12 modifications in incretin secretion, reducing intestinal permeability leading to metabolic endotoxemia (increased LPS in blood) that is linked to increasing metabolic inflammation and insulin resistance induced by high-fat diet.
  • [1.59
    - Lactobacillus > positively correlated with fasting glucose and HbA1c levels > increased insulin resistance.
  • - Clostridium > negative correlation with with fasting glucose and HbA1c levels > decreased insulin resistance.
  • [1.61
    - TIIDM > low levels of Roseburia inulinivorans, Eubacterium eligens , and Bacteroides vulgatus,
    - All these bacteria > increase following the “good” diet and > decrease following the “bad” diet.
  • - Low levels of Anaerostipes > improved glucose tolerance and reduced plasma triglyceride levels in mice
  • [1.62
    - Prob+BBR superior to BBR or Prob alone in improving postprandial total cholesterol (pTC) and low-density lipoprotein cholesterol (pLDLc) levels with decrement of multiple species of postprandial lipidomic metabolites after 3 months follow-up.
    - This effect was linked to the changes of fecal Bifidobacterium breve level responding to BBR alone or Prob+BBR treatment.
    - Four fadD genes encoding long-chain acyl-CoA synthetase > identified in the genome of this B. breve strain, and transcriptionally activated by BBR.
    - The activation of fadD by BBR could enhance FFA import and mobilization in B. breve and diliminish the intraluminal lipids for absorption to mediate the effect of Prob+BBR on PL.
  • [1.63
    - In patients with pre-diabetes and hypovitaminosis D : high dose vitamin D > improves insulin sensitivity and decreases risk of progression toward diabetes.
  • [1.64
    - gut microbiota, especially Faecalibacterium, Predict postprandial glucose response (PPGR) after eating potatoes.
  • [1.65
    - Probiotic supplements do not induce clinically significant reductions in HbA1c levels, but lead to marginally clinically significant reductions in fasting glucose and fasting insulin levels in patients with type 2 diabetes.
    - Compared with single-strain and low-dose probiotics, multi-strain and high-dose probiotics have a greater beneficial effect on glycemic homeostasis.
  • [1.30
    - Black women, regardless of insulin sensitivity > greater relative abundance of the phylum Actinobacteria, compared to White women.
    - Black women with insulin resistance > four fold higher Verrucomicrobia abundance than White women.
  • [1.66
    - spermine, acyl-alkyl sphingomyelin, hydroxy sphingomyelin, and sphingomyelin were associated with incident type 2 diabetes in obese individuals after the adjustment for risk factors and correction of multiple comparisons by Bonferroni method.
  • [1.67
    - These four species were Clostridium citroniae, C. bolteae, Tyzzerella nexilis, and Ruminococcus gnavus.
  • [1.68
    - yogurt intake impacts the hepatic metabolome, notably maintaining the levels of branched chain hydroxy acids (BCHA) which correlate with improved metabolic parameters
  • [1.69
    - SCFAs-induced improvements in adipose tissue metabolism can prevent insulin resistance, while succinate improves the host insulin sensitivity while preventing obesity.
  • - p-cresol was shown to have the potential to induce diabetes, with mice given p-cresol sulfate for four consecutive weeks showing an insulin-resistant phenotype.
  • - dimethylglycine, imidazole propionate, tryptophan, kynurenine and indolelactate associated with increased risk of T2D
  • - 1-linoleoylglycerophosphocholine and indole-3-propionic acid (indolepropionic) are potentially to significantly reducing T2D risk.
  • - butyrate has also been shown to increase diverse circulating glucose-regulating hormones by promoting intestinal expression of GLP-1, ultimately lowering blood glucose levels.
  • [1.70
    - Amylase levels were decreased in the pancreas by the HFD. Interestingly, however, these changes at the level of the pancreas were totally reversed by vancomycin treatment, while metronidazole treatment further decreased the amylase levels.
    - Elastase, on the other hand, showed a trend of increase in the pancreas of the HFD and metronidazole-treated groups and significantly increased with vancomycin treatment in the pancreas.
    - Lipase in pancreatic samples was also significantly increased with HFD feeding but normalized by both antibiotics
  • - HFD caused a decrease in circulating GLP-1 levels, and this was reversed with vancomycin treatment
  • [1.71
    - In healthy human subjects Akkermansia muciniphila was associated to low body weight, low body fat proportion, reduced adipose tissue inflammation and reduced insulin resistance.
  • [1.26
    - Germ-free mice gavaged either with Prevotella copri or “responder” human-derived microbiomes containing P. copri showed improvements in glucose tolerance when fed standard chow diets, which was mechanistically associated with increased hepatic glycogen storage.
  • [1.14
    - LPS acts as a strong stimulant for the release of cytokines, which are key inducers of insulin resistance.
    - The bacterial lipopolysaccharide (LPS) from Escherichia coli has been shown to exhibit major effects on insulin sensitivity
  • - Elevated IL-6 and CRP levels associated with Periodontitis, as significant risk factors for insulin resistance and diabetes mellitus
  • - Diabetes > significant depletion of Coriobacteriaceae, Veillonellaceae, Streptococcaceae, and enrichment of Burkholderiaceae and Burkholderiales families in the gut.
  • [1.72
    - Akkermansia muciniphila is a mucin degraders, an important role in the preservation of the integrity of the gut mucus layer, thus
    limiting the risk of systemic inflammation.
    - Dietary polyphenols such as anthocyanins (ACNs) and proanthocyanidins (PACs) protect against metabolic syndrome.
    - Supplementation of high-fat diets with ACNs or PACs has been shown to suppress the expression of genes involved in fatty acid and triacylglycerol synthesis, the regulation of lipogenesis and cholesterol biosynthesis, and the assembly of very low density
    - ACNs and PACs have also been argued to stem the development of insulin resistance by increasing insulin signaling, glycogen accumulation and adiponectin secretion in the presence of free fatty acids.
    A. muciniphila abundance has been linked to reduced weight gain, adiposity, insulin resistance, and/or inflammatory markers in many contexts, including during pregnancy.
  • [1.73
    - Faecalibacterium prausnitzii, an indicator of inflammation, shows a decreased abundance in diabetes and obese persons.

Common References