Metformin {60000057} Record Keys Parent:[ ] Definition:Metformin Queue:[ ] Details Initialisation date:2020-09-21 Specification: N,N-dimethylbiguanideSource: [ ] LinksInfolink Meta Information Structural Type:[ ] Functional Type:[ ] Function:[ ] Notes: - Lactate uptake by the liver is diminished with metformin use because lactate is a substrate for hepatic gluconeogenesis, a process that metformin inhibits. - Metformin has been suggested as increasing production of lactate in the large intestine. - Epidemiological studies first recognized a relationship with metformin use in T2DM patients and reduced colorectal cancer (CRC) risk. (2) - metformin treatment significantly increase Escherichia coli and lowers Intestinibacter abundance. - This effect is thought to be mediated by metformin’s effect on short-chain fatty acid (butyrate)-producing bacteria and the abundance of Akkermansia muciniphila, as well as through common biological pathways and genes encoded in different metformin-affected bacteria. (3) -bcat-1 knockdown increases mitochondrial respiration and induces oxidative damage in neurons through mammalian target of rapamycin-independent mechanisms. Increased mitochondrial respiration, or "mitochondrial hyperactivity," is required for bcat-1(RNAi) neurotoxicity. -Post-disease-onset administration of the type 2 diabetes medication metformin reduces mitochondrial respiration to control levels and significantly improves both motor function and neuronal viability.(4)Shared Reference Notes [1.1] - metformin treatment, shifts a depletion of butyrate-producing taxa in T2D patient. These in turn cause functional microbiome shifts, in part alleviated by metformin-induced changes. [1.2] [#Diabetes Type 2] - 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. [1.3] [#Diabetes Type 2] - 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 [1.4] [#Oral administration of Metformin] - Metformin, decreased leaky gut and inflammation in high-fat diet-fed older obese mice, by beneficially modulating the gut microbiota. - Metformin increased goblet cell mass and mucin production in the obese older gut, thereby decreasing leaky gut and inflammation. - Metformin treatment slightly increased Bacteroidetes in HFD-fed mice compared to their untreated HFD-fed counterparts. - The abundance of genera belonging to S24_7, Ruminococcaceae and Lactococcus were increased, while that of Coriobacteriaceae, Lactobacillus, Dorea, SMB53, Roseburia and Veilonellaceae, and Dehalobacterium was significantly decreased in the gut of metformin-treated HFD-fed older mice compared to their HFD-fed controls. - Similarly, the proportion of Clostridiales;g, Lachnospiraceae;g, and Ruminococcus was significantly increased while that of genus Sutterella was significantly decreased in metformin-treated LFD-fed mice compared to their LFD-fed counterparts. - The abundance of 5-aminopantanoate_1, propionate and butyrate was increased while that of 5-aminopentanoate_2, ethanol, sarcosine, formate, creatinine, propylene glycol, and several others were decreased in metformin-treated LFD-fed older mice compared to untreated LFD-fed controls. Similarly, the abundance of taurine, butyrate, total bile acids_1, propionate, and leucine was increased while that of creatinine, sarcosine, glutamate, pyruvate, and formate was significantly decreased in the feces of metformin-treated HFD-fed older mice compared to their untreated HFD-fed counterparts . Metformin caused highest increase in butyrate and taurine and highest decrease in creatinine and sarcosine abundance in the gut of older mice . [1.5] [#Diabetes Type 2, #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. [1.6] [#Parkinson’s Disease] - metformin-mediated AMPK activation may reduce the level of neuronal loss and alleviate several phenotypes associated with these disorders. - a metformin therapy for more than 4 years significantly decreased the risk of developing both PD and AD. [1.7] [#Diabetes Type 2] [#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. [1.8] [#Diabetes Type 2] [#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 [1.9] [#Bilophila wadsworthia] [#High Fat Diet] - HFD-induced increase of (B. wadsworthia) which is bile-tolerant was further aggravated by #Silymarin/#Silibinin treatment. - B. wadsworthia was sensitive to the environmental redox changes as the abundance of this bacterium was also found largely increased in vitro upon exposure of metformin - abundance of #Escherichia/#Shigella was found increased by both #Silymarin and metformin [#β-blocker] - A total of 46 associations were identified between microbial composition and single medications, exemplified by the depletion of #Akkermansia muciniphila by β-blockers and #Statins, and the enrichment of #Escherichia/#Shigella and depletion of #Bacteroides xylanisolvens by metformin. [#Statins] - depletion of #Romboutsia and #Butyriciocccus by statin plus metformin. [1.11] [#Breast cancer, #Cancer] [#Keto diet] - animals treated with the combination regimen showed significantly lower tumor burden, higher tumor latency and slower tumor growth. - lowering systemic #Glucose by this combined dietary and pharmacologic approach improved overall survival in our mouse model by 31 days, which is approximately equivalent to 3 human years. [1.12] [#Short Chain Fatty Acid] - adults with #Prediabetes > metformin > increased the abundance of GM SCFA-producing bacteria M (#Fusicatenibacter and #Blautia) - adults with #Prediabetes > linagliptin/metformin > Roseburia, Bifidobacterium, and [Eubacterium] hallii group.References Notes (1) [1.13] (3) [1.14]
