Metabolism: clinical and experimental最新文献

{"title":"Dr. James B. Field: an obituary (1926-2023).","authors":"Stergios A Polyzos, Michael A Hill, Christos S Mantzoros","doi":"10.1016/j.metabol.2024.155956","DOIUrl":"https://doi.org/10.1016/j.metabol.2024.155956","url":null,"abstract":"","PeriodicalId":18694,"journal":{"name":"Metabolism: clinical and experimental","volume":"158 ","pages":"155956"},"PeriodicalIF":10.8,"publicationDate":"2024-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141727503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dr. James B. Field: an obituary (1926–2023)","authors":"Stergios A. Polyzos , Michael A. Hill , Christos S. Mantzoros","doi":"10.1016/j.metabol.2024.155956","DOIUrl":"10.1016/j.metabol.2024.155956","url":null,"abstract":"","PeriodicalId":18694,"journal":{"name":"Metabolism: clinical and experimental","volume":"158 ","pages":"Article 155956"},"PeriodicalIF":10.8,"publicationDate":"2024-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141469436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dr. James B. Field: An obituary (1926 - 2023).","authors":"Stergios A Polyzos, Michael A Hill, Christos S Mantzoros","doi":"10.1016/j.metabol.2024.155956","DOIUrl":"https://doi.org/10.1016/j.metabol.2024.155956","url":null,"abstract":"","PeriodicalId":18694,"journal":{"name":"Metabolism: clinical and experimental","volume":" ","pages":"155956"},"PeriodicalIF":10.8,"publicationDate":"2024-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141443022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lactate and lactylation in cardiovascular diseases: current progress and future perspectives","authors":"Wengen Zhu ,&nbsp;Siyu Guo ,&nbsp;Junyi Sun ,&nbsp;Yudan Zhao ,&nbsp;Chen Liu","doi":"10.1016/j.metabol.2024.155957","DOIUrl":"10.1016/j.metabol.2024.155957","url":null,"abstract":"<div><p>Cardiovascular diseases (CVDs) are often linked to structural and functional impairments, such as heart defects and circulatory dysfunction, leading to compromised peripheral perfusion and heightened morbidity risks. Metabolic remodeling, particularly in the context of cardiac fibrosis and inflammation, is increasingly recognized as a pivotal factor in the pathogenesis of CVDs. Metabolic syndromes further predispose individuals to these conditions, underscoring the need to elucidate the metabolic underpinnings of CVDs. Lactate, a byproduct of glycolysis, is now recognized as a key molecule that connects cellular metabolism with the regulation of cellular activity. The transport of lactate between different cells is essential for metabolic homeostasis and signal transduction. Disruptions to lactate dynamics are implicated in various CVDs. Furthermore, lactylation, a novel post-translational modification, has been identified in cardiac cells, where it influences protein function and gene expression, thereby playing a significant role in CVD pathogenesis. In this review, we summarized recent advancements in understanding the role of lactate and lactylation in CVDs, offering fresh insights that could guide future research directions and therapeutic interventions. The potential of lactate metabolism and lactylation as innovative therapeutic targets for CVD is a promising avenue for exploration.</p></div>","PeriodicalId":18694,"journal":{"name":"Metabolism: clinical and experimental","volume":"158 ","pages":"Article 155957"},"PeriodicalIF":10.8,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141440683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The lipopolysaccharide-TLR4 axis regulates hepatic glutaminase 1 expression promoting liver ammonia build-up as steatotic liver disease progresses to steatohepatitis","authors":"Maria Mercado-Gómez ,&nbsp;Naroa Goikoetxea-Usandizaga ,&nbsp;Annarein J.C. Kerbert ,&nbsp;Leire Uraga Gracianteparaluceta ,&nbsp;Marina Serrano-Maciá ,&nbsp;Sofia Lachiondo-Ortega ,&nbsp;Rubén Rodriguez-Agudo ,&nbsp;Clàudia Gil-Pitarch ,&nbsp;Jorge Simón ,&nbsp;Irene González-Recio ,&nbsp;Marcos F. Fondevila ,&nbsp;Pablo Santamarina-Ojeda ,&nbsp;Mario F. Fraga ,&nbsp;Rubén Nogueiras ,&nbsp;Javier de las Heras ,&nbsp;Rajiv Jalan ,&nbsp;María Luz Martínez-Chantar ,&nbsp;Teresa C. Delgado","doi":"10.1016/j.metabol.2024.155952","DOIUrl":"10.1016/j.metabol.2024.155952","url":null,"abstract":"<div><h3>Introduction</h3><p>Ammonia is a pathogenic factor implicated in the progression of metabolic-associated steatotic liver disease (MASLD). The contribution of the glutaminase 1 (GLS) isoform, an enzyme converting glutamine to glutamate and ammonia, to hepatic ammonia build-up and the mechanisms underlying its upregulation in metabolic-associated steatohepatitis (MASH) remain elusive.</p></div><div><h3>Methods</h3><p>Multiplex transcriptomics and targeted metabolomics analysis of liver biopsies in dietary mouse models representing the whole spectra of MASLD were carried out to characterize the relevance of hepatic GLS during disease pathological progression. In addition, the acute effect of liver-specific GLS inhibition in hepatic ammonia content was evaluated in cultured hepatocytes and in <em>in vivo</em> mouse models of diet-induced MASLD. Finally, the regulatory mechanisms of hepatic GLS overexpression related to the lipopolysaccharide (LPS)/Toll-like receptor 4 (TLR4) axis were explored in the context of MASH.</p></div><div><h3>Results</h3><p>In mouse models of diet-induced MASLD, we found that augmented liver GLS expression is closely associated with the build-up of hepatic ammonia as the disease progresses from steatosis to steatohepatitis. Importantly, the acute silencing/pharmacological inhibition of GLS diminishes the ammonia burden in cultured primary mouse hepatocytes undergoing dedifferentiation, in steatotic hepatocytes, and in a mouse model of diet-induced steatohepatitis, irrespective of changes in ureagenesis and gut permeability. Under these conditions, GLS upregulation in the liver correlates positively with the hepatic expression of TLR4 that recognizes LPS. In agreement, the pharmacological inhibition of TLR4 reduces GLS and hepatic ammonia content in LPS-stimulated mouse hepatocytes and hyperammonemia animal models of endotoxemia.</p></div><div><h3>Conclusions</h3><p>Overall, our results suggest that the LPS/TLR4 axis regulates hepatic GLS expression promoting liver ammonia build-up as steatotic liver disease progresses to steatohepatitis.</p></div>","PeriodicalId":18694,"journal":{"name":"Metabolism: clinical and experimental","volume":"158 ","pages":"Article 155952"},"PeriodicalIF":10.8,"publicationDate":"2024-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0026049524001793/pdfft?md5=12dd951c3edc7c390a38f8a2de860484&pid=1-s2.0-S0026049524001793-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141437207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of the plasma metabolome and lipidome in response to sleeve gastrectomy and gastric bypass surgeries reveals molecular patterns of surgical weight loss","authors":"Minoo Bagheri ,&nbsp;Kahraman Tanriverdi ,&nbsp;Mark D. Iafrati ,&nbsp;Jonathan D. Mosley ,&nbsp;Jane E. Freedman ,&nbsp;Jane F. Ferguson","doi":"10.1016/j.metabol.2024.155955","DOIUrl":"10.1016/j.metabol.2024.155955","url":null,"abstract":"<div><h3>Objectives</h3><p>Bariatric surgery improves metabolic health, but the underlying mechanisms are not fully understood. We analyzed the effects of two types of bariatric surgery, sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB), on the plasma metabolome and lipidome.</p></div><div><h3>Methods</h3><p>We characterized the plasma metabolome (1268 metabolites) and lipidome (953 lipids) pre-operatively and at 3 and 12 months post-operatively in 104 obese adults who were previously recruited to a prospective cohort of bariatric surgery. The metabolomic and lipidomic responses to bariatric surgery over time were analyzed using multivariable linear mixed-effects models.</p></div><div><h3>Results</h3><p>There were significant changes in multiple metabolites and lipids, including rapid early changes in amino acid and peptide metabolites, including decreases in branched-chain amino acids (BCAAs), aromatic AAs, alanine and aspartate, and increases in glycine, serine, arginine and citrulline. There were also significant decreases in many triglyceride species, with increases in phosphatidylcholines and phosphatidylethanolamines. There were significant changes in metabolites related to energy metabolism that were apparent only after 12 months. We observed differences by bariatric surgery type in the changes in a small number of primary and secondary bile acids, including glycohyocholate and glyco-beta-muricholate.</p></div><div><h3>Conclusions</h3><p>Our findings highlight the comprehensive changes in metabolites and lipids that occur over the 12 months following bariatric surgery. While both SG and RYGB caused profound changes in the metabolome and lipidome, RYGB was characterized by greater increases in bile acids following surgery.</p></div>","PeriodicalId":18694,"journal":{"name":"Metabolism: clinical and experimental","volume":"158 ","pages":"Article 155955"},"PeriodicalIF":10.8,"publicationDate":"2024-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0026049524001823/pdfft?md5=6ed83a1bd2670d692913f60803513498&pid=1-s2.0-S0026049524001823-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141437206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting the regulation of iron homeostasis as a potential therapeutic strategy for nonalcoholic fatty liver disease","authors":"Yutong Sui ,&nbsp;Xue Geng ,&nbsp;Ziwei Wang ,&nbsp;Jing Zhang ,&nbsp;Yanqun Yang ,&nbsp;Ziyu Meng","doi":"10.1016/j.metabol.2024.155953","DOIUrl":"10.1016/j.metabol.2024.155953","url":null,"abstract":"<div><p>With aging and the increasing incidence of obesity, nonalcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease worldwide. NAFLD mainly includes simple hepatic steatosis, nonalcoholic steatohepatitis (NASH), liver fibrosis and hepatocellular carcinoma (HCC). An imbalance in hepatic iron homeostasis is usually associated with the progression of NAFLD and induces iron overload, reactive oxygen species (ROS) production, and lipid peroxide accumulation, which leads to ferroptosis. Ferroptosis is a unique type of programmed cell death (PCD) that is characterized by iron dependence, ROS production and lipid peroxidation. The ferroptosis inhibition systems involved in NAFLD include the solute carrier family 7 member 11 (SLC7A11)/glutathione (GSH)/glutathione peroxidase 4 (GPX4) and ferroptosis suppressor protein 1 (FSP1)/coenzyme Q10 (CoQ10)/nicotinamide adenine dinucleotide phosphate (NADPH) regulatory axes. The main promotion system involved is the acyl-CoA synthetase long-chain family (ACSL4)/arachidonic lipoxygenase 15 (ALOX15) axis. In recent years, an increasing number of studies have focused on the multiple roles of iron homeostasis imbalance and ferroptosis in the progression of NAFLD. This review highlights the latest studies about iron homeostasis imbalance- and ferroptosis-associated NAFLD, mainly including the physiology and pathophysiology of hepatic iron metabolism, hepatic iron homeostasis imbalance during the development of NAFLD, and key regulatory molecules and roles of hepatic ferroptosis in NAFLD. This review aims to provide innovative therapeutic strategies for NAFLD.</p></div>","PeriodicalId":18694,"journal":{"name":"Metabolism: clinical and experimental","volume":"157 ","pages":"Article 155953"},"PeriodicalIF":9.8,"publicationDate":"2024-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141414053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hepatic noradrenergic innervation acts via CREB/CRTC2 to activate gluconeogenesis during cold","authors":"Henrique J.N. Morgan ,&nbsp;Heitor B.P. Delfino ,&nbsp;Aline Z. Schavinski ,&nbsp;Samuel A. Malone ,&nbsp;Camille Charoy ,&nbsp;Natany G. Reis ,&nbsp;Ana P. Assis ,&nbsp;Natalia Lautherbach ,&nbsp;Wilian A. Silveira ,&nbsp;Lilian C. Heck ,&nbsp;Dan Guton ,&nbsp;Ana I. Domingos ,&nbsp;Isis C. Kettelhut ,&nbsp;Marc Montminy ,&nbsp;Luiz C.C. Navegantes","doi":"10.1016/j.metabol.2024.155940","DOIUrl":"10.1016/j.metabol.2024.155940","url":null,"abstract":"<div><h3>Background and aim</h3><p>Although it is well established that hormones like glucagon stimulates gluconeogenesis <em>via</em> the PKA-mediated phosphorylation of CREB and dephosphorylation of the cAMP-regulated CREB coactivators CRTC2, the role of neural signals in the regulation of gluconeogenesis remains uncertain.</p></div><div><h3>Methods and results</h3><p>Here, we characterize the noradrenergic bundle architecture in mouse liver; we show that the sympathoexcitation induced by acute cold exposure promotes hyperglycemia and upregulation of gluconeogenesis <em>via</em> triggering of the CREB/CRTC2 pathway. Following its induction by dephosphorylation, CRTC2 translocates to the nucleus and drives the transcription of key gluconeogenic genes. Rodents submitted to different models of sympathectomy or knockout of CRTC2 do not activate gluconeogenesis in response to cold. Norepinephrine directly acts in hepatocytes mainly through a Ca²⁺-dependent pathway that stimulates CREB/CRTC2, leading to activation of the gluconeogenic program.</p></div><div><h3>Conclusion</h3><p>Our data demonstrate the importance of the CREB/CRTC2 pathway in mediating effects of hepatic sympathetic inputs on glucose homeostasis, providing new insights into the role of norepinephrine in health and disease.</p></div>","PeriodicalId":18694,"journal":{"name":"Metabolism: clinical and experimental","volume":"157 ","pages":"Article 155940"},"PeriodicalIF":10.8,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0026049524001677/pdfft?md5=6c1ed4a0e78f64e999d79245a6b4e2d5&pid=1-s2.0-S0026049524001677-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141327681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Global, regional, and national trends in metabolic risk factor-associated mortality among the working-age population from 1990-2019: An age-period-cohort analysis of the Global Burden of Disease 2019 study","authors":"Xiao-Lu Lin ,&nbsp;Qing-Wei Zhang ,&nbsp;Gui-Fen Chen ,&nbsp;Shi-Jie Yang ,&nbsp;Xiao-Bo Li ,&nbsp;Wan-Yin Deng","doi":"10.1016/j.metabol.2024.155954","DOIUrl":"10.1016/j.metabol.2024.155954","url":null,"abstract":"<div><h3>Background</h3><p>Metabolic diseases contribute significantly to premature mortality worldwide, with increasing burdens observed among the working-age population (WAP). This study assessed global, regional, and national trends in metabolic disorders and associated mortality over three decades in WAP.</p></div><div><h3>Methods</h3><p>Data from the Global Burden of Disease 2019 study were leveraged to assess global metabolism-associated mortality and six key metabolic risk factors in WAP from 1990-2019. An age-period-cohort model was employed to determine the overall percentage change in mortality.</p></div><div><h3>Results</h3><p>The 2019 global metabolic risk-related mortality rate in WAP rose significantly by 50.73%, while the age-standardized mortality rate declined by 21.5%. India, China, Indonesia, the USA, and the Russian Federation were the top contributing countries to mortality in WAP, accounting for 51.01% of the total. High systolic blood pressure (HSBP), high body mass index (HBMI), and high fasting plasma glucose (HFPG) were the top metabolic risk factors for the highest mortality rates. Adverse trends in HBMI-associated mortality were observed, particularly in lower sociodemographic index (SDI) regions. HFPG-related mortality declined globally but increased in older age groups in lower SDI countries.</p></div><div><h3>Conclusions</h3><p>Despite a general decline in metabolic risk-related deaths in WAP, increasing HBMI- and HFPG-related mortality in lower SDI areas poses ongoing public health challenges. Developing nations should prioritize interventions addressing HBMI and HFPG to mitigate mortality risks in WAP.</p></div>","PeriodicalId":18694,"journal":{"name":"Metabolism: clinical and experimental","volume":"157 ","pages":"Article 155954"},"PeriodicalIF":9.8,"publicationDate":"2024-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141327680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metformin-induced changes in the gut microbiome and plasma metabolome are associated with cognition in men","authors":"Marisel Rosell-Díaz ,&nbsp;Anna Petit-Gay ,&nbsp;Clàudia Molas-Prat ,&nbsp;Laura Gallardo-Nuell ,&nbsp;Lluís Ramió-Torrentà ,&nbsp;Josep Garre-Olmo ,&nbsp;Vicente Pérez-Brocal ,&nbsp;Andrés Moya ,&nbsp;Mariona Jové ,&nbsp;Reinald Pamplona ,&nbsp;Josep Puig ,&nbsp;Rafael Ramos ,&nbsp;Fredrik Bäckhed ,&nbsp;Jordi Mayneris-Perxachs ,&nbsp;José Manuel Fernández-Real","doi":"10.1016/j.metabol.2024.155941","DOIUrl":"10.1016/j.metabol.2024.155941","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;p&gt;An altered gut microbiome characterized by reduced abundance of butyrate producing bacteria and reduced gene richness is associated with type 2 diabetes (T2D). An important complication of T2D is increased risk of cognitive impairment and dementia. The biguanide metformin is a commonly prescribed medication for the control of T2D and metformin treatment has been associated with a significant reduction in the risk of dementia and improved cognition, particularly in people with T2D.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Aim&lt;/h3&gt;&lt;p&gt;To investigate the associations of metformin use with cognition exploring potential mechanisms by analyzing the gut microbiome and plasma metabolome using shotgun metagenomics and HPLC-ESI-MS/MS, respectively.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;p&gt;We explored two independent cohorts: an observational study (Aging Imageomics) and a phase IV, randomized, double-blind, parallel-group, randomized pilot study (MEIFLO). From the two studies, we analyzed four study groups: (1) individuals with no documented medical history or medical treatment (&lt;em&gt;n&lt;/em&gt; = 172); (2) people with long-term T2D on metformin monotherapy (&lt;em&gt;n&lt;/em&gt; = 134); (3) people with long-term T2D treated with oral hypoglycemic agents other than metformin (&lt;em&gt;n&lt;/em&gt; = 45); (4) a newly diagnosed T2D subjects on metformin monotherapy (&lt;em&gt;n&lt;/em&gt; = 22). Analyses were also performed stratifying by sex.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;p&gt;Several bacterial species belonging to the Proteobacteria (&lt;em&gt;Escherichia coli&lt;/em&gt;) and Verrucomicrobia (&lt;em&gt;Akkermansia muciniphila&lt;/em&gt;) phyla were positively associated with metformin treatment, while bacterial species belonging to the Firmicutes phylum (&lt;em&gt;Romboutsia timonensis&lt;/em&gt;, &lt;em&gt;Romboutsia ilealis&lt;/em&gt;) were negatively associated. Due to the consistent increase in &lt;em&gt;A. muciniphila&lt;/em&gt; and decrease in &lt;em&gt;R.ilealis&lt;/em&gt; in people with T2D subjects treated with metformin, we investigated the association between this ratio and cognition. In the entire cohort of metformin-treated T2D subjects, the &lt;em&gt;A.muciniphila&lt;/em&gt;/&lt;em&gt;R.ilealis&lt;/em&gt; ratio was not significantly associated with cognitive test scores. However, after stratifying by sex, the &lt;em&gt;A.muciniphila&lt;/em&gt;/&lt;em&gt;R. ilealis&lt;/em&gt; ratio was significantly and positively associated with higher memory scores and improved memory in men.&lt;/p&gt;&lt;p&gt;Metformin treatment was associated with an enrichment of microbial pathways involved in the TCA cycle, and butanoate, arginine, and proline metabolism in both cohorts. The bacterial genes involved in arginine metabolism, especially in production of glutamate (&lt;em&gt;astA, astB, astC, astD, astE, putA&lt;/em&gt;), were enriched following metformin intake. In agreement, in the metabolomics analysis, metformin treatment was strongly associated with the amino acid proline, a metabolite involved in the metabolism of glutamate.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;p&gt;The beneficial effects of metformin may be mediated by changes in the compositi","PeriodicalId":18694,"journal":{"name":"Metabolism: clinical and experimental","volume":"157 ","pages":"Article 155941"},"PeriodicalIF":9.8,"publicationDate":"2024-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0026049524001689/pdfft?md5=0306d82cc1c5aa62af161906acde9ece&pid=1-s2.0-S0026049524001689-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141317744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}