Disease ⇒ Diabetes Type 2 {40000105} Record Keys Type:Disease Parent:[ ] Definition:Diabetes Type 2 Details Initialisation date:2020-09-06 Other Terms:T2D, adult-onset diabetes LinksWickipediaMerck Manual Meta Information MedDra ID:10067585 MedDra Level:pt ICD:[ ] Category:[ ] Zone:[ ] Mechanism:[ ] Notes: - 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 Shared Reference Notes [1.1] - 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. [1.2] - 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. [1.3] - 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. [1.4] - Agonism of GIP receptor (GIPR) have glycemic effect. [1.5] - 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) [1.6] - 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. [1.7] - 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. [1.8] [#Niacin] [#Microencapsulated delayed-release Nicotinic Acid] - 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. [1.9] - 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 - 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. [1.11] [#High fibre diet] - High fiber diet > #Prevotella copri > improve glucose and insulin tolerance. [1.12] [#Bile Acids] - 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 [#Bile Acids] - 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 - 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. [#Indole-3-acetic acid] - 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. [#Short Chain Fatty Acid] - 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 - 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 [1.13] - #Lachnospira contribute to diabetes in obese mice and is enriched in obese children [1.14] - 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. [1.15] [1.16] [1.17] [1.18] [1.19] [#Butyrate] [1.21] [1.22] [1.23] - #Clostridium > negative correlation with with fasting glucose and HbA1c levels > decreased insulin resistance. - #Lactobacillus > positively correlated with fasting glucose and HbA1c levels > increased insulin resistance. [1.24] [1.25] - Low levels of #Anaerostipes > improved glucose tolerance and reduced plasma triglyceride levels in mice - 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. [1.26] [#CVD, #Dyslipidemia, #Postprandial lipidemia] [#Berberine] [#Probiotic] - 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. [1.27] - In patients with pre-diabetes and hypovitaminosis D : high dose #Vitamin D > improves insulin sensitivity and decreases risk of progression toward diabetes. [1.28] [#Obesity] [#Gender, #Resistant starch] - gut microbiota, especially #Faecalibacterium, Predict postprandial glucose response (PPGR) after eating potatoes. [1.29] - #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. - #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. [1.31] [#Acyl-alkyl phosphatidylcholines] - #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. [1.32] [#Clostridium bolteae] - These four species were #Clostridium citroniae, C. bolteae, #Tyzzerella nexilis, and #Ruminococcus gnavus. [1.33] [#Obesity] [#Yogurt consumption] - yogurt intake impacts the hepatic metabolome, notably maintaining the levels of branched chain hydroxy acids (BCHA) which correlate with improved metabolic parameters [1.34] [#Parkinson’s Disease] [#Oral administration of Metformin] - #Metformin reduces neuronal damage in the brains of PD patients via neuroprotection and the inhibition of oxidative stress and inflammatory responses, thus providing a novel strategy for the clinical treatment of PD. [1.35] - #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. - #Dimethylglycine, #Imidazole propionate, #Tryptophan, #kynurenine and #Indolelactate associated with increased risk of T2D [#Para-cresol] - 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. [#Short Chain Fatty Acid] - SCFAs-induced improvements in adipose tissue metabolism can prevent insulin resistance, while #Succinate improves the host insulin sensitivity while preventing obesity. [1.36] [#Antibiotic Therapy] - 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 [#High Fat Diet] - HFD caused a decrease in circulating GLP-1 levels, and this was reversed with #Vancomycin treatment [1.37] [#Obesity] - In healthy human subjects #Akkermansia muciniphila was associated to low body weight, low body fat proportion, reduced adipose tissue inflammation and reduced insulin resistance. [1.38] - 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. [1.39] [#Chronic periodontitis] - 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. - 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 - an increase in Bacteroides and a decrease in #Proteobacteria and #Acinetobacter are observed in Type 2 diabetes (T2D) [1.41] - #Fasting blood glucose levels for all participants were significantly lower after taking #Green Tea extract compared to levels after taking the placebo. - Decreased gut inflammation due to the #Green Tea treatment in all participants was established through an analysis that showed a reduction in pro-inflammatory proteins in fecal samples. - #Green Tea > small intestine permeability favorably decreased. [1.42] [#Short Chain Fatty Acid] - SCFA-associated GPR43 (G-coupled receptor 43) has also been shown to suppress insulin signaling activity, decrease fat accumulation in adipose tissue, and improve energy homeostasis balancing [1.43] [#Akkermansia muciniphila] [#Secondary bile acids, #Short Chain Fatty Acid] [#Oral administration of Metformin] - oral metformin has been shown to alter gut microbiome composition in obese adults with T2D, which was associated with secondary BA and FXR changes, resulting in improved insulin sensitivity - Metformin promotes colonization by SCFA-producing bacteria such as Akkermansia, Several studies of different ethnic populations with T2D and healthy individuals have demonstrated that metformin alters gut microbiome composition and is associated with changes in SCFA, BA, and C-peptide levels. [1.44] [#High FODMAP diet] - Individual FODMAPs can increase health-promoting bacteria, such as Akkermansia muciniphila and Bifidobacterium. - The term FODMAPs stands for poorly-absorbed fermentable oligosaccharides, disaccharides, monosaccharides, and polyols. [1.45] [#Short Chain Fatty Acid] - the functionalities of SCFAs towards body tissues are mainly involvin the SCFA-specific receptors free fatty acid receptor 2 (FFAR2) and free fatty acid receptor 3 (FFAR3). - Increased secretion of insulin after SCFAs treatments were reported in many studies, but contradicting evidence also exist in several other studies. [1.46] [#Indole sulfuric acid (ISA), #Indole-3-propionic acid] - The bacterially derived Trp metabolites indoles, IPA and #Indole sulfuric acid (ISA) are lower in blood samples from subjects with type 2 diabetes as compared to the lean controls. - Higher serum concentrations of IPA are also associated with a reduced prevalence of T2D. [#Tryptophan] [#Cow’s milk (Dietary Casein), #High fibre diet] - a higher milk intake and higher fiber intake were associated with a favorable profile of circulating Trp metabolites for T2D. [1.47] [#Blautia wexlerae] [#Oral administration of Blautia wexlerae] - Blautia genus, especially B. wexlerae, as a commensal bacterium that is inversely correlated with #Obesity and type 2 diabetes mellitus. - Oral administration of B. wexlerae to mice induce metabolic changes and anti-inflammatory effects that decrease both high-fat diet–induced #Obesity and diabetes. - The beneficial effects of B. wexlerae are correlated with unique amino-acid metabolism to produce S-adenosylmethionine, acetylcholine, and L-ornithine and carbohydrate metabolism resulting in the accumulation of amylopectin and production of succinate, lactate, and acetate, with simultaneous modification of the gut bacterial composition. - S-adenosylmethionine, acetylcholine, and L-ornithine have anti-inflammatory properties and modify aspects of host metabolism, such as lipid metabolism, indicating that these compounds are potential effector metabolites for controlling #Obesity and diabetes. [1.48] [#Short Chain Fatty Acid] [#Exercise training, #Fecal Microbiota Transplantation] - exercise-induced alterations in the gut microbiota correlated closely with improvements in glucose homeostasis and insulin sensitivity. - The microbiome of responders exhibited an enhanced capacity for biosynthesis of short-chain fatty acids and catabolism of branched-chain amino acids, whereas those of non-responders were characterized by increased production of metabolically detrimental compounds. - Fecal microbial transplantation from responders, but not non-responders, mimicked the effects of exercise on alleviation of insulin resistance in obese mice. [1.49] [#Gastric bypass surgery] - An increase in #Propionate and #Bile Acids after RYGB was associated with an increase in hormone peptide tyrosine tyrosine (PYY) in humans and, hence, resolution of diabetes. [#Coprococcus etes] - There are 36 different strains of #Butyrate-producing bacteria, and five of them are associated with increased insulin sensitivity: #Coprococcus etes, #Oscillibacter sp. CAG 241, #Alistipes finegoldi and #Faecalibacterium prausnitzii. - The genus #Coprococcus was associated with higher insulin sensitivity and disposition index and a lower rate of dysglycemia. [#Flavonifractor plutii] - #Flavonifractor plutii and #Anaerostipes cacae ( #Butyrate-producing bacteria), paradoxically seem to increase the risk of developing some types of diabetes. - #Flavonifractor was associated with lower insulin sensitivity and disposition index and higher prevalence of dysglycemia. [1.51] - there was an inverse association between fecal #2-phenylpropionate and T2D - gut microbes were strongly associated with fecal levels of #Acetic acid and #Butyric acid , but were not associated with blood #Acetic acid or #Butyric acid. - The fecal #Butyric acid levels were inversely (beneficially) associated with T2D. - higher fecal #Butyric acid levels were associated with improved insulin response. - the concentration of fecal #Butyric acid was lower in T2D participants compared to those without T2D. - fecal #hydrocinnamic acid levels were inversely associated with T2D [1.52] [#Diabetes Type 1, #Pulmonary tubercolosis, #Tuberculosis] - the microbiota in latent TB infection group displayed a similar alpha-diversity but different beta-diversity, featuring decrease of Prevotella_9, Streptococcus, and Actinomyces and increase of Bacteroides, Alistipes, and Blautia at the genus level. [1.53] [#Diabetes Type 1] - Compared to the levels in non-diabetic individuals, diabetes patients exhibited a higher abundance of #Neisseria, TM7, #Gemella, #Eikenella, #Selenomonas, #Actinomyces, #Capnocytophaga, #Fusobacterium, #Aggregatibacter, #Veillonella, and #Streptococcus genera and a lower abundance of Filifactor, Synergistetes, Tannerella, Eubacterium, Porphyromonas, and Treponema genera [1.54] - A reduction in the #Lachnospira, #Roseburia, #Faecalibacterium and #Coprococcus genera in the T2D group. - These genera were #Butyrate producers. - The decrease of these genera favored #Obesity and the development of diseases. [#Short Chain Fatty Acid] - In four other genera (#Fusicatenibacter, #Agathobacter, #Butyricicoccus, #Marvinbryantia), a decrease in the T2D group could also be detected. All genera produce short-chain fatty acids - A significant reduction of genera #Alistipes, #Anaerostipes, #Ruminococcus was detected in the T2D group. - The genus #Blautia was one of the most represented genera in both groups enriched in group T2D. - #Lachnoclostridium were more abundant in the microbiome profiles of diabetic patients. - There are anomalies in the genera #Bacteroides and #Prevotella, both of which are increased in the T2D, both genera are #Propionate producers. - The reduction of #Subdoligranulum can also be assumed to have a negative impact and is thus characteristic of type 2 diabetes mellitus disease. [1.55] [#Irritable bowel syndrome] - Increased levels of #Ceramides were reported in mucosal samples from IBS patients as well as in plasma and tissue samples in diabetes, cardiomyopathy, insulin resistance, #Atherosclerosis and #Steatohepatitis. [1.56] [1.57] [#Beta-glucan] - Enrichment of #Candida albicans in samples from individuals with T2D. - Repopulation with C. albicans in HFD mice accelerated insulin resistance and related disorders. - β-glucan from C. albicans mirrored the deteriorating effect of C. albicans through the dectin-1 dependent pathway. [#Imidazole propionate] - Imidazole propionates (ImP), produced by several bacterial strains, including #Streptococcus mutans and #Eggerthella lenta, which was found to be elevated in individuals with T2DM and impairs insulin signaling through activation of the p38γ-p62-mTORC1 pathway [#Glycoursodeoxycholic acid] [#Oral administration of Metformin] - GUDCA, an endogenous bile acid conversed by gut bacteria, was found to be increased by metformin treatment and improve insulin sensitivity though an intestinal FXR dependent pathway [1.58] Diabetes : - The gut–brain–beta cell glucagon-like peptide-1 (GLP-1)-dependent axis and the clock genes both control insulin secretion. - GLP-1sensitivity is maximal during the dark feeding period, i.e., the postprandial state. - The abundance of ileum bacteria, particularly #Ruminococcaceae and #Lachnospiraceae, oscillated diurnally, with a maximum during the dark period, along with expression patterns of a subset of clock genes. - This diurnal pattern of circadian gene expression and #Lachnospiraceae abundance was also observed in two separate mouse models of gut microbiota dysbiosis and of autonomic neuropathy with impaired GLP-1 sensitivity. [1.59] - In periodontitis-associated type 2 diabetes (T2D), #Streptococcus and #Veillonella are dominant in the symbiosis network, and microbial shifts may contribute to systemic inflammation and metabolic dysfunction [#Anaerobutyricum soehngenii] - treatment with A. soehngenii was safe and observed a significant correlation between the measured fecal abundance of administered A. soehngenii and improvement in peripheral insulin sensitivity after 4 weeks of treatment. [1.61] [#Obesity] - Microbial homeostasis is normally maintained by peroxisome proliferator-activated receptor gamma (PPAR-γ). - PPAR-γ is a nuclear receptor activated by #Butyrate and other ligands, is found in adipocytes and colonocytes, and is responsible for activating genes involved in #Glucose and lipid metabolism. [1.62] [#Resistant starch] - #Ruminococcus was shown to possess an exceptional ability to colonize and degrade #Starch particles, which in turn alleviates insulin resistance. [1.63] [#Polyphenols] - #Blueberries (genus Vaccinium sect. Cyanococcus) are amongst the best studied polyphenol-rich fruit, and mechanistic and epidemiological studies have indicated a reduced risk of cardiovascular disease, type 2 diabetes, and death, as well as improved brain and possibly visual function with regular consumption [1.64] [#Glucose, #Short Chain Fatty Acid] - SCFA #Acetate activates GPR43, promoting GLP-1 release from colonic L cells. [#Glucose] - activation of GPR41 by #Propionate or #Butyrate can induce both GLP-1 and peptide YY secretion from L cells in the small intestine. [#Olive] - EVOO added to meals was associated with a reduction in blood #Glucose, #Triglyceride, apolipoprotein B-48, and dipeptidyl peptidase-4 activity levels and a significant increase in insulin and glucagon-like peptide 1 (GLP-1) levels in the peripheral blood. [1.65] - genus Actinobacterium #Collinsella was confirmed to be associated with #Alzheimer’s disease, as well as #Rheumatoid Arthritis, #Atherosclerosis, and type 2 diabetes. [#Short Chain Fatty Acid] - The relation between SCFAs and insulin sensitivity stems from the capacity of SCFAs to stimulate the secretion of GLP-1 by intestinal L-cells via G protein receptors, which has a significant impact on insulin release. [1.66] [#Low fibre Diet] - Enriched #Collinsella was widely reported in low-fiber diets and metabolic diseases (e.g., type 2 diabetes) [1.67] [#Peripheral neuropathy] [#Sphingomyelin] [#High Fat Diet] - #Lactobacillus, #Lachnoclostridium, and #Anaerotruncus taxa variants positively correlated with several lipid species, particularly elevated plasma sphingomyelins and sciatic nerve triglycerides. - In type 2 diabetes patients, #Lachnoclostridium correlated positively with total #Cholesterol and low-density lipoprotein #Cholesterol and a poorer metabolic profile [1.68] - CACS-associated species were also found positively associated with #Imidazole propionate, a microbially derived metabolite from #Histidine, reported to impair #Glucose metabolism. [1.69] [#Dipeptidyl peptidase 4] [#High Fat Diet] - microbial DPP4 was mainly produced by #Bacteroides spp. - Gut microbial DPP4 (mDPP4) could degrade active #GLP-1(7-37) in vitro. - mDPP4 could not affect active #GLP-1 levels in chow-fed mice but could decrease active #GLP-1 activity and impair #Glucose homeostasis in high-fat diet (HFD)–fed mice or dextran #Sulfate sodium/indomethacin–treated mice, suggesting that a damaged gut barrier is required for mDPP4 to affect the activity of host #GLP-1. - Gut microbial DPP4 isozyme can impair host #Glucose homeostasis, and variations in microbial DPP4 activities could possibly contribute to the heterogeneous responses to sitagliptin observed among patients with T2D. [#Glucose] - #Kombucha lowered average #Fasting blood glucose levels at 4 weeks compared to baseline - despite the #Sugar used in the fermentation process of #Kombucha, daily consumption did not raise #Fasting blood glucose levels to unhealthy levels in diabetics. [#Metabolic associated fatty liver disease] - #Kombucha > improve glycemic parameters, including #Glucose tolerance, and attenuate symptoms associated with nonalcoholic fatty liver disease in obese mice. - #Kombucha also contains #Acetic acid, which has been reported to have anti-diabetic properties. - #Kombucha significantly lowered both glycemic and insulin indices compared to consumption of a #Glucose solution. [1.71] [#Tryptophan] - #5-hydroxytryptamine (5-HT) is a Trp-catabolite formed by Trp hydroxylase 1 enzyme. - It promotes insulin secretion from pancreatic β-cells and inhibits hyperglycaemia and #Obesity. - Gut microbiomes can convert #Arginine (Arg) into #Agmatine. - It has many roles to inhibit diabetes, as it can increase HbA1C level, serum insulin level and can restore insulin sensitivity. [#Bacteroides ovatus, #Paraclostridium bifermentans] - Various gut bacterial species, like #Bacteroides thetaiotaomicron, B. ovatus, #Clostridium limosum, and C. bifermentans metabolize amino acid #Tryptophan (Trp) to #Indole. - It helps to secret glucagon-like-peptide-1 (GLP-1), which has an important role to increase insulin secretion and inhibit glucagon secretion. [#Short Chain Fatty Acid] - A few examples of SCFA-producing bacteria are #Blautia hydrogenotrophica and #Marvinbryantia formatexigens, #Veillonella spp., #Dialister spp etc. - Levels of SCFAs in T2DM patients are always lower than the healthy subjects. - The mechanism of action of SCFA includes promoting insulin secretion, improving insulin sensitivity, activating intestinal gluconeogenesis, increasing energy expenditure, reducing fat accumulation and inflammation. - They promote the production of satiety hormones and reduce the feeling of appetite. - The #Tyrosine decarboxylase action of bacteria #Ruminococcus gnavus, #Enterococcus faecalis and #Clostridium sporogenes converts #Tyrosine (Tyr) into #Tyramine. - Its role to improve #Glucose tolerance marked it as a beneficial metabolite to T2DM. - #Histidine is the source #Imidazole propionate metabolite. It is negatively correlated with diabetes. - It hampers #Glucose tolerance, insulin signaling, #Glucose metabolism disorder, and causes systemic inflammation. - Chronic T2DM patients show a markedly high plasma level of #TMAO. It increases the risk of cardiovascular disease and mortality among the patients. - #TMAO promotes metabolic dysfunction, insulin resistance, adipose tissue inflammation, and hepatic gluconeogenesis. [1.72] [#CVD, #Obstructive sleep apnea-hypopnea syndrome] - people with DM who developed OSA were at a greater risk of developing CVDs by over 50% [#CVD, #Obstructive sleep apnea-hypopnea syndrome] - OSA is associated with repetitive episodes of hypoxia–reoxygenation, triggering a cascade of metabolic and inflammatory changes that exacerbate pre-existing metabolic and cardiovascular risk factors in diabetes. - OSA is linked with impaired #Glucose metabolism and increased insulin resistance, leading to further inflammation, endothelial dysfunction, and the development of atherosclerosis and CVDs. - Individuals with diabetes who developed OSA face a greater risk of peripheral neuropathy (PN), AF, diabetic foot disease (DFD), CKD, and all-cause mortality when compared with diabetics without OSA. [1.73] [#Oral administration of Metformin] - #Faecalibacterium prausnitzii > significant decrease in patients with T2DM treated with #Metformin alone, while no significant decrease was observed in patients treated with #Metformin combined with #Benaglutide. [1.74] - #Vitamin D has shown significant effect on regulates insulin resistance, and there is a significant inverse association between serum #Vitamin D level and IR. [1.75] [#Allergy] - A disturbed #Proteobacteria microbiota has been previously associated with #Psoriasis, eczema and diabetic foot ulcers, with greater #Proteobacteria diversity correlated with T-helper1, interleukin-10 and anti-inflammatory immune responses that were protective against allergic inflammation. [1.76] - After 4 weeks on a #Pecan-rich diet, changes in serum insulin, insulin resistance (HOMA-IR) and beta cell function (HOMA-β) were significantly greater than after the control diet. - #Pecan consumption also lowered the risk of cardiometabolic disease as indicated by a composite score reflecting changes in clinically relevant markers. [1.77] - #Butyrate has also been considered as a therapeutic target for the treatment of Type 2 diabetes [1.78] - An endogenous activator (3-iodothyronamine) of TAAR1 has recently been shown to improve glycemic control by promoting insulin secretion in beta-cells. [#Irritable bowel syndrome] [#Ruminococcus gnavus] [#High fibre diet] - fiber intervention significantly suppressed #Tryptamine and #Phenethylamine levels and abundances of R. gnavus in T2D subjects, revealing manipulation of gut microbiota-derived #Tryptamine and #Phenethylamine by dietary changes or prebiotics is a potential direction for managing #Metabolic syndrome and IBS. [#Irritable bowel syndrome] [#Ruminococcus gnavus] - #Tryptamine and phenethylamine derived from the R. gnavus-mediated catabolism on dietary amino acids impaired insulin sensitivity via activation of TAAR1-MAPK/ERK signaling pathway axis, thereby contributing to insulin resistance in gut dysbiosis-associated IBS and T2D. [#Blautia hansenii] - increased abundances of other #Tryptamine and #Phenethylamine producer B. hansenii in #Metabolic syndrome - #Tryptamine and #Phenethylamine can stimulate insulin secretion but both acute and long-term exposure to TAAR1 activators #Tryptamine and #Phenethylamine impair insulin sensitivity [#Ruminococcus gnavus] - #Tryptamine/#Phenethylamine-mediated TAAR1 signaling pathway as the key molecular axis underlying R. gnavus-induced insulin resistance [1.79] [#Berberine] [#High Fat Diet] - The increase in #Fasting plasma #Glucose, #Fasting insulin, and homeostasis model assessment of insulin resistance (HOMA-IR) caused by HFD feeding decreased after BBR treatmen - #Lachnospiraceae UCG-001 abundance was inversely associated with DNAme in the promoter region of four metabolically relevant genes, including those involved in insulin secretion. [1.81] [#Obesity] - the higher dose of #Propyl propane thiosulfinate (PTS) improved #Glucose and hepatic homeostasis, modulated lipid metabolism, and increased the thermogenic capacity of brown adipose tissue. [1.82] [#Keto diet] - KD has been shown to lead to the reduction of hyperinsulinemia and the improvement of insulin sensitivity in patients with type 2 diabetes [1.83] - faecal carbohydrates, particularly host-accessible monosaccharides, are increased in individuals with insulin resistance and are associated with microbial carbohydrate metabolisms and host inflammatory cytokines. - Excessive monosaccharides have the potential to promote ectopic lipid accumulation while also activating immune cells, leading to low-grade inflammation and Insulin Resistance [#Alistipes indistinctus] - Postprandial blood #Glucose levels were particularly reduced in mice administered with A. indistinctus, #Alistipes finegoldii and #Bacteroides thetaiotaomicron that were fed a high-fat diet. - Insulin tolerance tests also revealed that these strains ameliorated IR, most prominently by A. indistinctus administration. - A. indistinctus administration ameliorated body mass gain, ectopic triglyceride accumulation in the liver and #Glucose intolerance - Serum levels of HDL-C, adiponectin and, to a lesser extent, triglycerides, were also improved in mice that were treated with A. indistinctus. - carbohydrate oxidation was significantly reduced in mice that were treated with A. indistinctus, implying that carbohydrate use is limited. - A. indistinctus administration substantially altered caecal metabolites, characterized by a reduction in several carbohydrates including #Fructose, a lipogenic monosaccharide. - #Fructose was similarly reduced in the serum - The AUC of insulin tolerance test was positively correlated with the caecal monosaccharides #Fructose, #Glucose and #Mannose [#Alistipes indistinctus] - A. indistinctus administration improves lipid accumulation and thereby Insulin Resistance, while simultaneously reducing intestinal monosaccharide levels. - #Fructose is a widely recognized risk factor for inflammation and Insulin Resistance due to its role in lipid accumulation [1.84] [#Prevotella copri] [#Branched-chain amino acids] - In individuals with insulin resistance, BCAA levels were high, according to metabolomic analysis. - These levels were attributed, at least in part, to the overabundance of P. copri in the gut microbiome of these patients. - Mice developed insulin resistance and a high BCAAs level when orally administered P. copri. [#Prevotella copri] - Patients with T2D, especially those on #Metformin only (rather than #Metformin and glibenclamide), had a higher relative abundance of P. copri than healthy controls [1.85] - #Resveratrol also showed promising potential for the treatment of #Diabetic ulcers. - #Resveratrol prevented #Hyperglycemia-induced endothelial dysfunction and angiogenic impairment by activating endothelial SIRT1 and promoting forkhead box O1 (FOXO1) degradation, following a de-repression of c-Myc expression. [#Obesity] - #Resveratrol mimics #Caloric restriction via the activation of #Sirtuin 1 (SIRT 1) resulting in improved exercise performance and insulin sensitivity, as well as showing body fat-lowering effects by inhibiting adipogenesis, and increasing lipid mobilisation in adipose tissue. [1.86] [#Hepatocellular cancer, #Metabolic associated fatty liver disease] - Among people with NAFLD, the presence of type 2 diabetes is associated with a significantly higher risk of hepatic decompensation and hepatocellular carcinoma. [1.87] [#Sugar-sweetened beverage] - high intake of #Sugar-sweetened carbonated beverage (SSCB) was more associated with the prevalence of #Depression. - the risk of depressive symptom significantly increased proportionally to SSCB consumption. - The effects appeared to be the same between those with pre-diabetic risk and those with normal blood #Sugar — which suggests insulin resistance or blood #Sugar levels don’t appear to play a part in determining risk for #Depression symptoms. [1.88] [1.89] [#Metabolic syndrome, #Obesity] - #Irisin is involved in promoting the browning of white adipose tissue, the regulation of energy metabolism, and the improvement of insulin resistance. - #Irisin is increased in DM type 2 and perhaps in association with pro-atherogenic endothelial disorders. - fenugreek seeds can downregulate serum #Irisin levels, thus improved liver and kidney function in patients with DM type 2. - The study also showed that #Irisin concentration was downregulated during the amelioration of DM type 2 - #Vitamin D supplementation may improve DM type 2 by decreasing glycosylated hemoglobin (HbA1c) and increasing #Sirtuin 1 (SIRT1) and #Irisin in #Vitamin D-deficient patients with DM type 2 [#Metabolic associated fatty liver disease] [#Meat-based diet] - Consumption of processed meat, red meat, soda, biscuits, and cakes has been linked to insulin resistance and NAFLD. [1.91] - in T2DM patients > #Bifidobacterium, #Lactobacillus, #Faecalibacterium prausnitzii, and #Butyrate-creating bacteria such as #Roseburia intestinalis and F. prausnitzii abundance decreased - #Proteobacteria and #Clostridium abundance increased in T2DM patients - #Imidazole propionate is produced at higher concentrations from #Histidine in a gut simulator when fecal microbiota from T2DM patients is used, and that it impairs #Glucose tolerance when administered to mice. - #Imidazole propionate inhibits insulin signal transduction at the receptor level by activating p38 mitogen-activated protein kinase (MAPK), promoting p62 phosphorylation, and then activating the mechanical target of rapamycin complex 1 (mTORC1), which may contribute to T2DM pathogenesis [1.92] - #Blautia produces #Acetic acid and significantly correlates with host physiological dysfunctions, such as #Obesity, diabetes, and various inflammatory diseases. - An increase in #Blautia abundance may inhibit insulin signaling and prevent fat accumulation in adipocytes [1.93] [#Diabetes Type 1] - Diabetes > #Butyrate can reduce proliferation of glomerular endothelial cells and potentially keep proliferation under control. [#Diabetes Type 1] - #Butyrate can reduce #Oxidative stress by improving mitochondrial function in STZ-treated pancreatic β-cells and neuronal cells. [1.94] [#Gallstone Disease, #Kidney stone, #Urinary stone disease] - #Eggerthella, #Flavonifractor, and #Ruminococcus spp., all of which were enriched in SF, have recently been suggested as general disease-associated signatures (shared across type 2 diabetes, diarrhoea and #Constipation, mental disorders, and gallstones) [1.95] [#L-urobilin] - urobilin > increased risk of T2DM [1.96] [#Metabolic syndrome] - Host-accessible monosaccharides such as #Fructose, #Galactose, #Mannose and #Xylose were increased in people with Insulin Resistance and MetS. The excess monosaccharides could promote lipid accumulation and activate immune cells, leading to an increased pro-inflammatory cytokine response in the host. - #Bacteroidales — particularly #Alistipes indistinctus — could metabolise the monosaccharides accumulated in the faeces of people with IR. - Transfer of IS-associated bacteria (#Alistipes indistinctus) reduced blood #Glucose and faecal monosaccharide levels, improved lipid accumulation and ameliorated IR. - IR and faecal monosaccharides were lower in individuals who harboured more #Bacteroidales-type #Bacteria in their gut, potentially highlighting the role of #Bacteroidales-type #Bacteria (#Bacteroides, #Alistipes) in mediating IS. - #Lachnospiraceae microbiome was associated with an excess of faecal monosaccharides. - the increased presence of #Lachnospiraceae (#Dorea, #Blautia) in the gut microbiota was positively correlated with IR. [1.97] [#Fusobacterium nucleatum, #Porphyromonas gingivalis, #Prevotella intermedia] - mice fed a high-fat diet, combined administration of P. gingivalis, F. nucleatum, and P. intermedia induced impaired blood #Glucose metabolism and insulin resistance with concomitant changes in the gut microbial composition. [1.98] [#Ruminococcus gnavus] - R. gnavus showed significantly higher abundance in patients with type 2 diabetes mellitus (T2DM) and #Prediabetes (PreDM). [#Ruminococcus gnavus] - R. gnavus was found to have a positive correlation with #Glycine #Ursodeoxycholic acid (GUDCA) levels, which have been shown to improve metabolism by promoting fat thermogenesis [1.99] - #Metabolic syndrome, which involves a number of factors including HTN, #Hyperlipidemia, #Obesity, and insulin resistance, is more frequently reported in patients with #Migraine - increase in IR-enriched skin genera such as #Peptoniphilus and Intrasporangium (Figure S3D) during the course of a respiratory viral infection, while a decline in specific genera in the stool microbiome known for #Butyrate production, like Clostridium_IV, Lawsonibacter, and #Intestinimonas. [1.101] - An increased presence of #Anaerostipes in the gut microbiota has been linked to an enhancement in glomerular filtration rate and a positive impact on renal function. - Individuals with type 2 diabetes exhibit a decreased abundance of #Anaerostipes in their gut compared to those in good health [1.102] - #Quercetin has also shown to abolish NLRP3 inflammasome activation in macrophages by upregulating Akt signaling, reducing insulin resistance in mice with particulate matter-induced metabolic disorder [#Aging] - #Resveratrol administration to older #Adult diabetics showed to improve mitochondrial biogenesis and function through SIRT1 upregulation, alleviating the oxidative damage and promoting insulin sensitivity [1.103] - Metabolites associated with the identified fiber-related bacteria (Both #Butyrivibrio and #Faecalibacterium) , including several microbial metabolites (eg, #Indolepropionate and #3-phenylpropionate) inversely associated with the risk of T2D. [#High fibre diet] - multiple bacterial genera, species, and related enzymes associated with fiber intake. Several bacteria (eg, #Butyrivibrio, #Faecalibacterium) and enzymes involved in fiber degradation (eg, xylanase EC3.2.1.156) were positively associated with fiber intake, inversely associated with prevalent T2D, and favorably associated with T2D-related metabolic traits. [1.104] [#Metabolic syndrome] - #Phospholipids are implicated in the development of metabolic disease and critical modulators of insulin sensitivity. - #Sphingolipids play a role in the development of diabetes and the emergence of vascular complications [1.105] - oral #Fusobacterium nucleatum and gut #Lactobacillus are increased in in diabetic coronary heart disease (DCHD) patients, with a positive correlation between the two. - in hyperglycemic mice, augmented #Fusobacterium nucleatum levels in the oral cavity were accompanied by an imbalance in the oral-gut axis, characterized by an increased coexistence of #Fusobacterium nucleatum and #Lactobacillus, along with elevated cardiac miRNA-21 and a greater extent of myocardial damage [1.106] - #Blautia, #Faecalibacterium, #Bifidobacterium, #Clostridium, #Anaerostipes, #Mediterraneibacter, and #Butyricicoccus abundances were relatively higher in healthy fecal samples than in prediabetic fecal samples. - #Streptococcus and #Eggerthella were relatively more abundant than in prediabetic fecal samples. - #Bacteroides, #Phascolarctobacterium, #Parabacteroides, and #Paraprevotella were more abundant in prediabetic fecal samples. - #Clostridium induces regulatory T cells to the colon and allows lymphocytes to enter inflamed islet cells to regulate the inflammatory response, thereby inhibiting diabetic morbidity [1.107] [#Secondary bile acids] - stimulating the G-protein-coupled receptor 5 by gut-bacteria-derived secondary BAs influences #Glucose homeostasis through glucagon-like peptide-1 (#GLP-1) action. [1.108] - duodenal single dose infusion of #Anaerobutyricum soehngenii stimulated glucagon-like peptide-1 (#GLP-1) production, ameliorated glycemic control [1.109] [#Constitutive androstane receptor , #Metabolic associated fatty liver disease] [#3,3′-Diindolylmethane] - CAR plays a critical role in regulating the breakdown, uptake and removal of foreign substances in the liver, including drugs. - CAR plays a role in diabetes, fatty liver disease and small intestine #Ulcerative Colitis - The diindoles, diindolylmethane (DIM) and #Diindolylethane (DIE) selectively up-regulate bona fide CAR target genes in primary human hepatocytes and mouse liver without causing significant side effects. - 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 lipoproteins. - 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. [1.111] - Faecalibacterium prausnitzii, an indicator of inflammation, shows a decreased abundance in diabetes and obese persons.References Notes [1.146]
