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1.
Nutrients ; 13(1)2021 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-33440675

RESUMO

The risk of recurrence of estrogen receptor-positive breast cancer remains constant, even 20 years after diagnosis. Recurrence may be more likely in patients pre-programmed for it already in the womb, such as in the daughters born to obese mothers. Maternal obesity persistently alters offspring's gut microbiota and impairs tumor immune responses. To investigate if the gut dysbiosis is linked to increased risk of mammary cancer recurrence in the offspring of obese rat dams, we fed adult offspring genistein which is known to have beneficial effects on the gut bacteria. However, the effects of genistein on breast cancer remain controversial. We found that genistein intake after tamoxifen response prevented the increased risk of local recurrence in the offspring of obese dams but had no effect on the control offspring. A significant increase in the abundance of inflammatory Prevotellaceae and Enterobacteriaceae, and a reduction in short-chain fatty acid producing Clostridiaceae was observed in the offspring of obese dams. Genistein supplementation reversed these changes as well as reversed increased gut metabolite N-acetylvaline levels which are linked to increased all-cause mortality. Genistein supplementation also reduced genotoxic tyramine levels, increased metabolites improving pro-resolving phase of inflammation, and reversed the elevated tumor mRNA expression of multiple immunosuppressive genes in the offspring of obese dams. If translatable to breast cancer patients, attempts to prevent breast cancer recurrences might need to focus on dietary modifications which beneficially modify the gut microbiota.


Assuntos
Microbioma Gastrointestinal/efeitos dos fármacos , Genisteína/farmacologia , Neoplasias Mamárias Animais/microbiologia , Obesidade/microbiologia , Efeitos Tardios da Exposição Pré-Natal/microbiologia , Animais , Feminino , Neoplasias Mamárias Animais/tratamento farmacológico , Obesidade/etiologia , Gravidez , Efeitos Tardios da Exposição Pré-Natal/etiologia , Ratos , Ratos Sprague-Dawley
2.
Front Cell Infect Microbiol ; 10: 575559, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33363049

RESUMO

The current COVID-19 pandemic is a great challenge for worldwide researchers in the human microbiota area because the mechanisms and long-term effects of the infection at the GI level are not yet deeply understood. In the current review, scientific literature including original research articles, clinical studies, epidemiological reports, and review-type articles concerning human intestinal infection with SARS-CoV-2 and the possible consequences on the microbiota were reviewed. Moreover, the following aspects pertaining to COVID-19 have also been discussed: transmission, resistance in the human body, the impact of nutritional status in relation to the intestinal microbiota, and the impact of comorbid metabolic disorders such as inflammatory bowel disease (IBS), obesity, and type two diabetes (T2D). The articles investigated show that health, age, and nutritional status are associated with specific communities of bacterial species in the gut, which could influence the clinical course of COVID-19 infection. Fecal microbiota alterations were associated with fecal concentrations of SARS-CoV-2 and COVID-19 severity. Patients suffering from metabolic and gastrointestinal (GI) disorders are thought to be at a moderate-to-high risk of infection with SARS-CoV-2, indicating the direct implication of gut dysbiosis in COVID-19 severity. However, additional efforts are required to identify the initial GI symptoms of COVID-19 for possible early intervention.


Assuntos
/microbiologia , Disbiose/etiologia , Microbioma Gastrointestinal , Pandemias , /fisiologia , Animais , /epidemiologia , Comorbidade , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/microbiologia , Reservatórios de Doenças/virologia , Enterócitos/patologia , Enterócitos/virologia , Fezes/microbiologia , Fezes/virologia , Gastroenteropatias/etiologia , Gastroenteropatias/microbiologia , Humanos , Síndrome do Intestino Irritável/epidemiologia , Síndrome do Intestino Irritável/microbiologia , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/microbiologia , Obesidade/epidemiologia , Obesidade/microbiologia , Fatores de Risco , /patogenicidade
3.
J Transl Med ; 18(1): 415, 2020 11 07.
Artigo em Inglês | MEDLINE | ID: mdl-33160363

RESUMO

On December 12, 2019 a new coronavirus (SARS-CoV-2) emerged in Wuhan, China, triggering a pandemic of severe acute respiratory syndrome in humans (COVID-19). Today, the scientific community is investing all the resources available to find any therapy and prevention strategies to defeat COVID-19. In this context, immunonutrition can play a pivotal role in improving immune responses against viral infections. Immunonutrition has been based on the concept that malnutrition impairs immune function. Therefore, immunonutrition involves feeding enriched with various pharmaconutrients (Omega 3 Fatty Acids, Vitamin C, Arginine, Glutamine, Selenium, Zinc, Vitamin, E and Vitamin D) to modulate inflammatory responses, acquired immune response and to improve patient outcomes. In literature, significant evidences indicate that obesity, a malnutrition state, negatively impacts on immune system functionality and on host defense, impairing protection from infections. Immunonutrients can promote patient recovery by inhibiting inflammatory responses and regulating immune function. Immune system dysfunction is considered to increase the risk of viral infections, such as SARS-CoV-2, and was observed in different pathological situations. Obese patients develop severe COVID-19 sequelae, due to the high concentrations of TNF-α, MCP-1 and IL-6 produced in the meantime by visceral and subcutaneous adipose tissue and by innate immunity. Moreover, leptin, released by adipose tissue, helps to increase inflammatory milieu with a dysregulation of the immune response. Additionally, gut microbiota plays a crucial role in the maturation, development and functions of both innate and adaptive immune system, as well as contributing to develop obese phenotype. The gut microbiota has been shown to affect lung health through a vital crosstalk between gut microbiota and lungs, called the "gut-lung axis". This axis communicates through a bi-directional pathway in which endotoxins, or microbial metabolites, may affect the lung through the blood and when inflammation occurs in the lung, this in turn can affect the gut microbiota. Therefore, the modulation of gut microbiota in obese COVID-19 patients can play a key role in immunonutrition therapeutic strategy. This umbrella review seeks to answer the question of whether a nutritional approach can be used to enhance the immune system's response to obesity in obese patients affected by COVID-19.


Assuntos
Betacoronavirus/fisiologia , Infecções por Coronavirus/complicações , Infecções por Coronavirus/imunologia , Sistema Imunitário/patologia , Sistema Imunitário/virologia , Fenômenos Fisiológicos da Nutrição , Obesidade/complicações , Obesidade/virologia , Pneumonia Viral/complicações , Pneumonia Viral/imunologia , Infecções por Coronavirus/microbiologia , Humanos , Microbiota , Obesidade/microbiologia , Pandemias , Pneumonia Viral/microbiologia
5.
Nat Commun ; 11(1): 4982, 2020 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-33020474

RESUMO

Nonalcoholic fatty liver disease (NAFLD) is associated with obesity but also found in non-obese individuals. Gut microbiome profiles of 171 Asians with biopsy-proven NAFLD and 31 non-NAFLD controls are analyzed using 16S rRNA sequencing; an independent Western cohort is used for external validation. Subjects are classified into three subgroups according to histological spectra of NAFLD or fibrosis severity. Significant alterations in microbiome diversity are observed according to fibrosis severity in non-obese, but not obese, subjects. Ruminococcaceae and Veillonellaceae are the main microbiota associated with fibrosis severity in non-obese subjects. Furthermore, stool bile acids and propionate are elevated, especially in non-obese subjects with significant fibrosis. Fibrosis-related Ruminococcaceae and Veillonellaceae species undergo metagenome sequencing, and four representative species are administered in three mouse NAFLD models to evaluate their effects on liver damage. This study provides the evidence for the role of the microbiome in the liver fibrosis pathogenesis, especially in non-obese subjects.


Assuntos
Bactérias/isolamento & purificação , Microbioma Gastrointestinal/fisiologia , Hepatopatia Gordurosa não Alcoólica/microbiologia , Hepatopatia Gordurosa não Alcoólica/patologia , Animais , Bactérias/classificação , Bactérias/genética , Bactérias/metabolismo , Ácidos e Sais Biliares/análise , Ácidos e Sais Biliares/metabolismo , Biomarcadores , Fezes/química , Fezes/microbiologia , Fibrose , Microbioma Gastrointestinal/genética , Humanos , Cirrose Hepática/diagnóstico , Cirrose Hepática/metabolismo , Cirrose Hepática/microbiologia , Cirrose Hepática/patologia , Camundongos , Hepatopatia Gordurosa não Alcoólica/metabolismo , Obesidade/metabolismo , Obesidade/microbiologia , Obesidade/patologia , Propionatos/análise , Propionatos/metabolismo , RNA Ribossômico 16S/genética , Reprodutibilidade dos Testes
6.
Elife ; 92020 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-32930095

RESUMO

Obesity and diabetes are established comorbidities for COVID-19. Adipose tissue demonstrates high expression of ACE2 which SARS- CoV-2 exploits to enter host cells. This makes adipose tissue a reservoir for SARS-CoV-2 viruses and thus increases the integral viral load. Acute viral infection results in ACE2 downregulation. This relative deficiency can lead to disturbances in other systems controlled by ACE2, including the renin-angiotensin system. This will be further increased in the case of pre-conditions with already compromised functioning of these systems, such as in patients with obesity and diabetes. Here, we propose that interactions of virally-induced ACE2 deficiency with obesity and/or diabetes leads to a synergistic further impairment of endothelial and gut barrier function. The appearance of bacteria and/or their products in the lungs of obese and diabetic patients promotes interactions between viral and bacterial pathogens, resulting in a more severe lung injury in COVID-19.


Assuntos
Infecções por Coronavirus/microbiologia , Diabetes Mellitus/microbiologia , Obesidade/microbiologia , Pneumonia Viral/microbiologia , Tecido Adiposo/metabolismo , Tecido Adiposo/virologia , Animais , Betacoronavirus/isolamento & purificação , Comorbidade , Infecções por Coronavirus/complicações , Infecções por Coronavirus/metabolismo , Infecções por Coronavirus/virologia , Complicações do Diabetes/metabolismo , Complicações do Diabetes/microbiologia , Complicações do Diabetes/virologia , Diabetes Mellitus/metabolismo , Diabetes Mellitus/virologia , Regulação para Baixo , Interações entre Hospedeiro e Microrganismos , Humanos , Interações Microbianas , Obesidade/metabolismo , Obesidade/virologia , Pandemias , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/complicações , Pneumonia Viral/metabolismo , Pneumonia Viral/virologia , Sistema Renina-Angiotensina , Carga Viral
7.
Ecotoxicol Environ Saf ; 203: 111041, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32888612

RESUMO

Although the production and use of PCB153 have been banned globally, PCB153 pollution remains because of its persistence and long half-life in the environment. There is ongoing evidence that exposure to PCB153 may influence gut microbiota health and increase the risk of host health. It is needed to illuminate whether there are associations between gut microbiota dysregulation and PCB153-induced host diseases. Importantly, it is urgently needed to find specific strains as biomarkers to monitor PCB153 pollution and associated disorders. The work aims to investigate the change of gut microbiota composition, structure and diversity and various host physiological indexes, to ravel the chain causality of PCB153, gut microbiota health and host health, and to find potential gut microbiota markers for PCB153 pollution. Here, adult female mice were administrated with PCB153. Obtained results indicated that PCB153 led to gut microbiota health deterioration. PCB153 exposure also induced obesity, hepatic lipid accumulation, abdominal adipose tissue depots and dyslipidemia in mice. Furthermore, specific gut microbiota significantly correlated with the host health indexes. This work provides support for the relationship between gut microbiota aberrance derived from PCB153 and risk of host health, and offers some indications of possible indicative functions of gut microbiota on PCB153 pollution.


Assuntos
Dislipidemias/induzido quimicamente , Monitoramento Ambiental/métodos , Poluentes Ambientais/toxicidade , Microbioma Gastrointestinal/efeitos dos fármacos , Obesidade/induzido quimicamente , Bifenilos Policlorados/toxicidade , Animais , Biomarcadores/análise , Colo/microbiologia , Dislipidemias/metabolismo , Dislipidemias/microbiologia , Feminino , Conteúdo Gastrointestinal/microbiologia , Microbioma Gastrointestinal/genética , Expressão Gênica/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/metabolismo , Obesidade/microbiologia , RNA Ribossômico 16S
8.
Nat Commun ; 11(1): 4018, 2020 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-32782301

RESUMO

The gut microbiome is an ecosystem that involves complex interactions. Currently, our knowledge about the role of the gut microbiome in health and disease relies mainly on differential microbial abundance, and little is known about the role of microbial interactions in the context of human disease. Here, we construct and compare microbial co-abundance networks using 2,379 metagenomes from four human cohorts: an inflammatory bowel disease (IBD) cohort, an obese cohort and two population-based cohorts. We find that the strengths of 38.6% of species co-abundances and 64.3% of pathway co-abundances vary significantly between cohorts, with 113 species and 1,050 pathway co-abundances showing IBD-specific effects and 281 pathway co-abundances showing obesity-specific effects. We can also replicate these IBD microbial co-abundances in longitudinal data from the IBD cohort of the integrative human microbiome (iHMP-IBD) project. Our study identifies several key species and pathways in IBD and obesity and provides evidence that altered microbial abundances in disease can influence their co-abundance relationship, which expands our current knowledge regarding microbial dysbiosis in disease.


Assuntos
Microbioma Gastrointestinal , Doenças Inflamatórias Intestinais/microbiologia , Consórcios Microbianos , Obesidade/microbiologia , Adulto , Bactérias/crescimento & desenvolvimento , Bactérias/isolamento & purificação , Bactérias/metabolismo , Estudos de Coortes , Disbiose/metabolismo , Disbiose/microbiologia , Feminino , Microbioma Gastrointestinal/genética , Especificidade de Hospedeiro , Humanos , Doenças Inflamatórias Intestinais/metabolismo , Masculino , Redes e Vias Metabólicas , Pessoa de Meia-Idade , Obesidade/metabolismo
9.
Nutr Metab Cardiovasc Dis ; 30(9): 1500-1511, 2020 08 28.
Artigo em Inglês | MEDLINE | ID: mdl-32620337

RESUMO

BACKGROUND AND AIMS: Consumption of soy foods has been associated with protection against cardiometabolic disease, but the mechanisms are incompletely understood. We hypothesized that habitual soy food consumption associates with gut microbiome composition, metabolite production, and the interaction between diet, microbiota and metabolites. METHODS AND RESULTS: We analyzed dietary soy intake, plasma and stool metabolites, and gut microbiome data from two independent cross-sectional samples of healthy US individuals (N = 75 lean or overweight, and N = 29 obese). Habitual soy intake associated with several circulating metabolites. There was a significant interaction between soy intake and gut microbiome composition, as defined by gut enterotype, on metabolites in plasma and stool. Soy consumption associated with reduced systolic blood pressure, but only in a subset of individuals defined by their gut microbiome enterotype, suggesting that responsiveness to soy may be dependent on microbiome composition. Soy intake was associated with differences in specific microbial taxa, including two taxa mapping to genus Dialister and Prevotella which appeared to be suppressed by high soy intake We identified context-dependent effects of these taxa, where presence of Prevotella was associated with higher blood pressure and a worse cardiometabolic profile, but only in the absence of Dialister. CONCLUSIONS: The gut microbiome is an important intermediate in the interplay between dietary soy intake and systemic metabolism. Consumption of soy foods may shape the microbiome by suppressing specific taxa, and may protect against hypertension only in individuals with soy-responsive microbiota. CLINICAL TRIALS REGISTRY: NCT02010359 at clinicaltrials.gov.


Assuntos
Pressão Sanguínea , Metabolismo Energético , Microbioma Gastrointestinal , Intestinos/microbiologia , Obesidade/dietoterapia , Alimentos de Soja , Adolescente , Adulto , Biomarcadores/sangue , Estudos Transversais , Fezes/química , Fezes/microbiologia , Feminino , Interações Hospedeiro-Patógeno , Humanos , Masculino , Metabolômica , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/microbiologia , Obesidade/fisiopatologia , Pennsylvania , Ribotipagem , Fatores de Tempo , Resultado do Tratamento , Estados Unidos , Adulto Jovem
10.
Am J Physiol Endocrinol Metab ; 319(1): E203-E216, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32516027

RESUMO

Studies suggest the gut microbiota contributes to the development of obesity and metabolic syndrome. Exercise alters microbiota composition and diversity and is protective of these maladies. We tested whether the protective metabolic effects of exercise are mediated through fecal components through assessment of body composition and metabolism in recipients of fecal microbiota transplantation (FMT) from exercise-trained (ET) mice fed normal or high-energy diets. Donor C57BL/6J mice were fed a chow or high-fat, high-sucrose diet (HFHS) for 4 wk to induce obesity and glucose intolerance. Mice were divided into sedentary (Sed) or ET groups (6 wk treadmill-based ET) while maintaining their diets, resulting in four donor groups: chow sedentary (NC-Sed) or ET (NC-ET) and HFHS sedentary (HFHS-Sed) or ET (HFHS-ET). Chow-fed recipient mice were gavaged with feces from the respective donor groups weekly, creating four groups (NC-Sed-R, NC-ET-R, HFHS-Sed-R, HFHS-ET-R), and body composition and metabolism were assessed. The HFHS diet led to glucose intolerance and obesity in the donors, whereas exercise training (ET) restrained adiposity and improved glucose tolerance. No donor group FMT altered recipient body composition. Despite unaltered adiposity, glucose levels were disrupted when challenged in mice receiving feces from HFHS-fed donors, irrespective of donor-ET status, with a decrease in insulin-stimulated glucose clearance into white adipose tissue and large intestine and specific changes in the recipient's microbiota composition observed. FMT can transmit HFHS-induced disrupted glucose metabolism to recipient mice independently of any change in adiposity. However, the protective metabolic effect of ET on glucose metabolism is not mediated through fecal factors.


Assuntos
Dieta Hiperlipídica , Sacarose na Dieta , Transplante de Microbiota Fecal , Intolerância à Glucose/microbiologia , Obesidade/microbiologia , Condicionamento Físico Animal , Comportamento Sedentário , Adiposidade , Animais , Microbioma Gastrointestinal , Glucose/metabolismo , Intolerância à Glucose/metabolismo , Masculino , Camundongos , Obesidade/metabolismo , Distribuição Aleatória
11.
BMC Bioinformatics ; 21(1): 225, 2020 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-32493208

RESUMO

BACKGROUND: Advances in DNA sequencing have offered researchers an unprecedented opportunity to better study the variety of species living in and on the human body. However, the analysis of microbiome data is complicated by several challenges. First, the sequencing depth may vary by orders of magnitude across samples. Second, species are rare and the data often contain many zeros. Third, the specimen is a fraction of the microbial ecosystem, and so the data are compositional carrying only relative information. Other characteristics of microbiome data include pronounced over-dispersion in taxon abundances, and the existence of a phylogenetic tree that relates all bacterial species. To address some of these challenges, microbiome analysis workflows often normalize the read counts prior to downstream analysis. However, there are limitations in the current literature on the normalization of microbiome data. RESULTS: Under the multinomial distribution for the read counts and a prior for the unknown proportions, we propose an empirical Bayes approach to microbiome data normalization. Using a tree-based extension of the Dirichlet prior, we further extend our method by incorporating the phylogenetic tree into the normalization process. We study the impact of normalization on differential abundance analysis. In the presence of tree structure, we propose a phylogeny-aware detection procedure. CONCLUSIONS: Extensive simulations and gut microbiome data applications are conducted to demonstrate the superior performance of our empirical Bayes method over other normalization methods, and over commonly-used methods for differential abundance testing. Original R scripts are available at GitHub (https://github.com/liudoubletian/eBay).


Assuntos
Microbiota , Algoritmos , Bactérias/genética , Sequência de Bases , Teorema de Bayes , Índice de Massa Corporal , Criança , Simulação por Computador , Microbioma Gastrointestinal/genética , Humanos , Obesidade/microbiologia , Filogenia
12.
Sci Rep ; 10(1): 7850, 2020 05 12.
Artigo em Inglês | MEDLINE | ID: mdl-32398726

RESUMO

Environmental and genetic factors are associated with pandemic obesity since childhood. However, the association of overweight-obesity with these factors, acting as a consortium, has been scarcely studied in children. We aimed here to assess the probabilities of being overweighed-obese in a randomly recruited cohort of Spanish children and adolescents (n = 415, 5-17 years-old) by estimating the odds ratios for different predictor variables, and their relative importance in the prediction. The predictor variables were ethnicity, age, sex, adherence to the Mediterranean diet (KIDMED), physical activity, urolithin metabotypes (UM-A, UM-B and UM-0) as biomarkers of the gut microbiota, and 53 single-nucleotide polymorphisms (SNPs) from 43 genes mainly related to obesity and cardiometabolic diseases. A proportional-odds logistic ordinal regression, validated through bootstrap, was used to model the data. While every variable was not independently associated with overweight-obesity, however, the ordinal logistic model revealed that overweight-obesity prevalence was related to being a young boy with either UM-B or UM-0, low KIDMED score and high contribution of a consortium of 24 SNPs, being rs1801253-ADRB1, rs4343-ACE, rs8061518-FTO, rs1130864-CRP, rs659366-UCP2, rs6131-SELP, rs12535708-LEP, rs1501299-ADIPOQ, rs708272-CETP and rs2241766-ADIPOQ the top-ten contributing SNPs. Additional research should confirm and complete this model by including dietary interventions and the individuals' gut microbiota composition.


Assuntos
Cumarínicos/metabolismo , Dieta Mediterrânea , Microbioma Gastrointestinal , Obesidade/genética , Obesidade/microbiologia , Polimorfismo de Nucleotídeo Único , Adolescente , Criança , Estudos de Coortes , Exercício Físico , Feminino , Humanos , Masculino , Obesidade/metabolismo , Razão de Chances
13.
J Appl Oral Sci ; 28: e20190694, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32428060

RESUMO

Objective Obesity is a chronic disease that negatively affects an individual's general and oral health. The present study aimed to compare the clinical and microbiological effects of non-surgical periodontal therapy with the full mouth disinfection (FMD) protocol on obese and non-obese individuals at 9 months post-therapy. Methodology This clinical study was first submitted and approved by the Ethics Committee. Fifty-five obese patients and 39 non-obese patients with periodontitis were evaluated. The full-mouth periodontal clinical parameters, clinical attachment level (CAL), probing depth (PD), gingival index (GI), and plaque index (PI), were monitored at baseline, 3, 6, and 9 months after periodontal treatment with full mouth disinfection (FMD) protocol. The mean count of Tannerella forsythia , Porphyromonas gingivalis , Treponema Denticola , and Aggregatibacter actinomycetemcomitans was determined by quantitative polymerase chain reaction on subgingival biofilm samples. Demographic data were assessed by Chi-square test. For clinical and microbiological parameters, two-factor repeated-measures ANOVA was used. Results In both groups, periodontal therapy using the one-stage full-mouth disinfection protocol significantly improved CAL, PD, GI, and PI (p<0.05). Obese and non-obese patients equally responded to non-surgical periodontal therapy (p>0.05). Microbial count found no major differences (p>0.05) between obese and non-obese individuals who had undergone non-surgical periodontal therapy. Conclusions Obesity did not affect the clinical and microbiological outcomes of non-surgical periodontal therapy.


Assuntos
Obesidade/microbiologia , Periodontite/microbiologia , Periodontite/terapia , Adulto , Aggregatibacter actinomycetemcomitans/isolamento & purificação , Análise de Variância , Antropometria , Índice de Placa Dentária , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Obesidade/fisiopatologia , Índice Periodontal , Porphyromonas gingivalis/isolamento & purificação , Estudos Prospectivos , Fatores de Risco , Estatísticas não Paramétricas , Tannerella forsythia/isolamento & purificação , Fatores de Tempo , Resultado do Tratamento , Treponema denticola/isolamento & purificação
14.
Nature ; 581(7808): 310-315, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32433607

RESUMO

Microbiome community typing analyses have recently identified the Bacteroides2 (Bact2) enterotype, an intestinal microbiota configuration that is associated with systemic inflammation and has a high prevalence in loose stools in humans1,2. Bact2 is characterized by a high proportion of Bacteroides, a low proportion of Faecalibacterium and low microbial cell densities1,2, and its prevalence varies from 13% in a general population cohort to as high as 78% in patients with inflammatory bowel disease2. Reported changes in stool consistency3 and inflammation status4 during the progression towards obesity and metabolic comorbidities led us to propose that these developments might similarly correlate with an increased prevalence of the potentially dysbiotic Bact2 enterotype. Here, by exploring obesity-associated microbiota alterations in the quantitative faecal metagenomes of the cross-sectional MetaCardis Body Mass Index Spectrum cohort (n = 888), we identify statin therapy as a key covariate of microbiome diversification. By focusing on a subcohort of participants that are not medicated with statins, we find that the prevalence of Bact2 correlates with body mass index, increasing from 3.90% in lean or overweight participants to 17.73% in obese participants. Systemic inflammation levels in Bact2-enterotyped individuals are higher than predicted on the basis of their obesity status, indicative of Bact2 as a dysbiotic microbiome constellation. We also observe that obesity-associated microbiota dysbiosis is negatively associated with statin treatment, resulting in a lower Bact2 prevalence of 5.88% in statin-medicated obese participants. This finding is validated in both the accompanying MetaCardis cardiovascular disease dataset (n = 282) and the independent Flemish Gut Flora Project population cohort (n = 2,345). The potential benefits of statins in this context will require further evaluation in a prospective clinical trial to ascertain whether the effect is reproducible in a randomized population and before considering their application as microbiota-modulating therapeutics.


Assuntos
Disbiose/epidemiologia , Disbiose/prevenção & controle , Microbioma Gastrointestinal/efeitos dos fármacos , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Bacteroides/isolamento & purificação , Estudos de Coortes , Estudos Transversais , Faecalibacterium/isolamento & purificação , Fezes/microbiologia , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Doenças Inflamatórias Intestinais/microbiologia , Masculino , Obesidade/microbiologia , Prevalência
15.
Sci Rep ; 10(1): 6118, 2020 04 09.
Artigo em Inglês | MEDLINE | ID: mdl-32273571

RESUMO

Obesity has emerged as a major global health problem and is associated with various diseases, such as metabolic syndrome, type 2 diabetes mellitus, and cardiovascular diseases. The inbred C57BL/6 mouse strain is often used for various experimental investigations, such as metabolic research. However, over time, genetically distinguishable C57BL/6 substrains have evolved. The manifestation of genetic alterations has resulted in behavioral and metabolic differences. In this study, a comparison of diet-induced obesity in C57BL/6JHanZtm, C57BL/6NCrl and C57BL/6 J mice revealed several metabolic and immunological differences such as blood glucose level and cytokine expression, respectively, among these C57BL/6 substrains. For example, C57BL/6NCrl mice developed the most pronounced adiposity, whereas C57BL/6 J mice showed the highest impairment in glucose tolerance. Moreover, our results indicated that the immunological phenotype depends on the intestinal microbiota, as the cell subset composition of the colon was similar in obese ex-GF B6NRjB6JHanZtm and obese B6JHanZtm mice. Phenotypic differences between C57BL/6 substrains are caused by a complex combination of genetic and microbial alterations. Therefore, in performing metabolic research, considering substrain-specific characteristics, which can influence the course of study, is important. Moreover, for unbiased comparison of data, the entire strain name should be shared with the scientific community.


Assuntos
Microbioma Gastrointestinal , Genótipo , Obesidade/genética , Fenótipo , Animais , Dieta Hiperlipídica/efeitos adversos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/etiologia , Obesidade/microbiologia , Obesidade/patologia
17.
Am J Physiol Endocrinol Metab ; 318(6): E965-E980, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32228321

RESUMO

Blueberry consumption can prevent obesity-linked metabolic diseases, and it has been proposed that the polyphenol content of blueberries may contribute to these effects. Polyphenols have been shown to favorably impact metabolic health, but the role of specific polyphenol classes and whether the gut microbiota is linked to these effects remain unclear. We aimed to evaluate the impact of whole blueberry powder and blueberry polyphenols on the development of obesity and insulin resistance and to determine the potential role of gut microbes in these effects by using fecal microbiota transplantation (FMT). Sixty-eight C57BL/6 male mice were assigned to one of the following diets for 12 wk: balanced diet (Chow); high-fat, high-sucrose diet (HFHS); or HFHS supplemented with whole blueberry powder (BB), anthocyanidin (ANT)-rich extract, or proanthocyanidin (PAC)-rich extract. After 8 wk, mice were housed in metabolic cages, and an oral glucose tolerance test (OGTT) was performed. Sixty germ-free mice fed HFHS diet received FMT from one of the above groups biweekly for 8 wk, followed by an OGTT. PAC-treated mice were leaner than HFHS controls although they had the same energy intake and were more physically active. This observation was reproduced in germ-free mice receiving FMT from PAC-treated mice. PAC- and ANT-treated mice showed improved insulin responses during OGTT, and this finding was also reproduced in germ-free mice following FMT. These results show that blueberry PAC and ANT polyphenols can reduce diet-induced body weight and improve insulin sensitivity and that at least part of these beneficial effects are explained by modulation of the gut microbiota.


Assuntos
Antocianinas/farmacologia , Mirtilos Azuis (Planta) , Frutas , Microbioma Gastrointestinal/efeitos dos fármacos , Resistência à Insulina , Obesidade/metabolismo , Extratos Vegetais/farmacologia , Proantocianidinas/farmacologia , Animais , Peso Corporal/efeitos dos fármacos , Dieta Hiperlipídica , Sacarose na Dieta , Transplante de Microbiota Fecal , Teste de Tolerância a Glucose , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/microbiologia
18.
BMC Vet Res ; 16(1): 78, 2020 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-32131835

RESUMO

BACKGROUND: Obesity is an important equine welfare issue. Whilst dietary restriction is the most effective weight-loss tool, individual animals range in their weight-loss propensity. Gastrointestinal-derived bacteria play a fundamental role in host-health and have been associated with obesity and weight-loss in other species. This study evaluated the faecal microbiome (next-generation sequencing of 16S rRNA genes) of 15 obese Welsh Mountain pony mares, in the same 11-week period across 2 years (n = 8 Year 1; n = 7 Year 2). Following a 4-week acclimation period (pre-diet phase) during which time individuals were fed the same hay to maintenance (2% body mass (BM) as daily dry matter (DM) intake), animals underwent a 7-week period of dietary restriction (1% BM hay as daily DM intake). Faeces were sampled on the final 3 days of the pre-diet phase and the final 3 days of the dietary restriction phase. Bacterial communities were determined using Next Generation Sequencing of amplified V1-V2 hypervariable regions of bacterial 16S rRNA. RESULTS: Losses in body mass ranged from 7.11 to 11.59%. Changes in the faecal microbiome composition following weight-loss included a reduction in the relative abundance of Firmicutes and Tenericutes and a reduction in indices of bacterial diversity. Pre-diet diversity was negatively associated with weight-loss. Pre-diet faecal acetate concentration was a strong predictor of subsequent weight-loss and negatively associated with Sphaerochaeta (Spirochaetes phylum) abundance. When animals were divided into 3 groups (high, mid, low) based overall weight loss, pre-diet bacterial community structure was found to have the greatest divergence between the high and low weight-loss groups (R = 0.67, p <  0.01), following PERMANOVA and ANOSIM analysis. CONCLUSIONS: Weight-loss in this group of ponies was associated with lower pre-diet faecal bacterial diversity and greater pre-diet acetate concentration. Overall, these data support a role for the faecal microbiome in weight-loss propensity in ponies and provide a baseline for research evaluating elements of the faecal microbiome in predicting weight-loss success in larger cohorts.


Assuntos
Microbioma Gastrointestinal , Cavalos/microbiologia , Obesidade/veterinária , Perda de Peso/fisiologia , Acetatos/análise , Animais , Dieta/veterinária , Fezes/química , Fezes/microbiologia , Feminino , Cavalos/fisiologia , Obesidade/microbiologia , RNA Ribossômico 16S
19.
Artigo em Inglês | MEDLINE | ID: mdl-32152146

RESUMO

OBJECTIVE: Obesity is associated with metabolic abnormalities, including insulin resistance and dyslipidemias. Previous studies demonstrated that genistein intake modifies the gut microbiota in mice by selectively increasing Akkermansia muciniphila, leading to reduction of metabolic endotoxemia and insulin sensitivity. However, it is not known whether the consumption of genistein in humans with obesity could modify the gut microbiota reducing the metabolic endotoxemia and insulin sensitivity. RESEARCH DESIGN AND METHODS: 45 participants with a Homeostatic Model Assessment (HOMA) index greater than 2.5 and body mass indices of ≥30 and≤40 kg/m2 were studied. Patients were randomly distributed to consume (1) placebo treatment or (2) genistein capsules (50 mg/day) for 2 months. Blood samples were taken to evaluate glucose concentration, lipid profile and serum insulin. Insulin resistance was determined by means of the HOMA for insulin resistance (HOMA-IR) index and by an oral glucose tolerance test. After 2 months, the same variables were assessed including a serum metabolomic analysis, gut microbiota, and a skeletal muscle biopsy was obtained to study the gene expression of fatty acid oxidation. RESULTS: In the present study, we show that the consumption of genistein for 2 months reduced insulin resistance in subjects with obesity, accompanied by a modification of the gut microbiota taxonomy, particularly by an increase in the Verrucomicrobia phylum. In addition, subjects showed a reduction in metabolic endotoxemia and an increase in 5'-adenosine monophosphate-activated protein kinase phosphorylation and expression of genes involved in fatty acid oxidation in skeletal muscle. As a result, there was an increase in circulating metabolites of ß-oxidation and ω-oxidation, acyl-carnitines and ketone bodies. CONCLUSIONS: Change in the gut microbiota was accompanied by an improvement in insulin resistance and an increase in skeletal muscle fatty acid oxidation. Therefore, genistein could be used as a part of dietary strategies to control the abnormalities associated with obesity, particularly insulin resistance; however, long-term studies are needed.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Fármacos Antiobesidade/administração & dosagem , Microbioma Gastrointestinal/efeitos dos fármacos , Genisteína/administração & dosagem , Resistência à Insulina , Músculo Esquelético/efeitos dos fármacos , Obesidade/metabolismo , Obesidade/microbiologia , Método Duplo-Cego , Ácidos Graxos/metabolismo , Humanos , Músculo Esquelético/metabolismo
20.
Sci Rep ; 10(1): 4183, 2020 03 06.
Artigo em Inglês | MEDLINE | ID: mdl-32144319

RESUMO

In an exploratory, block-randomised, parallel, double-blind, single-centre, placebo-controlled superiority study (ISRCTN12562026, funded by Cultech Ltd), 220 Bulgarian participants (30 to 65 years old) with BMI 25-34.9 kg/m2 received Lab4P probiotic (50 billion/day) or a matched placebo for 6 months. Participants maintained their normal diet and lifestyle. Primary outcomes were changes in body weight, BMI, waist circumference (WC), waist-to-height ratio (WtHR), blood pressure and plasma lipids. Secondary outcomes were changes in plasma C-reactive protein (CRP), the diversity of the faecal microbiota, quality of life (QoL) assessments and the incidence of upper respiratory tract infection (URTI). Significant between group decreases in body weight (1.3 kg, p < 0.0001), BMI (0.045 kg/m2, p < 0.0001), WC (0.94 cm, p < 0.0001) and WtHR (0.006, p < 0.0001) were in favour of the probiotic. Stratification identified greater body weight reductions in overweight subjects (1.88%, p < 0.0001) and in females (1.62%, p = 0.0005). Greatest weight losses were among probiotic hypercholesterolaemic participants (-2.5%, p < 0.0001) alongside a significant between group reduction in small dense LDL-cholesterol (0.2 mmol/L, p = 0.0241). Improvements in QoL and the incidence rate ratio of URTI (0.60, p < 0.0001) were recorded for the probiotic group. No adverse events were recorded. Six months supplementation with Lab4P probiotic resulted in significant weight reduction and improved small dense low-density lipoprotein-cholesterol (sdLDL-C) profiles, QoL and URTI incidence outcomes in overweight/obese individuals.


Assuntos
Bifidobacterium/fisiologia , Lactobacillus/fisiologia , Obesidade/tratamento farmacológico , Obesidade/microbiologia , Sobrepeso/tratamento farmacológico , Sobrepeso/microbiologia , Probióticos/uso terapêutico , Peso Corporal/fisiologia , Método Duplo-Cego , Feminino , Humanos , Masculino , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Infecções Respiratórias , Circunferência da Cintura/fisiologia , Perda de Peso/fisiologia
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