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1.
Food Chem Toxicol ; 135: 110886, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31626838

RESUMO

Diabetes mellitus has become a worldwide concern in recent years. In this study, the effect of Holothuria leucospilota polysaccharide (HLP) on type 2 diabetes mellitus (T2DM) was investigated in Goto-Kakizaki (GK) rats. The results showed that HLP significantly improved glucose intolerance and regulated blood lipid and hormone levels (p < 0.05). Pathological analysis showed that HLP repaired the impairments of the pancreas and colon in diabetic rats. In addition, a high dose of HLP (200 mg/kg) significantly upregulated the gene expression of peroxisome proliferator-activated receptor-α (PPAR-α), peroxisome proliferator-activated receptor-γ (PPAR-γ), phosphoinositide 3-kinase (PI3K), protein kinase B (PKB/AKT), glucose transporter-4 (GLUT4) and anti-apoptotic (Bcl-2), and downregulated the mRNA levels of pro-apoptotic (Bax) and cluster of differentiation 36 (CD36) in diabetic rats (p < 0.05). Furthermore, HLP treatment increased the short-chain fatty acid-producing bacteria and decreased the opportunistic bacterial pathogen in the feces of diabetic rats. These results demonstrated that HLP has the potential to ameliorate T2DM in GK rats.


Assuntos
Diabetes Mellitus Experimental/microbiologia , Diabetes Mellitus Tipo 2/microbiologia , Microbioma Gastrointestinal/efeitos dos fármacos , Polissacarídeos/farmacologia , Adiponectina/metabolismo , Animais , Glicemia/metabolismo , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Tipo 2/sangue , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Insulina/metabolismo , Leptina/metabolismo , Lipídeos/sangue , Masculino , Receptores Ativados por Proliferador de Peroxissomo/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Pepinos-do-Mar , Transdução de Sinais
2.
PLoS Pathog ; 15(12): e1008140, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31809521

RESUMO

Previously, we found that pathological immune responses enhance the mortality rate of Mycobacterium tuberculosis (Mtb)-infected mice with type 2 diabetes mellitus (T2DM). In the current study, we evaluated the role of the cytokine IL-22 (known to play a protective role in bacterial infections) and type 3 innate lymphoid cells (ILC3s) in regulating inflammation and mortality in Mtb-infected T2DM mice. IL-22 levels were significantly lower in Mtb-infected T2DM mice than in nondiabetic Mtb-infected mice. Similarly, serum IL-22 levels were significantly lower in tuberculosis (TB) patients with T2DM than in TB patients without T2DM. ILC3s were an important source of IL-22 in mice infected with Mtb, and recombinant IL-22 treatment or adoptive transfer of ILC3s prolonged the survival of Mtb-infected T2DM mice. Recombinant IL-22 treatment reduced serum insulin levels and improved lipid metabolism. Recombinant IL-22 treatment or ILC3 transfer prevented neutrophil accumulation near alveoli, inhibited neutrophil elastase 2 (ELA2) production and prevented epithelial cell damage, identifying a novel mechanism for IL-22 and ILC3-mediated inhibition of inflammation in T2DM mice infected with an intracellular pathogen. Our findings suggest that the IL-22 pathway may be a novel target for therapeutic intervention in T2DM patients with active TB disease.


Assuntos
Diabetes Mellitus Tipo 2/imunologia , Diabetes Mellitus Tipo 2/microbiologia , Interleucinas/imunologia , Linfócitos/imunologia , Tuberculose/imunologia , Animais , Diabetes Mellitus Tipo 2/complicações , Humanos , Imunidade Inata/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Mycobacterium tuberculosis/imunologia , Tuberculose/complicações
3.
Medicine (Baltimore) ; 98(44): e17786, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31689851

RESUMO

RATIONALE: Grade 4 diabetic foot (DF) is a severe infection that causes bone destruction, osteomyelitis, and osteoarticular damage, which, in turn, can lead to serious dry or wet gangrene, or amputation. DF is extremely difficult to treat. PATIENT CONCERNS: A 71-year-old female patient with long-term diabetes complicated with uremia, who undergoes regular hemodialysis 2 to 3 times per week, was admitted with grade 4 DF with Pseudomonas aeruginosa infection, and concomitant vascular occlusion of the lower extremities. The patient had a concurrent nutrition and electrolyte disorder. DIAGNOSES: The patient was diagnosed with type 2 diabetes, grade 4 DF, postamputation of the 2nd toe, vascular occlusion of the lower extremities, atherosclerosis, uremia, hypoproteinemia, and electrolyte disturbances. INTERVENTIONS: Treatment with antibiotics and comprehensive measures aimed at improving nutrition and microcirculation, controlling blood glucose, as well as balancing electrolytes were performed to ameliorate the general conditions. Nibbled debridement was used to remove devitalized tissues each time to maintain as much vital cells as possible. Open therapy was used for necrotic tissues, and dressings therapy was used simultaneously for the infected lesion. This combined treatment, involving open therapy with dressing, is referred to as "semiclosure wound therapy." Negative pressure wound therapy (NPWT) was used after a fistula formed. OUTCOMES: During the treatment procedure, the gangrene 3rd toe was spontaneously shed; the necrotic 1st toe was removed by surgery. The wound gradually healed after 3 months of open therapy combined with dressing. High location amputation was avoided. LESSONS: Semiclosure, which constitutes open therapy combined with the use of dressings, plus NPWT can preserve vital skin cells in the wound and control the aggravation of the infection. It is an effective and novel measure that prevents DF amputation in old patient and promotes wound union.


Assuntos
Desbridamento/métodos , Diabetes Mellitus Tipo 2/complicações , Pé Diabético/terapia , Tratamento de Ferimentos com Pressão Negativa/métodos , Doenças Vasculares Periféricas/terapia , Infecções por Pseudomonas/terapia , Pseudomonas aeruginosa , Idoso , Antibacterianos/uso terapêutico , Bandagens , Terapia Combinada , Diabetes Mellitus Tipo 2/microbiologia , Feminino , Humanos , Doenças Vasculares Periféricas/microbiologia , Infecções por Pseudomonas/microbiologia
4.
Curr Med Sci ; 39(5): 679-684, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31612382

RESUMO

Diet has been shown to play an important role in human physiology. It is a predominant exogenous factor regulating the composition of gut microbiota, and dietary intervention holds promise for treatment of diseases such as obesity, type 2 diabetes, and malnutrition. Furthermore, it was reported that diet has significant effects on physiological processes of C. elegans, including reproduction, fat storage, and aging. To reveal novel signaling pathways responsive to different diets, C. elegans and its bacterial diet were used as an interspecies model system to mimic the interaction between host and gut microbiota. Most signaling pathways identified in C. elegans are highly conserved across different species, including humans. A better understanding of these pathways can, therefore, help to develop interventions for human diseases. In this article, we summarize recent achievements on molecular mechanisms underlying the response of C. elegans to different diets and discuss their relevance to human health.


Assuntos
Envelhecimento/genética , Caenorhabditis elegans/fisiologia , Escherichia coli/genética , Microbioma Gastrointestinal/fisiologia , Redes e Vias Metabólicas/genética , Animais , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/microbiologia , Dieta/métodos , Modelos Animais de Doenças , Escherichia coli/química , Escherichia coli/metabolismo , Humanos , Desnutrição/genética , Desnutrição/metabolismo , Desnutrição/microbiologia , Obesidade/genética , Obesidade/metabolismo , Obesidade/microbiologia , Interferência de RNA , RNA Bacteriano/antagonistas & inibidores , RNA Bacteriano/genética , RNA Bacteriano/metabolismo , Reprodução/genética , Transdução de Sinais
5.
Orv Hetil ; 160(41): 1623-1632, 2019 Oct.
Artigo em Húngaro | MEDLINE | ID: mdl-31587580

RESUMO

Introduction: Previous data showed bacterial infections among diabetic patients to be more serious and frequent, with higher mortality rates in comparison with non-diabetics. Recent investigations, however, are contradictory. Aim: The goal of our prospective, observational study was to compare patients hospitalized on a general medical ward due to community-acquired bacterial infections with type 2 diabetes mellitus (T2DM) to those of non-diabetics (K) by 1) infection localization, 2) spectrum of pathogens, 3) three-month mortality rates. Method: Patients were consecutively involved (T2DM: n = 205, K: n = 202). We characterized the infections, clinical parameters, mortalities of the two groups, and matched them to international data. Results: No difference regarding clinical details of the groups were found except for glycemic parameters and BMI. In the T2DM group the skin- and soft tissue- (37.1%), in the K patients respiratory infections (37.1%) were the most common, followed by urinary ones (31.2% and 31.7%, respectively). Skin- and soft tissue infection incidence among T2DM subjects were higher compared to international results (37.1% vs. 16%). Co-presence of Gram positive and Gram negative bacteria in the skin- and soft tissue infections (23/76 vs. 5/46, p = 0.0149), and polymicrobial origin in the urinary tract infections (34.0% vs. 15.1%, p = 0.0335) were found to be more frequent in T2DM than in K. No difference regarding mortality rates were detected. In T2DM the skin- and soft tissue while in the K group the respiratory infections had the most death counts. Conclusions: We found higher rates of skin- and soft tissue infections among T2DM patients hospitalized on a general medical ward compared to international data. In total we did not find difference regarding three-month mortality between the groups. Our results highlight the importance of primary prevention and shows its inadequacy concerning skin and soft tissue infections among type 2 diabetics in Hungary. Orv Hetil. 2019; 160(41): 1623-1632.


Assuntos
Infecções Bacterianas/diagnóstico , Infecções Comunitárias Adquiridas/microbiologia , Diabetes Mellitus Tipo 2/complicações , Bactérias Gram-Negativas/isolamento & purificação , Bactérias Gram-Positivas/isolamento & purificação , Infecções dos Tecidos Moles/microbiologia , Infecções Urinárias/microbiologia , Adulto , Idoso , Infecções Bacterianas/epidemiologia , Infecções Comunitárias Adquiridas/epidemiologia , Diabetes Mellitus Tipo 2/microbiologia , Feminino , Humanos , Hungria/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Infecções dos Tecidos Moles/epidemiologia , Infecções Urinárias/epidemiologia
6.
J Physiol Pharmacol ; 70(3)2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31539885

RESUMO

The presence of type 2 diabetes mellitus (DM) in patients with cirrhosis is associated with an increased risk of spontaneous bacterial peritonitis (SBP) which may represent an increased susceptibility to infections. Endocan is a key player in the regulation of inflammatory disorders, and a biomarker in bacteremia and sepsis. To investigate the association between both endocan and DM, and developing SBP, we conducted a retrospective cohort study. Three hundred and thirty patients (179 men, 151 women; mean age 61.0 ± 8.5 years) who were treated for liver cirrhosis were studied between January 2007 and December 2016. Univariate and multivariate analyses using age, type 2 diabetes mellitus, severity of cirrhosis (Child-Pugh or MELD score), platelet count, serum proinflammatory cytokines, procalcitonin, C-reactive protein, and endocan level were conducted to identify factors related to the development of SBP. Among 330 patients with the median follow-up of 6.0 years, the cumulative incidence of SBP at 5 years was 28.6%. On multivariate analysis, a high serum endocan level and DM were independent and significant risk factors for SBP development (hazard ratio (HR) 1.634 (95% CI: 1.012 - 2.638; P = 0.047) and 2.482 (95% CI: 1.134 - 5.412; P = 0.023), respectively). Furthermore, the cumulative incidence rate of SBP in cirrhotic patients with high endocan levels was significantly greater than that in patients with low endocan levels (P = 0.035; log-rank test). Endocan is an independent predictor of SBP development in patients with cirrhosis. Cirrhotic patients with type 2 diabetes mellitus who have a higher endocan levels should be monitored carefully for the development of spontaneous bacterial peritonitis.


Assuntos
Infecções Bacterianas/microbiologia , Diabetes Mellitus Tipo 2/sangue , Cirrose Hepática/sangue , Cirrose Hepática/microbiologia , Proteínas de Neoplasias/sangue , Peritonite/sangue , Peritonite/microbiologia , Proteoglicanas/sangue , Idoso , Infecções Bacterianas/sangue , Infecções Bacterianas/metabolismo , Biomarcadores/sangue , Biomarcadores/metabolismo , Citocinas/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/microbiologia , Feminino , Humanos , Inflamação/sangue , Inflamação/metabolismo , Cirrose Hepática/metabolismo , Masculino , Pessoa de Meia-Idade , Peritonite/metabolismo , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença
7.
Artigo em Inglês | MEDLINE | ID: mdl-31480468

RESUMO

BACKGROUND: Type-2-Diabetes (T2D) and Periodontitis are major inflammatory diseases. However, not much is known about the specific subgingival microbiota in Mexicans with diabetes and metabolic dysbiosis. The aim of this study was to describe the subgingival microbiota of Mexicans with T2D and the different periodontal and metabolic conditions, through "Checkerboard" DNA-DNA hybridization. METHODS: Subjects were divided into two groups-periodontal-health (PH) (PH_non-T2D; n = 59, PH_T2D; n = 14) and generalized-periodontitis (GP) (GP_non-T2D; n = 67, GP_T2D; n = 38). Obesity (BMI ≥ 30 kg/m2) and serum levels of glycated-hemoglobin (HbA1c), total-lipids, triglycerides, total-cholesterol, high-density-lipids, and low-density-lipids were measured for the T2D individuals. Subgingival microbial identification was processed for 40 species through DNA-probes. RESULTS: Subjects with T2D harbored significantly higher mean total levels (PH: p < 0.001, and GP_NS), a lower proportion of "red" complex (GP: p < 0.01), a higher proportion of "yellow" (GP; p < 0.001), and "orange" (GP; p < 0.01) complex than the non-T2D. GP_T2D individuals exhibited a greater proportion of putative-species-Campylobacter gracilis and S. constellatus (p < 0.001), and Parvimonas micra and Prevotella nigrescens (p < 0.01), than GP_non-T2D. T2D individuals with HbA1c > 8% had presented significantly higher mean pocket-depth and higher levels of G. morbillorum (p < 0.05) and those with obesity or dyslipidemia harbored higher levels, prevalence, or proportion of Streptococcus sp., Actinomyces sp., and Capnocytophaga sp. CONCLUSIONS: T2D individuals harbored a particular microbial profile different to non-T2D microbiota. Metabolic control was related to dysbiosis of microbiota-HbA1c>8% related to periodontitis and obesity or dyslipidemia with the predominance of saccharolytic bacteria, irrespective of their periodontal condition.


Assuntos
Bactérias/isolamento & purificação , Diabetes Mellitus Tipo 2/microbiologia , Doenças da Gengiva/microbiologia , Microbiota , Periodontite/microbiologia , Adulto , Bactérias/genética , Campylobacter/genética , Feminino , Humanos , Masculino , México , Pessoa de Meia-Idade , Hibridização de Ácido Nucleico
8.
Biomed Pharmacother ; 118: 109131, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31545226

RESUMO

Berberine and metformin, both established pharmaceutical agents with herbal origins, have incidental beneficial effects on multiple diseases, including diabetes. These effects have been speculated to occur via the gut microbiome. In this study, we administered either berberine or metformin to db/db mice and investigated changes in body weight, food intake, and blood glucose levels. Fresh stool samples were analyzed using 16 s rDNA high-throughput sequencing to evaluate the gut microbiome. Short-chain fatty acids (SCFA) in the stool were quantified using gas chromatography. The expression of NF-κB signaling pathway and tight junction (ZO1 and occludin) proteins in the intestinal epithelium was determined using qPCR and western blotting. The intestinal barrier structure was examined using transmission electron microscopy and serum lipopolysaccharide (LPS) was measured using a commercial kit. Both berberine and metformin reduced food intake, body weight, and blood glucose and HbA1c levels. Both treatments effectively restored the intestinal SCFA content, reduced the level of serum LPS, relieved intestinal inflammation, and repaired intestinal barrier structure. Intervention with metformin or berberine modified the gut microbiome in db/db mice, increasing the number of SCFA-producing bacteria (e.g., Butyricimonas, Coprococcus, Ruminococcus) and reducing opportunistic pathogens (e.g., Prevotella, Proteus). An increased abundance of other probiotics including Lactobacillus and Akkermansia was also observed. Berberine and metformin can modulate the composition of the gut microbiome and reduce body weight, blood glucose levels, and intestinal inflammation in db/db mice, which demonstrates their effectiveness in the reduction of diabetic complications in this model.


Assuntos
Berberina/farmacologia , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Gastroenterite/prevenção & controle , Microbioma Gastrointestinal/efeitos dos fármacos , Hipoglicemiantes/farmacologia , Metformina/farmacologia , Animais , Glicemia/análise , Peso Corporal/efeitos dos fármacos , Diabetes Mellitus Experimental/imunologia , Diabetes Mellitus Experimental/microbiologia , Diabetes Mellitus Tipo 2/imunologia , Diabetes Mellitus Tipo 2/microbiologia , Ingestão de Alimentos/efeitos dos fármacos , Gastroenterite/microbiologia , Hemoglobina A Glicada/análise , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/imunologia , Mucosa Intestinal/microbiologia , Obesidade/imunologia , Obesidade/microbiologia , Obesidade/prevenção & controle , Permeabilidade
9.
Nutrients ; 11(8)2019 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-31409000

RESUMO

Helicobacter pylori (H. pylori) may be involved in diabetes and other insulin-related processes. This study aimed to investigate the associations between H. pylori infection and the risks of type 2 diabetes, impaired glucose tolerance (IGT), diabetic nephropathy, and poor glycemic control. We retrospectively evaluated 16,091 subjects without diabetes at baseline who underwent repeated health examinations. Subjects were categorized according to whether they were seropositive and seronegative for H. pylori infection. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazard models. The serological results were validated using an independent cohort (n = 42,351) based on a histological diagnosis of H. pylori infection. During 108,614 person-years of follow-up, 1338 subjects (8.3%) developed newly diagnosed diabetes, although the cumulative incidence of diabetes was not significantly related to serological H. pylori status. The multivariate Cox proportional-hazards regression models revealed that H. pylori seropositivity was not significantly associated with diabetes (HR: 1.01, 95% CI: 0.88-1.16; p = 0.854), IGT (HR: 0.98, 95% CI: 0.93-1.04; p = 0.566), diabetic nephropathy (HR: 0.99, 95% CI: 0.82-1.21; p = 0.952), or poor glycemic control (HR: 1.05, 95% CI: 0.90-1.22; p = 0.535). Similarly, histopathological findings of H. pylori infection were not significantly associated with diabetes (p = 0.311), diabetic nephropathy (p = 0.888), or poor glycemic control (p = 0.989). The findings from these large Korean cohorts indicate that there does not appear to be a role for past H. pylori infection in the development of diabetes, IGT, diabetic nephropathy, or poor glycemic control.


Assuntos
Diabetes Mellitus Tipo 2 , Infecções por Helicobacter , Helicobacter pylori/crescimento & desenvolvimento , Glicemia/metabolismo , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/etiologia , Diabetes Mellitus Tipo 2/microbiologia , Nefropatias Diabéticas/etiologia , Feminino , Intolerância à Glucose/etiologia , Infecções por Helicobacter/complicações , Infecções por Helicobacter/microbiologia , Infecções por Helicobacter/patologia , Humanos , Hiperglicemia/etiologia , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , República da Coreia , Estudos Retrospectivos , Fatores de Risco
10.
BMC Urol ; 19(1): 78, 2019 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-31438919

RESUMO

BACKGROUND: Lower urinary tract symptoms (LUTS) is the most common complication of diabetes. However, the underlying pathogenesis of cultured negative LUTS (cn-LUTS) in diabetic patients has not been well understood. Numerous evidence indicates that urinary dysbiosis is related to urologic disorders. We aim to study alterations of the urinary microbiota of cn-LUTS in type 2 diabetes (T2D) patients. METHODS: Female T2D patients and controls were recruited and requested to finish the American Urological Association Symptom Index. Mid-stream urine was collected for culturing and extracting DNA. Microbial diversity and composition were analyzed by targeting to 16S rDNA. Linear discriminant analysis effect size (LEfSe) was carried out to identify significantly different bacteria. RESULTS: 32 female T2D patients and 26 controls were enrolled. No significant differences in alpha diversity were observed between patients and controls. However, statistically decreased richness (ACE index and Chao 1 index, 85.52(13.75, 204.84) vs. 129.82(63.89, 280.30) and 83.86(11.00, 210.77) vs. 125.19(62.00, 251.77), P = 0.005; Observed Species, 76(10, 175) vs. 98(54, 234), P = 0.011) and decreased species diversity (Shannon index, 1.37(0.04, 3.48) vs. 2.09(0.98, 3.43), P = 0.033; Simpson index, 0.46 (0.06, 0.99) vs. 0.23(0.07, 0.64), P = 0.029) were shown in moderate-to-severe LUTS group and high Hemoglobin A1c group, respectively. A significant difference of beta diversity was found between T2D patients and controls and T2D patients with different severity of cn-LUTS as well as the different level of Hemoglobin A1c. LEfSe revealed that 10 genera (e.g., Escherichia-Shigella and Klebsiella) were increased and 7 genera were decreasing in T2D patients, 3 genera (e.g., Escherichia-Shigella and Campylobacter) were increased and 16 genera (e.g., Prevotella) were reduced in moderate-to-severe LUTS group, 2 genera (Escherichia-Shigella and Lactobacillus) were over-represented and 10 genera (e.g., Prevotella) were under-represented in high Hemoglobin A1c group. Finally, Hemoglobin A1c was found positively correlated with the total score of the American Urological Association Symptom Index (r = 0.509, P = 0.003). CONCLUSIONS: Urinary dysbiosis may be related to cn-LUTS in female T2D patients. A better understanding of urinary microbiota in the development and progression of cn-LUTS in female T2D patients was necessary. The severity of cn-LUTS was correlated to hyperglycemia and chronic hyperglycemia might induce or promote cn-LUTS by influencing urinary microbiota.


Assuntos
Complicações do Diabetes/microbiologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/microbiologia , Sintomas do Trato Urinário Inferior/etiologia , Sintomas do Trato Urinário Inferior/microbiologia , Microbiota , Idoso , Estudos Transversais , Feminino , Humanos , Pessoa de Meia-Idade
11.
Food Funct ; 10(9): 5804-5815, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31461095

RESUMO

Diabetes, an endocrine and metabolic disorder, has become the third most non-infectious chronic disease that threatens human health. Type 2 diabetes (T2D) accounts for more than 90% of diabetic patients, mainly caused by environmental factors. Lactic acid bacteria (LAB) exhibit several health benefits to the host including regulating glucose and lipid metabolism and improving oxidative stress and inflammatory response. However, the anti-diabetic mechanism of probiotics has not been elucidated clearly. In this study, the anti-diabetic effects of Lactobacillus acidophilus KLDS1.1003 and KLDS1.0901 on T2D mice were assessed. Oral administration of L. acidophilus KLDS1.1003 and KLDS1.0901 for 6 weeks significantly improved the epithelial barrier function, which in turn lowered inflammation cytokines, including IL-8, TNF-α and IL-1ß in liver and colon tissue, and prevented liver and colon tissue injuries to some extent. Additionally, L. acidophilus treatment regulated the expression genes that are related to glucose and lipid metabolism. The two tested strains down-regulated the expression of glycogen synthase kinase 3ß (GSK-3ß), fatty acid synthase (FAS) and sterol regulatory element-binding transcription factor 1c (SREBP-1c), and up-regulated the expression of protein kinase B (Akt). However, L. acidophilus KLDS1.0901 is better for improving T2D than L. acidophilus KLDS1.1003. Further research showed that L. acidophilus KLDS1.0901 supplementation could reshape gut microbiota, increasing short chain fatty acid-producing bacteria (Blautia, Roseburia and Anaerotruncus) and the level of SCFAs and decreasing the relative abundance of Gram-negative bacteria such as Desulfovibrio, Alistipes and Bacteroides. Notably, L. acidophilus KLDS1.0901 treatment restored the structure of gut microbiota similar to the control group. These findings suggested that L. acidophilus KLDS1.0901 might be used as a new type of antidiabetic drug candidate.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Microbioma Gastrointestinal/efeitos dos fármacos , Glucose/metabolismo , Hipoglicemiantes/administração & dosagem , Lactobacillus acidophilus/fisiologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/metabolismo , Probióticos/administração & dosagem , Animais , Bactérias/classificação , Bactérias/efeitos dos fármacos , Bactérias/genética , Bactérias/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/microbiologia , Ácido Graxo Sintases/genética , Ácido Graxo Sintases/metabolismo , Ácidos Graxos Voláteis/metabolismo , Glicogênio Sintase Quinase 3 beta/genética , Glicogênio Sintase Quinase 3 beta/metabolismo , Humanos , Fígado/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo
12.
Nutrients ; 11(7)2019 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-31261830

RESUMO

Gut microbiota dysbiosis has been recognized as having key importance in obesity- and metabolic-related diseases. Although there is increasing evidence of the potential benefits induced by probiotics in metabolic disturbances, there is a lack of large cross-sectional studies to assess population-based prevalence of probiotic intake and metabolic diseases. Our aim was to evaluate the association of probiotic ingestion with obesity, type 2 diabetes, hypertension, and dyslipidemia. A cross-sectional study was designed using data from the National Health and Nutrition Examination Survey (NHANES), 1999-2014. Probiotic ingestion was considered when a subject reported consumption of yogurt or a probiotic supplement during the 24-hour dietary recall or during the Dietary Supplement Use 30-Day questionnaire. We included 38,802 adults and 13.1% reported probiotic ingestion. The prevalence of obesity and hypertension was lower in the probiotic group (obesity-adjusted Odds Ratio (OR): 0.84, 95% CI 0.76-0.92, p < 0.001; hypertension-adjusted OR: 0.79, 95% CI 0.71-0.88, p < 0.001). Accordingly, even after analytic adjustments, body mass index (BMI) was significantly lower in the probiotic group, as were systolic and diastolic blood pressure and triglycerides; high-density lipoprotein (HDL) was significantly higher in the probiotic group for the adjusted model. In this large-scale study, ingestion of probiotic supplements or yogurt was associated with a lower prevalence of obesity and hypertension.


Assuntos
Diabetes Mellitus Tipo 2/prevenção & controle , Dislipidemias/prevenção & controle , Microbioma Gastrointestinal , Trato Gastrointestinal/microbiologia , Hipertensão/prevenção & controle , Obesidade/prevenção & controle , Probióticos/administração & dosagem , Iogurte/microbiologia , Adulto , Estudos Transversais , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/microbiologia , Disbiose , Dislipidemias/diagnóstico , Dislipidemias/epidemiologia , Dislipidemias/microbiologia , Feminino , Humanos , Hipertensão/diagnóstico , Hipertensão/epidemiologia , Hipertensão/microbiologia , Masculino , Pessoa de Meia-Idade , Obesidade/diagnóstico , Obesidade/epidemiologia , Obesidade/microbiologia , Prevalência , Fatores de Proteção , Medição de Risco , Fatores de Risco , Estados Unidos/epidemiologia
13.
Biomed Pharmacother ; 117: 109138, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31247468

RESUMO

Type 2 diabetes mellitus (T2DM) is a common clinical chronic disease, while its pathogenesis is still inconclusive. Intestinal flora, the largest micro-ecological system in the human body, is involved in, meanwhile has a major impact on the body's material and energy metabolism. Recent studies have shown that in addition to obesity, genetics, and islet dysfunction, the disturbance of intestinal flora may partly give rise to diabetes. In this paper, we summarized the current research on the correlation between T2DM and intestinal flora, and concluded the pathological mechanisms of intestinal flora involved in T2DM. Moreover, the ideas and methods of prevention and treatment of T2DM based on intestinal flora were proposed, providing theoretical basis and literature reference for the treatment of T2DM and its complications based on the regulation of intestinal flora.


Assuntos
Pesquisa Biomédica , Diabetes Mellitus Tipo 2/microbiologia , Microbioma Gastrointestinal , Diabetes Mellitus Tipo 2/prevenção & controle , Diabetes Mellitus Tipo 2/terapia , Ácidos Graxos/metabolismo , Transplante de Microbiota Fecal , Humanos , Modelos Biológicos
14.
Arch Oral Biol ; 104: 13-23, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31153098

RESUMO

OBJECTIVE: The aim of this study was to use high-resolution whole metagenomic shotgun sequencing to characterize the subgingival microbiome of patients with/without type 2 Diabetes Mellitus and with/without periodontitis. DESIGN: Twelve subjects, falling into one of the four study groups based on the presence/absence of poorly controlled type 2 Diabetes Mellitus and moderate-severe periodontitis, were selected. For each eligible subject, subgingival plaque samples were collected at 4 sites, all representative of the periodontal condition of the individual (i.e., non-bleeding sulci in subjects without a history of periodontitis, bleeding pockets in patients with moderate-severe periodontitis). The subgingival microbiome was evaluated using high-resolution whole metagenomic shotgun sequencing. RESULTS: The results showed that: (i) the presence of type 2 Diabetes Mellitus and/or periodontitis were associated with a tendency of the subgingival microbiome to decrease in richness and diversity; (ii) the presence of type 2 Diabetes Mellitus was not associated with significant differences in the relative abundance of one or more species in patients either with or without periodontitis; (iii) the presence of periodontitis was associated with a significantly higher relative abundance of Anaerolineaceae bacterium oral taxon 439 in type 2 Diabetes Mellitus patients. CONCLUSIONS: Whole metagenomic shotgun sequencing of the subgingival microbiome was extremely effective in the detection of low-abundant taxon. Our results point out a significantly higher relative abundance of Anaerolineaceae bacterium oral taxon 439 in patients with moderate to severe periodontitis vs patients without history of periodontitis, which was maintained when the comparison was restricted to type 2 diabetics.


Assuntos
Placa Dentária , Diabetes Mellitus Tipo 2 , Metagenômica , Microbiota , Boca , Periodontite , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/microbiologia , Gengiva , Humanos , Boca/microbiologia , Periodontite/complicações , Periodontite/microbiologia
15.
Mol Immunol ; 112: 322-329, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31238287

RESUMO

OBJECTIVE: The morbidity and prevalence of type 2 diabetes mellitus (DM) are increasing in the elderly population. Interleukin 37 (IL-37) play important roles in anti-inflammatory and anti-bacteria immune responses, but its role in the development of type 2 DM in the elderly is unclear. Therefore, we investigated whether IL-37 is associated with type 2 DM in the elderly and the underlying mechanism. METHODS: Hospitalized patients (aged 65-95 years) with recently diagnosed type 2 diabetes mellitus were studied retrospectively and compared with healthy subjects without glucose metabolism abnormalities. A diabetic mouse model was established by feeding ob/ob mice (C57BL/6) a high-fat, carbohydrate-free diet. Plasma glucose and insulin levels were determined by glucose oxidase assay and radioimmunoassay, respectively. The IL-37 expression level was determined by real-time PCR, western blot and ELISA (Enzyme-linked immunoassay). RESULTS: Statistic analysis showed that the IL-37 level was significantly associated with type 2 DM and insulin resistance in the elderly. The patients were then divided into insulin therapy sensitive and resistant group according to their response to insulin therapy. Data showed that the IL-37 was highly expressed in the insulin therapy sensitive group. And this was related to the less severe gut microbiota dysbiosis. In the mice model, overexpressing the IL-37 could suppress the gut microbiota dysbiosis and also the diabetes development. CONCLUSION: Thus our results showed that higher IL-37 was associated with increased insulin sensitive in elderly type 2 DM patients through suppressing the gut microbiota dysbiosis.


Assuntos
Diabetes Mellitus Tipo 2/imunologia , Disbiose/imunologia , Microbioma Gastrointestinal/imunologia , Interleucina-1/imunologia , Idoso , Idoso de 80 Anos ou mais , Animais , Linhagem Celular , Diabetes Mellitus Experimental/imunologia , Diabetes Mellitus Experimental/microbiologia , Diabetes Mellitus Tipo 2/microbiologia , Dieta Hiperlipídica/efeitos adversos , Disbiose/microbiologia , Feminino , Células HEK293 , Humanos , Resistência à Insulina/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL
16.
Nature ; 569(7758): 663-671, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31142858

RESUMO

Type 2 diabetes mellitus (T2D) is a growing health problem, but little is known about its early disease stages, its effects on biological processes or the transition to clinical T2D. To understand the earliest stages of T2D better, we obtained samples from 106 healthy individuals and individuals with prediabetes over approximately four years and performed deep profiling of transcriptomes, metabolomes, cytokines, and proteomes, as well as changes in the microbiome. This rich longitudinal data set revealed many insights: first, healthy profiles are distinct among individuals while displaying diverse patterns of intra- and/or inter-personal variability. Second, extensive host and microbial changes occur during respiratory viral infections and immunization, and immunization triggers potentially protective responses that are distinct from responses to respiratory viral infections. Moreover, during respiratory viral infections, insulin-resistant participants respond differently than insulin-sensitive participants. Third, global co-association analyses among the thousands of profiled molecules reveal specific host-microbe interactions that differ between insulin-resistant and insulin-sensitive individuals. Last, we identified early personal molecular signatures in one individual that preceded the onset of T2D, including the inflammation markers interleukin-1 receptor agonist (IL-1RA) and high-sensitivity C-reactive protein (CRP) paired with xenobiotic-induced immune signalling. Our study reveals insights into pathways and responses that differ between glucose-dysregulated and healthy individuals during health and disease and provides an open-access data resource to enable further research into healthy, prediabetic and T2D states.


Assuntos
Biomarcadores/metabolismo , Biologia Computacional , Diabetes Mellitus Tipo 2/microbiologia , Microbioma Gastrointestinal , Interações entre Hospedeiro e Microrganismos/genética , Estado Pré-Diabético/microbiologia , Proteoma/metabolismo , Transcriptoma , Adulto , Idoso , Antibacterianos/administração & dosagem , Biomarcadores/análise , Estudos de Coortes , Conjuntos de Dados como Assunto , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Feminino , Glucose/metabolismo , Voluntários Saudáveis , Humanos , Inflamação/metabolismo , Vacinas contra Influenza/imunologia , Insulina/metabolismo , Resistência à Insulina , Estudos Longitudinais , Masculino , Microbiota/fisiologia , Pessoa de Meia-Idade , Estado Pré-Diabético/genética , Estado Pré-Diabético/metabolismo , Infecções Respiratórias/genética , Infecções Respiratórias/metabolismo , Infecções Respiratórias/microbiologia , Infecções Respiratórias/virologia , Estresse Fisiológico , Vacinação/estatística & dados numéricos
17.
Acta Odontol Scand ; 77(7): 508-516, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31145647

RESUMO

Aims: Oral candidiasis is a major oral manifestation of uncontrolled diabetes mellitus, and a number of cofactors are associated with the pathogenesis of this infection. Here, we describe the prevalence of oral Candida in a Sri Lankan cohort of type 2 diabetes mellitus and risk factors that predispose them to this common fungal infection. Methods: A case-control study was conducted in 250 diabetics with type 2 diabetes and 81 nondiabetic controls. Clinical and demographic data were collected using an interviewer administered questionnaire, and patient records. Oral rinse samples were collected to determine the candidal carriage, and the resultant yeast growth was quantified and speciated using multiplex-PCR and phenotypic analyses. Chi-square test (χ2 test) and Fisher exact test were used for the determination of the significant relationships between risk factors and oral candidiasis. Results: The oral prevalence of Candida species among both groups was similar (81%) although a significantly higher proportion of diabetics (32.8%) yielded >2000 CFU/mL of yeasts compared with only 12.3% of the healthy controls (p < .05). Significant associations were noted between oral candidal carriage amongst diabetics, and (i) denture wearing, (ii) female gender and (iii) cigarette smoking (all, p < .05). Amongst both groups, C.albicans was the most common Candida species isolated followed by C. parapsilosis, C. tropicalis and C. glabrata. Conclusions: The oral infestation of Candida in our Sri Lankan cohort of diabetics is significantly higher than their healthy counterparts, and co-carriage of multiple yeast species is a common finding in the study population. As there are no previous such reports of the latter phenomenon particularly from the Asian region it is noteworthy, mainly in view of the recent data on the emergence of drug-resistant yeast species the world over.


Assuntos
Candida/isolamento & purificação , Candidíase Bucal/diagnóstico , Complicações do Diabetes , Diabetes Mellitus Tipo 2/diagnóstico , Adulto , Candida/classificação , Candida albicans/isolamento & purificação , Candidíase Bucal/epidemiologia , Candidíase Bucal/microbiologia , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/microbiologia , Feminino , Humanos , Masculino , Prevalência , Fatores de Risco , Distribuição por Sexo , Sri Lanka/epidemiologia
18.
Food Funct ; 10(5): 2935-2946, 2019 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-31070649

RESUMO

In the present study, we aimed to investigate the therapeutic mechanisms of carrot juice fermented with Lactobacillus rhamnosus GG (LGG) on type 2 diabetic mellitus (T2DM) based on the regulation of gut microbiota. Carrot juice fermented with LGG was enriched with free phenols, organic acids and short-chain fatty acids (SCFAs). Supplementation of carrot juice fermented with LGG (DFCL) could favorably regulate blood glucose, insulin, antioxidant capacity and morphology of the pancreas and kidney in the diabetic rats, accompanied by an increase of SCFAs in the cecum. Furthermore, high-throughput sequencing (HTS) analysis revealed that DFCL supplementation altered the composition of gut microbiota, showing increased relative abundances of functionally relevant enterotypes, such as Christensenellaceae_R-7_group, Oscillibacter, Ruminococcaceae_UCG-013, Lachnospiraceae_NK4A136_group and Akkermansia. In addition, Spearman's correlation analysis revealed that Desulfovibrio, Ruminococcaceae and Alloprevotella were closely correlated with biochemical biomarkers. Meanwhile, DFCL treatment regulated the expressions of genes involved in glucose metabolism at the mRNA and protein levels.


Assuntos
Daucus carota/metabolismo , Diabetes Mellitus Tipo 2/dietoterapia , Diabetes Mellitus Tipo 2/microbiologia , Sucos de Frutas e Vegetais/análise , Microbioma Gastrointestinal , Animais , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Bactérias/metabolismo , Glicemia/metabolismo , Ceco/microbiologia , Daucus carota/química , Daucus carota/microbiologia , Diabetes Mellitus Tipo 2/metabolismo , Ácidos Graxos Voláteis/metabolismo , Sucos de Frutas e Vegetais/microbiologia , Humanos , Insulina/metabolismo , Lactobacillus rhamnosus/metabolismo , Masculino , Ratos , Ratos Wistar
19.
Can J Diabetes ; 43(3): 224-231, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30929665

RESUMO

The gut microbiota is an important regulator of host metabolism. Metagenome analyses have demonstrated that the gut microbiota differs between patients with type 2 diabetes and healthy subjects, and several studies have shown that impaired glucose metabolism is associated with decreased levels of butyrate-producing bacteria. Gut microbiota-produced metabolites, such as short-chain fatty acids, amino acid derivatives and secondary bile acids, participate in metabolic and immunologic processes and, hence, pose putative links between the gut microbiota and glucose homeostasis. Strategies to prevent and treat type 2 diabetes through manipulation of the gut microbiota are being developed. These include replacement of the gut microbiota by fecal transplantation, consumption of fibres to promote the function and growth of beneficial bacteria and treatment with probiotic bacterial strains. Furthermore, it has been shown that many drugs, including drugs used for treatment of diabetes, have major impacts on gut microbiota and, thereby, potentially on glucose metabolism. In particular, the commonly used drug metformin has been shown to influence the functional capacity of the gut microbiota, and recent evidence indicates that this may contribute to the antidiabetes effect of metformin.


Assuntos
Diabetes Mellitus Tipo 2/microbiologia , Disbiose/terapia , Microbioma Gastrointestinal , Glucose/metabolismo , Diabetes Mellitus Tipo 2/imunologia , Diabetes Mellitus Tipo 2/metabolismo , Dietoterapia , Fibras na Dieta/uso terapêutico , Transplante de Microbiota Fecal , Microbioma Gastrointestinal/efeitos dos fármacos , Humanos , Imunidade Inata , Metformina/efeitos adversos , Metformina/uso terapêutico , Probióticos/uso terapêutico
20.
Food Funct ; 10(4): 1915-1927, 2019 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-30869673

RESUMO

Type 2 diabetes mellitus (T2DM) is closely correlated with chronic low-grade inflammation and gut dysbiosis. Prebiotic inulin (INU) is conducive to modulate gut dysbiosis. However, the impact of dietary inulin on the diverse stages of T2DM remains largely unknown. In the present study, according to the fasting blood glucose (FBG) and oral glucose tolerance tests (OGTT), mice were randomly divided into six groups (15 mice per group): pre-diabetic group (PDM group); inulin-treated pre-diabetic group (INU/PDM group); early diabetic group (EDM group); inulin-treated early diabetic group (INU/EDM group); diabetic group (DM group); inulin-treated diabetic group (INU/DM group). All animal experiments were approved by the Ethics Committee of the General Hospital of Ningxia Medical University (No. 2016-232). After 6 weeks of inulin intervention, the mice were euthanized and the associated indicators were investigated. Dietary inulin significantly reduced FBG, body weights (BWs), glycated hemoglobin (GHb), blood lipid, plasma lipopolysaccharide (LPS), interleukin (IL)-6, tumor necrosis factor (TNF)-α and IL-17A in the three inulin-treated groups compared to the untreated groups. But for IL-17A, there remained no significant difference between the PDM group and the INU/PDM group. Moreover, the anti-inflammatory IL-10 showed significant alteration in the INU/PDM and INU/EDM groups, but no significant alteration in the INU/DM group. Sequencing analysis of the gut microbiota showed an elevation in the relative abundance of Cyanobacteria and Bacteroides and a reduction in the relative abundance of Ruminiclostridium_6 in three inulin-treated different stages of T2DM groups, as well as a reduction in the relative abundance of Deferribacteres and Tenericutes in the INU/DM group. A reduction in the relative abundance of Mucispirillum was detected in the INU/PDM and INU/EDM groups. Correlation analysis revealed that Cyanobacteria and Bacteroides abundance were positively correlated with IL-10; Deferribacteres, Tenericutes, Mucispirillum and Ruminiclostridium_6 abundance were closely related to IL-6, TNF-α or IL-17A respectively. Additionally, Mucispirillum and Ruminiclostridium_6 abundance were positively correlated with LPS. Taken together, dietary inulin alleviated the diverse stages of T2DM via suppressing inflammation and modulating gut microbiota.


Assuntos
Diabetes Mellitus Tipo 2/imunologia , Diabetes Mellitus Tipo 2/microbiologia , Microbioma Gastrointestinal/efeitos dos fármacos , Inulina/administração & dosagem , Prebióticos/administração & dosagem , Animais , Bactérias/classificação , Bactérias/efeitos dos fármacos , Bactérias/genética , Bactérias/isolamento & purificação , Diabetes Mellitus Tipo 2/metabolismo , Feminino , Teste de Tolerância a Glucose , Hemoglobina A Glicada/metabolismo , Humanos , Interleucina-17/imunologia , Interleucina-6/imunologia , Camundongos , Camundongos Obesos , Fator de Necrose Tumoral alfa/imunologia
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