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1.
Nutrients ; 13(10)2021 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-34684378

RESUMO

The use of nutritional interventions for managing diabetes is one of the effective strategies aimed at reducing the global prevalence of the condition, which is on the rise. Almonds are the most consumed tree nut and they are known to be rich sources of protein, monounsaturated fatty acids, essential minerals, and dietary fibre. Therefore, the aim of this review was to evaluate the effects of almonds on gut microbiota, glycometabolism, and inflammatory parameters in patients with type 2 diabetes. METHODS: This systematic review and meta-analysis was carried out according to the preferred reporting items for systematic review and meta-analysis (PRISMA). EBSCOhost, which encompasses the Health Sciences Research Databases; Google Scholar; EMBASE; and the reference lists of articles were searched based on population, intervention, control, outcome, and study (PICOS) framework. Searches were carried out from database inception until 1 August 2021 based on medical subject headings (MesH) and synonyms. The meta-analysis was carried out with the Review Manager (RevMan) 5.3 software. RESULTS: Nine randomised studies were included in the systematic review and eight were used for the meta-analysis. The results would suggest that almond-based diets have significant effects in promoting the growth of short-chain fatty acid (SCFA)-producing gut microbiota. Furthermore, the meta-analysis showed that almond-based diets were effective in significantly lowering (p < 0.05) glycated haemoglobin (HbA1c) levels and body mass index (BMI) in patients with type 2 diabetes. However, it was also found that the effects of almonds were not significant (p > 0.05) in relation to fasting blood glucose, 2 h postprandial blood glucose, inflammatory markers (C-reactive protein and Tumour necrosis factor α, TNF-α), glucagon-like peptide-1 (GLP-1), homeostatic model assessment of insulin resistance (HOMA-IR), and fasting insulin. The biological mechanisms responsible for the outcomes observed in this review in relation to reduction in HbA1c and BMI may be based on the nutrient composition of almonds and the biological effects, including the high fibre content and the low glycaemic index profile. CONCLUSION: The findings of this systematic review and meta-analysis have shown that almond-based diets may be effective in promoting short-chain fatty acid-producing bacteria and lowering glycated haemoglobin and body mass index in patients with type 2 diabetes compared with control. However, the effects of almonds were not significant (p > 0.05) with respect to fasting blood glucose, 2 h postprandial blood glucose, inflammatory markers (C-reactive protein and TNF-α), GLP-1, HOMA-IR, and fasting insulin.


Assuntos
Biomarcadores/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/microbiologia , Inflamação/patologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Glicemia , Índice de Massa Corporal , Proteína C-Reativa/metabolismo , Diabetes Mellitus Tipo 2/sangue , Microbioma Gastrointestinal , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Hemoglobina A Glicada/metabolismo , Homeostase , Humanos , Insulina/sangue , Resistência à Insulina , Prunus dulcis , Viés de Publicação , Risco , Fator de Necrose Tumoral alfa/metabolismo
2.
PLoS One ; 16(10): e0258812, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34669745

RESUMO

Secretory IgA (SIgA) is released into mucosal surfaces where its function extends beyond that of host defense to include the shaping of resident microbial communities by mediating exclusion/inclusion of respective microbes and regulating bacterial gene expression. In this capacity, SIgA acts as the fulcrum on which host immunity and the health of the microbiota are balanced. We recently completed an analysis of the gut and salivary IgA-Biomes (16S rDNA sequencing of SIgA-coated/uncoated bacteria) in Mexican-American adults that identified IgA-Biome differences across the glycemic spectrum. As Th17:Treg ratio imbalances are associated with gut microbiome dysbiosis and chronic inflammatory conditions such as type 2 diabetes, the present study extends our prior work by examining the impact of Th17:Treg ratios (pro-inflammatory:anti-inflammatory T-cell ratios) and the SIgA response (Th17:Treg-SIgA axis) in shaping microbial communities. Examining the impact of Th17:Treg ratios (determined by epigenetic qPCR lymphocyte subset quantification) on the IgA-Biome across diabetes phenotypes identified a proportional relationship between Th17:Treg ratios and alpha diversity in the stool IgA-Biome of those with dysglycemia, significant changes in community composition of the stool and salivary microbiomes across glycemic profiles, and genera preferentially abundant by T-cell inflammatory phenotype. This is the first study to associate epigenetically quantified Th17:Treg ratios with both the larger and SIgA-fractionated microbiome, assess these associations in the context of a chronic inflammatory disease, and offers a novel frame through which to evaluate mucosal microbiomes in the context of host responses and inflammation.


Assuntos
Bactérias/classificação , Diabetes Mellitus Tipo 2/imunologia , Imunoglobulina A Secretora/metabolismo , RNA Ribossômico 16S/genética , Análise de Sequência de DNA/métodos , Linfócitos T Reguladores/imunologia , Células Th17/imunologia , Adulto , Bactérias/genética , Bactérias/isolamento & purificação , DNA Bacteriano/genética , DNA Ribossômico/genética , Diabetes Mellitus Tipo 2/microbiologia , Epigênese Genética , Feminino , Microbioma Gastrointestinal , Humanos , Masculino , Americanos Mexicanos , Pessoa de Meia-Idade , Filogenia
3.
Nutrients ; 13(9)2021 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-34579166

RESUMO

It is currently unknown whether associations between gut microbiota composition and type 2 diabetes (T2D) differ according to the ethnic background of individuals. Thus, we studied these associations in participants from two ethnicities characterized by a high T2D prevalence and living in the same geographical area, using the Healthy Life In Urban Settings (HELIUS) study. We included 111 and 128 T2D participants on metformin (Met-T2D), 78 and 49 treatment-naïve T2D (TN-T2D) participants, as well as a 1:1 matched group of healthy controls from, respectively, African Surinamese and South-Asian Surinamese descent. Fecal microbiome profiles were obtained through 16S rRNA gene sequencing. Univariate and machine learning analyses were used to explore the associations between T2D and the composition and function of the gut microbiome in both ethnicities, comparing Met-T2D and TN-T2D participants to their respective healthy control. We found a lower α-diversity for South-Asian Surinamese TN-T2D participants but no significant associations between TN-T2D status and the abundance of bacterial taxa or functional pathways. In African Surinamese participants, we did not find any association between TN-T2D status and the gut microbiome. With respect to Met-T2D participants, we identified several bacterial taxa and functional pathways with a significantly altered abundance in both ethnicities. More alterations were observed in South-Asian Surinamese. Some altered taxa and pathways observed in both ethnicities were previously related to metformin use. This included a strong negative association between the abundance of Romboutsia and Met-T2D status. Other bacterial taxa were consistent with previous observations in T2D, including reduced butyrate producers such as Anaerostipes hadrus. Hence, our results highlighted both shared and unique gut microbial biomarkers of Met-T2D in individuals from different ethnicities but living in the same geographical area. Future research using higher-resolution shotgun sequencing is needed to clarify the role of ethnicity in the association between T2D and gut microbiota composition.


Assuntos
Grupo com Ancestrais do Continente Africano/estatística & dados numéricos , Grupo com Ancestrais do Continente Asiático/estatística & dados numéricos , Diabetes Mellitus Tipo 2/etnologia , Microbioma Gastrointestinal , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/etiologia , Diabetes Mellitus Tipo 2/microbiologia , Feminino , Microbioma Gastrointestinal/genética , Humanos , Masculino , Pessoa de Meia-Idade , RNA Ribossômico 16S/genética , Suriname
4.
Nutrients ; 13(8)2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-34444839

RESUMO

Type 2 diabetes (T2D) is associated with an increased risk of cardiovascular disease (CVD). The gut microbiota may contribute to the onset and progression of T2D and CVD. The aim of this study was to evaluate the relationship between the gut microbiota and subclinical CVD in T2D patients. This cross-sectional study used echocardiographic data to evaluate the cardiac structure and function in T2D patients. We used a quantitative polymerase chain reaction to measure the abundances of targeted fecal bacterial species that have been associated with T2D, including Bacteroidetes, Firmicutes, Clostridium leptum group, Faecalibacterium prausnitzii, Bacteroides, Bifidobacterium, Akkermansia muciniphila, and Escherichia coli. A total of 155 subjects were enrolled (mean age 62.9 ± 10.1 years; 57.4% male and 42.6% female). Phyla Bacteroidetes and Firmicutes and genera Bacteroides were positively correlated with the left ventricular ejection fraction. Low levels of phylum Firmicutes were associated with an increased risk of left ventricular hypertrophy. High levels of both phylum Bacteroidetes and genera Bacteroides were negatively associated with diastolic dysfunction. A high phylum Firmicutes/Bacteroidetes (F/B) ratio and low level of genera Bacteroides were correlated with an increased left atrial diameter. Phyla Firmicutes and Bacteroidetes, the F/B ratio, and the genera Bacteroides were associated with variations in the cardiac structure and systolic and diastolic dysfunction in T2D patients. These findings suggest that changes in the gut microbiome may be the potential marker of the development of subclinical CVD in T2D patients.


Assuntos
Doenças Cardiovasculares/microbiologia , Diabetes Mellitus Tipo 2/microbiologia , Angiopatias Diabéticas/microbiologia , Cardiomiopatias Diabéticas/microbiologia , Microbioma Gastrointestinal/fisiologia , Idoso , Estudos Transversais , Diabetes Mellitus Tipo 2/fisiopatologia , Ecocardiografia , Fezes/microbiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Volume Sistólico , Função Ventricular Esquerda
5.
Nutrients ; 13(6)2021 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-34205413

RESUMO

The aim of this research was to reveal the characteristics of gut microbiome altered by acarbose intervention in Japanese patients with type 2 diabetes (T2D) and its possible association with habitual dietary intake. Eighteen patients with T2D were administered acarbose for four weeks. The abundances of two major phyla, namely Actinobacteria and Bacteroidetes, were reciprocally changed accompanied by the acarbose intervention. There were also significant changes in the abundances of ten genera, including the greater abundance of Bifidobacterium, Eubacterium, and Lactobacillus and the lower abundance of Bacteroides in the group after the intervention than that before the intervention. Hierarchical clustering of habitual dietary intake was performed based on the pattern of changes in the gut microbiota and were classified into distinct three clusters. Cluster I consisted of sucrose, cluster II mainly included fat intake, and cluster III mainly included carbohydrate intake. Moreover, the amount of change in Faecalibacterium was positively correlated with the intake of rice, but negatively correlated with the intake of bread. The intake of potato was negatively correlated with the amount of change in Akkermansia and Subdoligranulum. Acarbose altered the composition of gut microbiome in Japanese patients with T2D, which might be linked to the habitual dietary intake.


Assuntos
Acarbose/administração & dosagem , Diabetes Mellitus Tipo 2/microbiologia , Dieta , Comportamento Alimentar/fisiologia , Microbioma Gastrointestinal/efeitos dos fármacos , Microbioma Gastrointestinal/fisiologia , Idoso , Bactérias/classificação , Bactérias/efeitos dos fármacos , Bactérias/genética , DNA Bacteriano/análise , Diabetes Mellitus Tipo 2/tratamento farmacológico , Carboidratos da Dieta/administração & dosagem , Gorduras na Dieta/administração & dosagem , Sacarose na Dieta/administração & dosagem , Fezes/microbiologia , Feminino , Inibidores de Glicosídeo Hidrolases , Humanos , Japão , Masculino , Pessoa de Meia-Idade
6.
Front Biosci (Schol Ed) ; 13(1): 17-29, 2021 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-34256527

RESUMO

Alzheimer's disease (AD) and type 2 diabetes mellitus (T2DM) share many common features including inflammation, oxidative stress and neuronal degeneration. Insulin resistance (IR) appears to be a common path in these pathological processes. IR is an early pathogenic event in AD, which leads to augmentation of hyperphosphorylated tau and Amyloid beta (Aß). The reviewed studies related to AD have revealed a positive association between T2DM and AD. This association was maintained in peripheral hyperinsulinemia cases without the presence of T2DM, which might be due to decreased insulin transport to the brain or the inadequate cerebral insulin production. Gut dysbiosis induces inflammation and consequently provokes both peripheral and cerebral IR and can amplify processes promoting AD. Additionally, the risk of increased progression of AD was revealed due to pre-diabetes, T2DM and gut dysbiosis. The pro-inflammatory changes might affect progression of AD pathology by inhibition of the autophago-lysosomal pathway and cerebral insulin signaling pathway. This review elaborates the role that cerebral IR might play in the underlying pathological events in AD.


Assuntos
Doença de Alzheimer , Diabetes Mellitus Tipo 2 , Disbiose , Resistência à Insulina , Doença de Alzheimer/metabolismo , Doença de Alzheimer/microbiologia , Peptídeos beta-Amiloides/metabolismo , Encéfalo/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/microbiologia , Humanos
7.
Biomed Pharmacother ; 138: 111094, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34311521

RESUMO

Currently, several studies propose that the dominant intestinal bacteria are core flora. Besides keeping the homeostasis of the intestinal environment, the intestinal microflora also plays a role in body metabolism, production of some vitamins, and control of barrier function. The study aimed to investigate the jejunum microbiota in diabetic rats as well as it's the relationship with Ceftriaxone sodium-mediated gut dysbiosis, diabetic parameters, and intestinal permeability. Thirty-two Wistar rats (Male) were enrolled and divided into four groups (A, B, C, and D; N = 8). Subsequently, T2DM was induced in C and D groups by HFD/STZ model and then gut dysbiosis in B and D groups via intragastric administration of Ceftriaxone sodium for two weeks. The food-water intake, body weight, fasting blood glucose, plasma insulin, HOMA-IR, intestinal permeability, and jejunum microbiota and it's histology were investigated. In this study, T2DM was associated with a significant decrease in the richness and diversity of jejunum microbiota, elevation in the intestinal permeability, and higher abundance of some opportunistic pathogens. Ceftriaxone sodium-induced gut dysbiosis declined food-water intake, damagedthe villi of jejunum tissue, increased intestinal permeability, and affected the diversity of jejunum microbiota. In diabetic rats, Ceftriaxone sodium-mediated gut dysbiosis also declined the abundance of someSCFAs bacteria and raised the abundant of some opportunistic bacteria such as Staphylococcus_sciuri. Interestingly, we found that several bacteria were negatively correlated with HOMA-IR, fasting blood glucose, body weight, and intestinal permeability. Overall, the study highlighted the jejunum microflora alterations in HFD/STZ diabetic rats and assessed the effect of Ceftriaxone sodium-induced gut dysbiosis on diabetic parameters, jejunum microbiota and histology, and intestinal permeability, which are of potential for further studies.


Assuntos
Antibacterianos/farmacologia , Bactérias/crescimento & desenvolvimento , Diabetes Mellitus Experimental/microbiologia , Diabetes Mellitus Tipo 2/microbiologia , Microbioma Gastrointestinal , Jejuno/microbiologia , Animais , Bactérias/efeitos dos fármacos , Bactérias/metabolismo , Ceftriaxona/farmacologia , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/induzido quimicamente , Diabetes Mellitus Tipo 2/metabolismo , Dieta Hiperlipídica , Disbiose , Microbioma Gastrointestinal/efeitos dos fármacos , Absorção Intestinal , Jejuno/efeitos dos fármacos , Jejuno/metabolismo , Masculino , Permeabilidade , Ratos Wistar , Estreptozocina
8.
Phytomedicine ; 87: 153582, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34091150

RESUMO

BACKGROUND AND PURPOSE: Diosmetin (Dios), a flavonoid compound with multiple pharmacological activities. However, fewer studies have reported its effects on type 2 diabetic mellitus (T2DM). Here, we address the effect of Dios on glucose metabolism and gut microbiota in KK-Ay diabetic mice. METHOD: Wild type C57BL/6 J mice or diabetic KK-Ay mice were treated with vehicle or Dios for one month. The ELISA kit and fluorescence microscope system were respectively employed to the evaluation of serum biochemical indicators and histopathological changes. Liver RNA-Seq and western blot were used to reveal the key signaling pathway. The effects of Dios on gut microbiota was investigated by the 16S rRNA gene sequencing, as well as the relationship between Dios and C. glu on glucose metabolism was explored with the C. glu transplantation. RESULTS: Dios treatment significantly decreased blood glucose and increased serum insulin concentrations. RNA-Seq analysis found that the underlying action mechanism of Dios on T2DM was via modulating glucose metabolism, which was proved by up-regulating IRS/PI3K/AKT signaling pathway to promote glycogen synthesis and GLUT4 translocation. Besides, Dios treatment reshaped the unbalanced gut microbiota by suppressing the ratio of Firmicutes/Bacteroidetes and markedly increasing the richness of C. glu. Moreover, treatment with C. glu and Dios together could markedly ameliorate glucose metabolism by up-regulating IRS/PI3K/AKT signaling pathway to promote glycogen synthesis and GLUT4 translocation. CONCLUSIONS: Dios treatment remarkably ameliorated glucose metabolism in KK-Ay diabetic mice by the regulation of C. glu via IRS/PI3K/AKT signaling pathway and reshaped the unbalanced gut microbiota. Our study provided evidence for the application of Dios to the treatment of T2DM.


Assuntos
Corynebacterium glutamicum/efeitos dos fármacos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Flavonoides/farmacologia , Hipoglicemiantes/farmacologia , Animais , Glicemia/metabolismo , Proteínas de Ligação a DNA/metabolismo , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/microbiologia , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/microbiologia , Microbioma Gastrointestinal/efeitos dos fármacos , Microbioma Gastrointestinal/genética , Glicogênio/metabolismo , Insulina/sangue , Insulina/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Ribossômico 16S , Fatores de Transcrição/metabolismo
9.
FASEB J ; 35(7): e21734, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34143451

RESUMO

Impaired glucose homeostasis in obesity is mitigated by enhancing the glucoregulatory actions of glucagon-like peptide 1 (GLP-1), and thus, strategies that improve GLP-1 sensitivity and secretion have therapeutic potential for the treatment of type 2 diabetes. This study shows that Holdemanella biformis, isolated from the feces of a metabolically healthy volunteer, ameliorates hyperglycemia, improves oral glucose tolerance and restores gluconeogenesis and insulin signaling in the liver of obese mice. These effects were associated with the ability of H. biformis to restore GLP-1 levels, enhancing GLP-1 neural signaling in the proximal and distal small intestine and GLP-1 sensitivity of vagal sensory neurons, and to modify the cecal abundance of unsaturated fatty acids and the bacterial species associated with metabolic health. Our findings overall suggest the potential use of H biformis in the management of type 2 diabetes in obesity to optimize the sensitivity and function of the GLP-1 system, through direct and indirect mechanisms.


Assuntos
Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/microbiologia , Firmicutes/fisiologia , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Camundongos Obesos/metabolismo , Camundongos Obesos/microbiologia , Animais , Glicemia/metabolismo , Modelos Animais de Doenças , Gluconeogênese/fisiologia , Glucose/metabolismo , Teste de Tolerância a Glucose/métodos , Hiperglicemia/metabolismo , Insulina/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/metabolismo , Obesidade/microbiologia
10.
J Endocrinol ; 250(2): R1-R21, 2021 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-34165440

RESUMO

Micronutrients influence hormone action and host metabolism. Dietary minerals, trace elements, and vitamins can alter blood glucose and cellular glucose metabolism, and several micronutrients are associated with the risk and progression of type 2 diabetes. Dietary components, microbes, and host immune, endocrine, and metabolic responses all interact in the intestine. There has been a focus on macronutrients modifying the host-microbe relationship in metabolic disease. Micronutrients are positioned to alter host-microbe symbiosis that participates in host endocrine control of glucose metabolism. Minerals and trace elements can alter the composition of the intestinal microbiota, gut barrier function, compartmentalized metabolic inflammation, cellular glucose transport, and endocrine control of glucose metabolism, including insulin and thyroid hormones. Dietary vitamins also influence the composition of the intestinal microbiota and vitamins can be biotransformed by gut microbes. Host-microbe regulation of vitamins can alter immunity, lipid and glucose metabolism, and cell fate and function of pancreatic beta cells. Causal effects of micronutrients in host-microbe metabolism are still emerging, and the mechanisms linking dietary excess or deficiency of specific micronutrients to changes in gut microbes directly linked to metabolic disease risk are not yet clear. Dietary fiber, fat, protein, and carbohydrates are key dietary factors that impact how microbes participate in host glucose metabolism. It is possible that micronutrient and microbiota-derived factors also participate in host-microbe responses that tip the balance in the endocrine control of host glucose metabolism. Dietary micronutrients should be considered, tested, and controlled in pre-clinical and clinical studies investigating host-microbe factors in metabolic diseases.


Assuntos
Glicemia/efeitos dos fármacos , Microbioma Gastrointestinal/efeitos dos fármacos , Microbioma Gastrointestinal/fisiologia , Micronutrientes/administração & dosagem , Animais , Diabetes Mellitus Tipo 2/microbiologia , Dieta , Sistema Endócrino/fisiologia , Feminino , Glucose/metabolismo , Controle Glicêmico , Humanos , Insulina , Masculino , Doenças Metabólicas/microbiologia , Obesidade/microbiologia , Gravidez , Vitaminas/administração & dosagem
11.
PLoS One ; 16(6): e0250855, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34161346

RESUMO

BACKGROUND: The gut microbiome may play a role in inflammation associated with type 2 diabetes (T2D) development. This cross-sectional study examined its relation with glycemic status within a subset of the Multiethnic Cohort (MEC) and estimated the association of circulating bacterial endotoxin (measured as plasma lipopolysaccharide-binding protein (LBP)) with T2D, which may be mediated by C-reactive protein (CRP). METHODS: In 2013-16, cohort members from five ethnic groups completed clinic visits, questionnaires, and stool and blood collections. Participants with self-reported T2D and/or taking medication were considered T2D cases. Those with fasting glucose >125 and 100-125 mg/dL were classified as undiagnosed (UT2D) and pre-diabetes (PT2D) cases, respectively. We characterized the gut microbiome through 16S rRNA gene sequencing and measured plasma LBP and CRP by standard assays. Linear regression was applied to estimate associations of the gut microbiome community structure and LBP with T2D status adjusting for relevant confounders. RESULTS: Among 1,702 participants (59.9-77.4 years), 735 (43%) were normoglycemic (NG), 506 (30%) PT2D, 154 (9%) UT2D, and 307 (18%) T2D. The Shannon diversity index decreased (ptrend = 0.05), while endotoxin, measured as LBP, increased (ptrend = 0.0003) from NG to T2D. Of 10 phyla, Actinobacteria (ptrend = 0.007), Firmicutes (ptrend = 0.003), and Synergistetes (ptrend = 0.02) were inversely associated and Lentisphaerae (ptrend = 0.01) was positively associated with T2D status. Clostridium sensu stricto 1, Lachnospira, and Peptostreptococcaceae were less, while Escherichia-Shigella and Lachnospiraceae were more abundant among T2D patients, but the associations with Actinobacteria, Clostridium sensu stricto 1, and Escherichia-Shigella may be due metformin use. PT2D/UT2D values were closer to NG than T2D. No indication was detected that CRP mediated the association of LBP with T2D. CONCLUSIONS: T2D but not PT2D/UT2D status was associated with lower abundance of SCFA-producing genera and a higher abundance of gram-negative endotoxin-producing bacteria suggesting that the gut microbiome may contribute to chronic systemic inflammation and T2D through bacterial translocation.


Assuntos
Diabetes Mellitus Tipo 2/microbiologia , Diabetes Mellitus Tipo 2/patologia , Microbioma Gastrointestinal/fisiologia , Idoso , Bactérias/genética , Estudos de Coortes , Estudos Transversais , Diabetes Mellitus Tipo 2/tratamento farmacológico , Fezes/microbiologia , Feminino , Microbioma Gastrointestinal/genética , Humanos , Masculino , Metformina/uso terapêutico , Pessoa de Meia-Idade , Estado Pré-Diabético/tratamento farmacológico , Estado Pré-Diabético/microbiologia , Estado Pré-Diabético/patologia , RNA Ribossômico 16S/genética
12.
Nat Commun ; 12(1): 2907, 2021 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-34006865

RESUMO

We propose microbiome disease "architectures": linking >1 million microbial features (species, pathways, and genes) to 7 host phenotypes from 13 cohorts using a pipeline designed to identify associations that are robust to analytical model choice. Here, we quantify conservation and heterogeneity in microbiome-disease associations, using gene-level analysis to identify strain-specific, cross-disease, positive and negative associations. We find coronary artery disease, inflammatory bowel diseases, and liver cirrhosis to share gene-level signatures ascribed to the Streptococcus genus. Type 2 diabetes, by comparison, has a distinct metagenomic signature not linked to any one specific species or genus. We additionally find that at the species-level, the prior-reported connection between Solobacterium moorei and colorectal cancer is not consistently identified across models-however, our gene-level analysis unveils a group of robust, strain-specific gene associations. Finally, we validate our findings regarding colorectal cancer and inflammatory bowel diseases in independent cohorts and identify that features inversely associated with disease tend to be less reproducible than features enriched in disease. Overall, our work is not only a step towards gene-based, cross-disease microbiome diagnostic indicators, but it also illuminates the nuances of the genetic architecture of the human microbiome, including tension between gene- and species-level associations.


Assuntos
Biologia Computacional/métodos , Microbioma Gastrointestinal/genética , Metagenoma/genética , Metagenômica/métodos , Microbiota/genética , Bactérias/classificação , Bactérias/genética , Análise por Conglomerados , Neoplasias Colorretais/genética , Neoplasias Colorretais/microbiologia , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/microbiologia , Firmicutes/genética , Firmicutes/fisiologia , Humanos , Doenças Inflamatórias Intestinais/genética , Doenças Inflamatórias Intestinais/microbiologia , Microbiota/fisiologia , Filogenia , Especificidade da Espécie
13.
J Microbiol ; 59(7): 693-701, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33990912

RESUMO

Due to the different rates of diabetes in different ethnic groups and the structural differences in intestinal microbiota, this study evaluated the changes in diabetes-related intestinal microbiota in two ethnic groups. Fifty-six stool samples were collected from subjects from the Han and Mongolian ethnic groups in China, including participants without diabetes (non-diabetic, ND) and with type 2 diabetes (T2D). The 16S rDNA gene V3 + V4 area was extracted from microbiota, amplified by PCR, and used to perform high-throughput sequencing and screen differential microbiota associated with ethnicity. The results showed that there were 44 T2D-related bacterial markers in the Han subjects, of which Flavonifractor, Alistipes, Prevotella, Oscillibacter, Clostridium XlVa, and Lachnospiracea_incertae_sedis were most closely related to diabetes. There were 20 T2D-related bacterial markers in the Mongolian subjects, of which Fastidiosipila and Barnesiella were most closely related to diabetes. The common markers of T2D bacteria in the two ethnic groups were Papillibacter and Bifidobacterium. There were 17 metabolic pathways with significant differences between the ND and T2D groups in the Han group, and 29 metabolic pathways in the Mongolian group. The glutamatergic metabolic pathway was the only common metabolic pathway in two ethnic groups. The composition and function of diabetes-related bacteria were significantly different among the different ethnic groups, which suggested that the influence of ethnic differences should be fully considered when studying the association between diabetes and bacteria. In addition, the common bacterial markers found in diabetic patients of different ethnic groups in this study can be used as potential targets to study the pathogenesis and treatment of diabetes.


Assuntos
Grupo com Ancestrais do Continente Asiático , Bactérias/classificação , Diabetes Mellitus Tipo 2/microbiologia , Grupos Étnicos , Microbioma Gastrointestinal , Adulto , Bactérias/genética , Bactérias/crescimento & desenvolvimento , Biomarcadores/análise , China , Diabetes Mellitus Tipo 2/metabolismo , Fezes/microbiologia , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Redes e Vias Metabólicas , Pessoa de Meia-Idade , RNA Ribossômico 16S/genética
14.
PLoS One ; 16(5): e0251245, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33983982

RESUMO

PURPOSE: Type 2 diabetes mellitus (T2DM) is an urgent public health problem and disproportionately affects Mexican Americans. The gut microbiome contributes to the pathophysiology of diabetes; however, no studies have examined this association in Mexican-Americans. The objective of this study was to compare gut microbiome composition between Mexican-Americans with and without T2DM. METHODS: This was a cross-sectional study of volunteers from San Antonio, TX. Subjects were 18 years or older and self-identified as Mexican American. Subjects were grouped by prior T2DM diagnosis. Eligible subjects attended a clinic visit to provide demographic and medical information. Thereafter, subjects recorded their dietary intake for three days and collected a stool sample on the fourth day. Stool 16s rRNA sequences were classified into operational taxonomic units (OTUs) via the mothur bayesian classifier and referenced to the Greengenes database. Shannon diversity and bacterial taxa relative abundance were compared between groups using the Wilcoxon rank sum test. Beta diversity was estimated using Bray-Curtis indices and compared between groups using PERMANOVA. RESULTS: Thirty-seven subjects were included, 14 (38%) with diabetes and 23 (62%) without diabetes. Groups were well-matched by body mass index and comorbid conditions. Shannon diversity was not significantly different between those with and without T2DM (3.26 vs. 3.31; p = 0.341). Beta diversity was not significantly associated with T2DM diagnosis (p = 0.201). The relative abundance of the most common bacterial phyla and families did not significantly differ between groups; however, 16 OTUs were significantly different between groups. CONCLUSIONS: Although alpha diversity was not significantly different between diabetic and non-diabetic Mexican Americans, the abundance of certain bacterial taxa were significantly different between groups.


Assuntos
Diabetes Mellitus Tipo 2/microbiologia , Microbioma Gastrointestinal/genética , Idoso , Bactérias/genética , Índice de Massa Corporal , Estudos Transversais , Diabetes Mellitus Tipo 2/metabolismo , Ingestão de Alimentos , Fezes/microbiologia , Feminino , Microbioma Gastrointestinal/fisiologia , Humanos , Masculino , Americanos Mexicanos/genética , Pessoa de Meia-Idade , Obesidade/metabolismo , RNA Ribossômico 16S/genética , Texas
15.
Nutrients ; 13(4)2021 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-33917736

RESUMO

The Mediterranean diet (MD) has been recommended for type 2 diabetes (T2D) treatment. The impact of diet in shaping the gut microbiota is well known, particularly for MD. However, the link between MD and diabetes outcome improvement is not completely clear. This study aims to evaluate the role of microbiota modulation by a nonpharmacological intervention in patients with T2D. In this 12-week single-arm pilot study, nine participants received individual nutritional counseling sessions promoting MD. Gut microbiota, biochemical parameters, body composition, and blood pressure were assessed at baseline, 4 weeks, and 12 weeks after the intervention. Adherence to MD [assessed by Mediterranean Diet Adherence Screener (MEDAS) score] increased after the intervention. Bacterial richness increased after 4 weeks of intervention and was negatively correlated with fasting glucose levels and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR). Prevotella to Bacteroides ratio also increased after 4 weeks. In contrast, glycated haemoglobin (HbA1c) and HOMA-IR were only decreased at the end of study. Alkaline phosphatase activity was assessed in fecal samples and was negatively correlated with HbA1c and positively correlated with bacterial diversity. The results of this study reinforce that MD adherence results in a better glycemic control in subjects with T2D. Changes in gut bacterial richness caused by MD adherence may be relevant in mediating the metabolic impact of this dietary intervention.


Assuntos
Diabetes Mellitus Tipo 2/dietoterapia , Diabetes Mellitus Tipo 2/metabolismo , Dieta Mediterrânea , Microbioma Gastrointestinal , Idoso , Fosfatase Alcalina/metabolismo , Bacteroides/fisiologia , Biodiversidade , Pressão Sanguínea , Composição Corporal , Diabetes Mellitus Tipo 2/microbiologia , Diabetes Mellitus Tipo 2/fisiopatologia , Fezes/microbiologia , Comportamento Alimentar , Feminino , Alimentos , Hemoglobina A Glicada/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Cooperação do Paciente , Projetos Piloto , Prevotella/fisiologia , Inquéritos e Questionários
16.
Nutr Metab Cardiovasc Dis ; 31(5): 1454-1466, 2021 05 06.
Artigo em Inglês | MEDLINE | ID: mdl-33810955

RESUMO

BACKGROUND AND AIMS: Host-microbiota interactions involving metabolic pathways have been linked to the pathogenesis of atherosclerotic disease and type 2 diabetes. As stable coronary artery disease (SCAD) patients combined with type 2 diabetes have significantly increased risk for cardiac event, we focused on elucidating the role of microbiota affecting cardiometabolic disease development. METHODS AND RESULTS: We used multi-omics analyses (metagenomics and metabolomics) of fecal and serum samples from a prospective cohort including stable coronary artery disease combined with diabetes mellitus (SCAD + T2DM, n = 38), SCAD (n = 71), and healthy control (HC, n = 55). We linked microbiome features to disease severity in a three-pronged association analysis and identified prognostic bacterial biomarkers. We identified that bacterial and metabolic signatures varied significantly between SCAD and SCAD + T2DM groups. SCAD + T2DM individuals were characterized by increased levels of aromatic amino acids and carbohydrates, which correlate with a gut microbiome with enriched biosynthetic potential. Our study also addressed how metformin may confound gut dysbiosis and increase the potential for nitrogen metabolism. In addition, we found that specific bacterial taxa Ruminococcus torques [HR: 2.363 (08-4.56), P = 0.03] was predictive of cardiac survival outcomes. CONCLUSION: Overall, our study identified relationships between features of the gut microbiota (GM) and circulating metabolites, providing a new direction for future studies aiming to understand the host-GM interplay in atherosclerotic cardiovascular pathogenesis.


Assuntos
Bactérias/metabolismo , Doença da Artéria Coronariana/microbiologia , Diabetes Mellitus Tipo 2/microbiologia , Microbioma Gastrointestinal , Intestinos/microbiologia , Idoso , Bactérias/efeitos dos fármacos , Bactérias/crescimento & desenvolvimento , Biomarcadores/sangue , Estudos de Casos e Controles , Clostridiales/crescimento & desenvolvimento , Clostridiales/metabolismo , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/diagnóstico , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Disbiose , Feminino , Microbioma Gastrointestinal/efeitos dos fármacos , Interações Hospedeiro-Patógeno , Humanos , Hipoglicemiantes/uso terapêutico , Masculino , Metabolômica , Metagenômica , Metformina/uso terapêutico , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos
17.
Int J Mol Sci ; 22(7)2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33808194

RESUMO

Metformin is the first-line pharmacotherapy for treating type 2 diabetes mellitus (T2DM); however, its mechanism of modulating glucose metabolism is elusive. Recent advances have identified the gut as a potential target of metformin. As patients with metabolic disorders exhibit dysbiosis, the gut microbiome has garnered interest as a potential target for metabolic disease. Henceforth, studies have focused on unraveling the relationship of metabolic disorders with the human gut microbiome. According to various metagenome studies, gut dysbiosis is evident in T2DM patients. Besides this, alterations in the gut microbiome were also observed in the metformin-treated T2DM patients compared to the non-treated T2DM patients. Thus, several studies on rodents have suggested potential mechanisms interacting with the gut microbiome, including regulation of glucose metabolism, an increase in short-chain fatty acids, strengthening intestinal permeability against lipopolysaccharides, modulating the immune response, and interaction with bile acids. Furthermore, human studies have demonstrated evidence substantiating the hypotheses based on rodent studies. This review discusses the current knowledge of how metformin modulates T2DM with respect to the gut microbiome and discusses the prospect of harnessing this mechanism in treating T2DM.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/microbiologia , Microbioma Gastrointestinal/fisiologia , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Ácidos e Sais Biliares/metabolismo , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/imunologia , Ácidos Graxos Voláteis/metabolismo , Microbioma Gastrointestinal/efeitos dos fármacos , Humanos , Hipoglicemiantes/farmacologia , Metformina/farmacologia
18.
Nutr Res ; 89: 10-22, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33878569

RESUMO

The health benefits of carefully restricting the energy intake in a strategic manner whilst avoiding malnutrition are widely discussed. In the recent years, the great impact of the gut microbiota on its host has been clarified more and more. Since the gut microbiota produces a number of metabolites and molecules that can affect host metabolism, modulating it with dietary restriction can influence the health and the progression of disease of its host on various levels. This review comprises 15 studies investigating the effect of different variants of fasting and caloric restriction on the gastrointestinal microbiome and its metabolites. The data suggest that changing the gut microbiota composition by dietary restriction has the potential to positively influence the progression of several diseases such as obesity, diabetes, neurological diseases or inflammatory bowel disease. Finally, the relevance of the findings for clinical practice is evaluated and approaches for future research are proposed.


Assuntos
Restrição Calórica , Microbioma Gastrointestinal , Trato Gastrointestinal/microbiologia , Tecido Adiposo/fisiologia , Animais , Encéfalo/metabolismo , Doenças do Sistema Nervoso Central/dietoterapia , Doenças do Sistema Nervoso Central/microbiologia , Colo/microbiologia , Colo/fisiologia , Diabetes Mellitus Tipo 2/dietoterapia , Diabetes Mellitus Tipo 2/microbiologia , Progressão da Doença , Feminino , Humanos , Doenças Inflamatórias Intestinais/dietoterapia , Doenças Inflamatórias Intestinais/microbiologia , Masculino , Obesidade/dietoterapia , Obesidade/microbiologia
19.
Int J Food Sci Nutr ; 72(8): 1083-1094, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33870850

RESUMO

In vitro digestion of curdlan oligosaccharides (COSs), pullulan oligosaccharides (POSs), xanthan gum oligosaccharides (XGOSs) and gellan gum oligosaccharides (GGOSs) was investigated. These four oligosaccharides showed resistance to simulated saliva and gastric and small intestinal fluid. In further fermentation with faecal microbiota from healthy subjects and type 2 diabetes (T2D) patients, COS fermentation significantly increased the abundance of Bifidobacterium spp. and Lactobacillus spp. and the production of short-chain fatty acids in healthy and T2D groups. Digestion of XGOS enhanced the growth of the Clostridium leptum subgroup and significantly increased butyric acid production in healthy and T2D groups. Sole fermentation with COS, POS, XGOS and GGOS exhibited different metabolic profiles between healthy and T2D groups, and more small molecule polyols were produced in the T2D group than in the healthy group. This study provides a novel perspective on the reconstruction of gut microbiota and metabolism by POS, COS, GGOS and XGOS intervention.


Assuntos
Diabetes Mellitus Tipo 2 , Microbioma Gastrointestinal , Metaboloma , Oligossacarídeos/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/microbiologia , Ácidos Graxos Voláteis , Fezes/microbiologia , Fermentação , Humanos
20.
Acta Diabetol ; 58(7): 881-897, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33723651

RESUMO

AIMS: Liraglutide controls type 2 diabetes (T2D) and inflammation. Gut microbiota regulates the immune system and causes at least in part type 2 diabetes. We here evaluated whether liraglutide regulates T2D through both gut microbiota and immunity in dysmetabolic mice. METHODS: Diet-induced dysmetabolic mice were treated for 14 days with intraperitoneal injection of liraglutide (100 µg/kg) or with vehicle or Exendin 4 (10 µg/kg) as controls. Various metabolic parameters, the intestinal immune cells were characterized and the 16SrDNA gene sequenced from the gut. The causal role of gut microbiota was shown using large spectrum antibiotics and by colonization of germ-free mice with the gut microbiota from treated mice. RESULTS: Besides, the expected metabolic impacts liraglutide treatment induced a specific gut microbiota specific signature when compared to vehicle or Ex4-treated mice. However, liraglutide only increased glucose-induced insulin secretion, reduced the frequency of Th1 lymphocytes, and increased that of TReg in the intestine. These effects were abolished by a concomitant antibiotic treatment. Colonization of germ-free mice with gut microbiota from liraglutide-treated diabetic mice improved glucose-induced insulin secretion and regulated the intestinal immune system differently from what observed in germ-free mice colonized with microbiota from non-treated diabetic mice. CONCLUSIONS: Altogether, our result demonstrated first the influence of liraglutide on gut microbiota and the intestinal immune system which could at least in part control glucose-induced insulin secretion.


Assuntos
Microbioma Gastrointestinal/efeitos dos fármacos , Sistema Imunitário/efeitos dos fármacos , Secreção de Insulina/efeitos dos fármacos , Mucosa Intestinal/efeitos dos fármacos , Liraglutida/farmacologia , Animais , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/imunologia , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/microbiologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/imunologia , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/microbiologia , Mucosa Intestinal/imunologia , Mucosa Intestinal/microbiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL
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