Gut microbiota: A new target for T2DM prevention and treatment

Frontiers in Endocrinology, Journal Year: 2022, Volume and Issue: 13

Published: Aug. 11, 2022

Type 2 diabetes mellitus (T2DM), one of the fastest growing metabolic diseases, has been characterized by disorders including hyperglycemia, hyperlipidemia and insulin resistance (IR). In recent years, T2DM become disease in world. Studies have indicated that patients with are often associated intestinal flora dysfunction involving multiple organs. Metabolites flora, such as bile acids (BAs), short-chain fatty (SCFAs) amino (AAs)may influence to some extent decreased sensitivity regulate well immune homeostasis. this paper, we review changes gut mechanisms which microbiota modulates metabolites affecting T2DM, may provide a basis for early identification T2DM-susceptible individuals guide targeted interventions. Finally, also highlight microecological therapeutic strategies focused on shaping inform improvement progression.

Language: Английский

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Effects of caloric restriction on the gut microbiome are linked with immune senescence

Microbiome, Journal Year: 2022, Volume and Issue: 10(1)

Published: April 4, 2022

Caloric restriction can delay the development of metabolic diseases ranging from insulin resistance to type 2 diabetes and is linked both changes in composition function gut microbiota immunological consequences. However, interaction between dietary intake, microbiome, immune system remains poorly described.We transplanted an obese female before (AdLib) after (CalRes) 8-week very-low-calorie diet (800 kcal/day) into germ-free mice. We used 16S rRNA sequencing evaluate taxa with differential abundance AdLib- CalRes-microbiota recipients single-cell multidimensional mass cytometry define signatures murine colon, liver, spleen. Recipients CalRes sample exhibited overall higher alpha diversity restructuring decreased several microbial (e.g., Clostridium ramosum, Hungatella hathewayi, Alistipi obesi). Transplantation mice their body fat accumulation improved glucose tolerance compared AdLib-microbiota recipients. Finally, CalRes-associated reduced levels intestinal effector memory CD8+ T cells, B hepatic CD4+ cells.Caloric shapes microbiome which improve health may induce a shift towards naïve cell compartment and, thus, senescence. Understanding role as mediator beneficial effects low calorie diets on inflammation metabolism enhance new therapeutic treatment options for diseases.NCT01105143 , "Effects negative energy balance muscle regulation," registered 16 April 2010. Video Abstract.

Language: Английский

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Interplay of Metabolome and Gut Microbiome in Individuals With Major Depressive Disorder vs Control Individuals

JAMA Psychiatry, Journal Year: 2023, Volume and Issue: 80(6), P. 597 - 597

Published: April 19, 2023

Importance Metabolomics reflect the net effect of genetic and environmental influences thus provide a comprehensive approach to evaluating pathogenesis complex diseases, such as depression. Objective To identify metabolic signatures major depressive disorder (MDD), elucidate direction associations using mendelian randomization, evaluate interplay human gut microbiome metabolome in development MDD. Design, Setting Participants This cohort study used data from participants UK Biobank (n = 500 000; aged 37 73 years; recruited 2006 2010) whose blood was profiled for metabolomics. Replication sought PREDICT BBMRI-NL studies. Publicly available summary statistics 2019 genome-wide association depression were randomization (individuals with MDD 59 851; control individuals 113 154). Summary metabolites obtained OpenGWAS MRbase 118 000). depression, performed Dutch cohorts. Data analyzed March December 2021. Main Outcomes Measures lifetime recurrent MDD, 249 nuclear magnetic resonance spectroscopy Nightingale platform. Results The included 6811 compared 51 446 4370 62 508 individuals. Individuals younger (median [IQR] age, 56 [49-62] years vs 58 [51-64] years) more often female (4447 [65%] 2364 [35%]) than Metabolic consisted 124 spanning energy lipid metabolism pathways. Novel findings 49 metabolites, including those involved tricarboxylic acid cycle (ie, citrate pyruvate). Citrate significantly decreased (β [SE], −0.07 [0.02]; FDR 4 × 10 −04 ) pyruvate increased 0.04 0.02) Changes observed these particularly lipoproteins, consistent differential composition microbiota belonging order Clostridiales phyla Proteobacteria / Pseudomonadota Bacteroidetes Bacteroidota . Mendelian suggested that fatty acids intermediate very large density lipoproteins changed disease process but high-density did not. Conclusions Relevance showed disturbed may play role

Language: Английский

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A modified Mediterranean-style diet enhances brain function via specific gut-microbiome-brain mechanisms

Gut Microbes, Journal Year: 2024, Volume and Issue: 16(1)

Published: March 6, 2024

Alzheimer's disease (AD) is a debilitating brain disorder with rapidly mounting prevalence worldwide, yet no proven AD cure has been discovered. Using multi-omics approach in transgenic mouse model, the current study demonstrated efficacy of modified Mediterranean-ketogenic diet (MkD) on AD-related neurocognitive pathophysiology and underlying mechanisms related to gut-microbiome-brain axis. The findings revealed that MkD induces profound shifts gut microbiome community microbial metabolites. Most notably, promoted growth Lactobacillus population, resulting increased bacteria-derived lactate production. We discovered elevated levels microbiome- diet-derived metabolites serum as well, signaling their influence brain. Importantly, these changes upregulated specific receptors have neuroprotective effects induced alternations neuroinflammatory-associated pathway profiles hippocampus. Additionally, displayed strong favorable co-regulation relationship gut-brain integrity inflammatory markers, well neurobehavioral outcomes. underscore ameliorative neurological function communication via modulation microbiome-metabolome arrays.

Language: Английский

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Immune checkpoint blockade reprograms systemic immune landscape and tumor microenvironment in obesity-associated breast cancer

Cell Reports, Journal Year: 2021, Volume and Issue: 35(12), P. 109285 - 109285

Published: June 1, 2021

Immune checkpoint blockade (ICB) has improved outcomes in some cancers. A major limitation of ICB is that most patients fail to respond, which partly attributable immunosuppression. Obesity appears improve immune therapies cancers, but impacts on breast cancer (BC) remain unknown. In lean and obese mice, tumor progression reprogramming were quantified BC tumors treated with anti-programmed death-1 (PD-1) or control. augments incidence progression. Anti-PD-1 induces regression mice potently abrogates mice. primes systemic immunity be highly responsive obesity, leading greater immunosuppression, may explain anti-PD-1 efficacy. significantly reinvigorates antitumor despite persistent obesity. Laminin subunit beta-2 (Lamb2), downregulated by anti-PD-1, predicts patient survival. Lastly, a microbial signature associated efficacy identified. Thus, efficacious reinvigorating durable immunity.Video abstracthttps://www.cell.com/cms/asset/411585c2-4b9b-4c33-989f-3bd379b0504f/mmc4.mp4Loading ...(mp4, 8.42 MB) Download video

Language: Английский

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Diet Alters Entero-Mammary Signaling to Regulate the Breast Microbiome and Tumorigenesis

Cancer Research, Journal Year: 2021, Volume and Issue: 81(14), P. 3890 - 3904

Published: June 3, 2021

Abstract Obesity and poor diet often go hand-in-hand, altering metabolic signaling thereby impacting breast cancer risk outcomes. We have recently demonstrated that dietary patterns modulate mammary microbiota populations. An important largely open question is whether the microbiome of gut gland mediates effects on cancer. To address this, we performed fecal transplants between mice control or high-fat diets (HFD) recorded tumor outcomes in a chemical carcinogenesis model. HFD induced protumorigenic effects, which could be mimicked animals fed by transplanting HFD-derived microbiota. Fecal altered both populations, suggesting link microbiomes. increased serum levels bacterial lipopolysaccharide (LPS), diet–derived transplant reduced LPS bioavailability HFD-fed animals. In vitro models normal epithelium showed disrupts tight junctions (TJ) compromises epithelial permeability. mice, from expression TJ-associated genes gland. Furthermore, infecting cells with an proliferation, implicating tumor-associated bacteria signaling. double-blind placebo-controlled clinical trial patients administered fish oil supplements before primary resection, intervention modulated tumors tissue. This study demonstrates effect Significance: shifts microenvironment to affect tumorigenesis, oral interventions can

Language: Английский

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Insoluble yeast β-glucan attenuates high-fat diet-induced obesity by regulating gut microbiota and its metabolites

Carbohydrate Polymers, Journal Year: 2022, Volume and Issue: 281, P. 119046 - 119046

Published: Jan. 4, 2022

Language: Английский

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Eucommiae cortex polysaccharides mitigate obesogenic diet-induced cognitive and social dysfunction via modulation of gut microbiota and tryptophan metabolism

Theranostics, Journal Year: 2022, Volume and Issue: 12(8), P. 3637 - 3655

Published: Jan. 1, 2022

The high fat and sucrose diet, known as the obesogenic diet (OD), has been related to low-grade chronic inflammation neurodevelopmental disorders. Emerging evidence suggests that OD influences cognitive social function via gut-brain axis. However, effects of during adolescence on future health have unclear. Meanwhile, underlying mechanisms effective interventions are not fully understood. Polysaccharides, one most abundant substances in

Language: Английский

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Precision Nutrition: Recent Advances in Obesity

Physiology, Journal Year: 2022, Volume and Issue: 38(1), P. 42 - 50

Published: Sept. 20, 2022

"Precision nutrition" is an emerging area of nutrition research that focuses on understanding metabolic variability within and between individuals helps develop customized dietary plans interventions to maintain optimal individual health. It encompasses nutritional genomic (gene-nutrient interactions), epigenetic, microbiome, environmental factors. Obesity a complex disease affected by genetic factors thus relevant target precision nutrition-based approaches. Recent studies have shown significant associations obesity phenotypes (body weight, body mass index, waist circumference, central regional adiposity) variants, epigenetic (DNA methylation noncoding RNA), microbial species, environment (sociodemographics physical activity). Additionally, also the interactions metabolites, affect energy balance adiposity. These include variants in

Language: Английский

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Faecal Microbiota transplantation affects liver DNA methylation in Non-alcoholic fatty liver disease: a multi-omics approach

Gut Microbes, Journal Year: 2023, Volume and Issue: 15(1)

Published: June 14, 2023

Individuals with nonalcoholic fatty liver disease (NAFLD) have an altered gut microbiota composition. Moreover, hepatic DNA methylation may be in the state of NAFLD. Using a fecal transplantation (FMT) intervention, we aimed to investigate whether change composition relates assessed plasma metabolite profiles by FMT relate changes methylation. Twenty-one individuals NAFLD underwent three 8-weekly vegan allogenic donor (n = 10) or autologous 11) FMTs. We obtained from paired biopsies study participants before and after applied multi-omics machine learning approach identify microbiome, peripheral blood metabolome methylome, analyzed cross-omics correlations. Vegan compared induced distinct differential I) profiles, including increased abundance Eubacterium siraeum potential probiotic Blautia wexlerae; II) metabolites, levels phenylacetylcarnitine (PAC) phenylacetylglutamine (PAG) both gut-derived phenylacetic acid, several choline-derived long-chain acylcholines; III) most importantly Threonyl-TRNA Synthetase 1 (TARS) Zinc finger protein 57 (ZFP57). Multi-omics analysis showed that Gemmiger formicillis Firmicutes bacterium_CAG_170 positively correlated PAC PAG. E negatively cg16885113 ZFP57. Alterations caused widespread metabolites (e.g. PAC, PAG, metabolites) These results indicate FMTs might induce metaorganismal pathway changes, bacteria liver.

Language: Английский

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