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1.
Microbiol Spectr ; 9(1): e0053621, 2021 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-34378965

RESUMO

Transmission of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in millions of deaths and declining economies around the world. K18-hACE2 mice develop disease resembling severe SARS-CoV-2 infection in a virus dose-dependent manner. The relationship between SARS-CoV-2 and the intestinal or respiratory microbiome is not fully understood. In this context, we characterized the cecal and lung microbiomes of SARS-CoV-2-challenged K18-hACE2 transgenic mice in the presence or absence of treatment with the Mpro inhibitor GC-376. Cecum microbiome showed decreased Shannon and inverse (Inv) Simpson diversity indexes correlating with SARS-CoV-2 infection dosage and a difference of Bray-Curtis dissimilarity distances among control and infected mice. Bacterial phyla such as Firmicutes, particularly, Lachnospiraceae and Oscillospiraceae, were significantly less abundant, while Verrucomicrobia, particularly, the family Akkermansiaceae, were increasingly more prevalent during peak infection in mice challenged with a high virus dose. In contrast to the cecal microbiome, the lung microbiome showed similar microbial diversity among the control, low-, and high-dose challenge virus groups, independent of antiviral treatment. Bacterial phyla in the lungs such as Bacteroidetes decreased, while Firmicutes and Proteobacteria were significantly enriched in mice challenged with a high dose of SARS-CoV-2. In summary, we identified changes in the cecal and lung microbiomes of K18-hACE2 mice with severe clinical signs of SARS-CoV-2 infection. IMPORTANCE The COVID-19 pandemic has resulted in millions of deaths. The host's respiratory and intestinal microbiome can affect directly or indirectly the immune system during viral infections. We characterized the cecal and lung microbiomes in a relevant mouse model challenged with a low or high dose of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the presence or absence of an antiviral Mpro inhibitor, GC-376. Decreased microbial diversity and taxonomic abundances of the phyla Firmicutes, particularly, Lachnospiraceae, correlating with infection dosage were observed in the cecum. In addition, microbes within the family Akkermansiaceae were increasingly more prevalent during peak infection, which is observed in other viral infections. The lung microbiome showed similar microbial diversity to that of the control, independent of antiviral treatment. Decreased Bacteroidetes and increased Firmicutes and Proteobacteria were observed in the lungs in a virus dose-dependent manner. These studies add to a better understanding of the complexities associated with the intestinal microbiome during respiratory infections.


Assuntos
COVID-19/imunologia , COVID-19/microbiologia , Microbioma Gastrointestinal/fisiologia , SARS-CoV-2 , Enzima de Conversão de Angiotensina 2 , Animais , Antivirais , Biodiversidade , Modelos Animais de Doenças , Feminino , Pulmão/imunologia , Melfalan , Camundongos , Camundongos Transgênicos , Viroses/imunologia , gama-Globulinas
2.
Nutrients ; 13(8)2021 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-34444909

RESUMO

Glucosinolates (GLS) and their derivatives are secondary plant metabolites abundant in Brassicaceae. Due to the enzymatic reaction between GLS and myrosinase enzyme, characteristic compounds with a pungent taste are formed, used by plants to defend themselves against insect herbivores. These GLS derivatives have an important impact on human health, including anti-inflammation and anti-cancer effects. However, GLS derivatives' formation needs previous enzymatic reactions catalyzed by myrosinase enzyme. Many of the brassica-based foods are processed at a high temperature that inactivates enzymes, hindering its bioavailability. In the last decade, several studies showed that the human gut microbiome can provide myrosinase activity that potentially can raise the beneficial effects of consumption of vegetables rich in GLS. The variability of the human gut microbiome (HGM) in human populations and the diverse intake of GLS through the diet may lead to greater variability of the real dose of pro-healthy compounds absorbed by the human body. The exploitation of the genetic and biochemical potential of HGM and correct ecological studies of both isolated strains and mixed population are of great interest. This review focuses on the most recent advances in this field.


Assuntos
Brassica/química , Microbioma Gastrointestinal/fisiologia , Glucosinolatos/metabolismo , Anti-Inflamatórios/farmacocinética , Antineoplásicos/farmacocinética , Disponibilidade Biológica , Manipulação de Alimentos , Glicosídeo Hidrolases/metabolismo , Temperatura Alta/efeitos adversos , Humanos , Paladar , Verduras/química
3.
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
4.
Nutrients ; 13(8)2021 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-34444848

RESUMO

Flavonoids are a major group of dietary plant polyphenols and have a positive health impact, but their modification and degradation in the human gut is still widely unknown. Due to the rise of metagenome data of the human gut microbiome and the assembly of hundreds of thousands of bacterial metagenome-assembled genomes (MAGs), large-scale screening for potential flavonoid-modifying enzymes of human gut bacteria is now feasible. With sequences of characterized flavonoid-transforming enzymes as queries, the Unified Human Gastrointestinal Protein catalog was analyzed and genes encoding putative flavonoid-modifying enzymes were quantified. The results revealed that flavonoid-modifying enzymes are often encoded in gut bacteria hitherto not considered to modify flavonoids. The enzymes for the physiologically important daidzein-to-equol conversion, well studied in Slackiaisoflavoniconvertens, were encoded only to a minor extent in Slackia MAGs, but were more abundant in Adlercreutzia equolifaciens and an uncharacterized Eggerthellaceae species. In addition, enzymes with a sequence identity of about 35% were encoded in highly abundant MAGs of uncultivated Collinsella species, which suggests a hitherto uncharacterized daidzein-to-equol potential in these bacteria. Of all potential flavonoid modification steps, O-deglycosylation (including derhamnosylation) was by far the most abundant in this analysis. In contrast, enzymes putatively involved in C-deglycosylation were detected less often in human gut bacteria and mainly found in Agathobacter faecis (formerly Roseburia faecis). Homologs to phloretin hydrolase, flavanonol/flavanone-cleaving reductase and flavone reductase were of intermediate abundance (several hundred MAGs) and mainly prevalent in Flavonifractor plautii. This first comprehensive insight into the black box of flavonoid modification in the human gut highlights many hitherto overlooked and uncultured bacterial genera and species as potential key organisms in flavonoid modification. This could lead to a significant contribution to future biochemical-microbiological investigations on gut bacterial flavonoid transformation. In addition, our results are important for individual nutritional recommendations and for biotechnological applications that rely on novel enzymes catalyzing potentially useful flavonoid modification reactions.


Assuntos
Proteínas de Bactérias/metabolismo , Flavonoides/metabolismo , Microbioma Gastrointestinal/fisiologia , Fenômenos Fisiológicos da Nutrição/fisiologia , Simulação por Computador , Equol/metabolismo , Genoma Bacteriano , Humanos , Isoflavonas/metabolismo , Metagenoma , Peptídeo Hidrolases/metabolismo , Proteólise
5.
Nutrients ; 13(8)2021 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-34444852

RESUMO

We aimed to observe the combined effects of Gaussian graphical model (GGM)-derived dietary patterns and the gastric microbiome on the risk of gastric cancer (GC) in a Korean population. The study included 268 patients with GC and 288 healthy controls. Food intake was assessed using a 106-item semiquantitative food frequency questionnaire. GGMs were applied to derive dietary pattern networks. 16S rRNA gene sequencing was performed using DNA extracted from gastric biopsy samples. The fruit pattern network was inversely associated with the risk of GC for the highest vs. lowest tertiles in the total population (odds ratio (OR): 0.47; 95% confidence interval (CI): 0.28-0.77; p for trend = 0.003) and in females (OR: 0.38; 95% CI: 0.17-0.83; p for trend = 0.021). Males who had a low microbial dysbiosis index (MDI) and high vegetable and seafood pattern score showed a significantly reduced risk of GC (OR: 0.44; 95% CI: 0.22-0.91; p-interaction = 0.021). Females who had a low MDI and high dairy pattern score showed a significantly reduced risk of GC (OR: 0.23; 95% CI: 0.07-0.76; p-interaction = 0.018). Our novel findings revealed that vegetable and seafood pattern might interact with dysbiosis to attenuate the risk of GC in males, whereas the dairy pattern might interact with dysbiosis to reduce the GC risk in females.


Assuntos
Dieta/efeitos adversos , Dieta/estatística & dados numéricos , Microbioma Gastrointestinal/fisiologia , Neoplasias Gástricas/etiologia , Estômago/microbiologia , Estudos de Casos e Controles , Inquéritos sobre Dietas , Disbiose/complicações , Disbiose/fisiopatologia , Ingestão de Alimentos/fisiologia , Feminino , Frutas , Humanos , Masculino , Pessoa de Meia-Idade , RNA Ribossômico 16S/análise , República da Coreia/epidemiologia , Fatores de Risco , Fatores Sexuais , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/microbiologia , Verduras
6.
Nutrients ; 13(8)2021 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-34444890

RESUMO

Obesity prevention interventions generally have either not worked or had effects inadequate to mitigate the problem. They have been predicated on the simple energy balance model, which has been severely questioned by biological scientists. Numerous other etiological mechanisms have been proposed, including the intestinal microbiome, which has been related to childhood obesity in numerous ways. Public health research is needed in regard to diet and the microbiome, which hopefully will lead to effective child obesity prevention.


Assuntos
Dieta Saudável/métodos , Ingestão de Alimentos/fisiologia , Metabolismo Energético/fisiologia , Microbioma Gastrointestinal/fisiologia , Obesidade Pediátrica/prevenção & controle , Criança , Feminino , Homeostase/fisiologia , Humanos , Masculino
7.
Int J Mol Sci ; 22(16)2021 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-34445800

RESUMO

Inflammatory bowel disease is a chronic, idiopathic and complex condition, which most often manifests itself in the form of ulcerative colitis or Crohn's disease. Both forms are associated with dysregulation of the mucosal immune system, compromised intestinal epithelial barrier, and dysbiosis of the gut microbiome. It has been observed for a long time that bile acids are involved in inflammatory disorders, and recent studies show their significant physiological role, reaching far beyond being emulsifiers helping in digestion of lipids. Bile acids are also signaling molecules, which act, among other things, on lipid metabolism and immune responses, through several nuclear and membrane receptors in hepatocytes, enterocytes and cells of the immune system. Gut microbiota homeostasis also seems to be affected, directly and indirectly, by bile acid metabolism and signaling. This review summarizes recent advances in the field of bile acid signaling, studies of inflamed gut microbiome, and the therapeutic potential of bile acids in the context of inflammatory bowel disease.


Assuntos
Ácidos e Sais Biliares/metabolismo , Doenças Inflamatórias Intestinais/metabolismo , Transdução de Sinais/fisiologia , Animais , Microbioma Gastrointestinal/fisiologia , Humanos , Sistema Imunitário/metabolismo
8.
Anim Sci J ; 92(1)2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34405934

RESUMO

The methane-mitigating potency of cashew nutshell liquid (CNSL) was evaluated by investigating gas production from batch cultures using feces from Thai native ruminants that had been incubated for different periods. Feces was obtained from four Thai native cattle and four swamp buffaloes reared under practical feeding conditions at the Kasetsart University farm, Thailand. Fecal slurry from the same farm was also included in the analysis. CNSL addition successfully suppressed the methane production potential of feces from both ruminants by shifting short chain fatty acid profiles towards propionate production. Methane mitigation continued for almost 150 days, although the degree of mitigation was more apparent from Day 0 to Day 30. Bacterial and archaeal community shifts with CNSL addition were observed in feces from both ruminants; specifically, Bacteroides increased, whereas Lachnospiraceae and Ruminococcaceae decreased in feces to which CNSL was added. Fecal slurry did not show marked changes in gas production with CNSL addition. The findings showed that the addition of CNSL to the feces of ruminants native to the Southeast Asian region can suppress methane emission. Because CNSL can be easily obtained as a byproduct of the local cashew industry in this region, its on-site application might be ideal.


Assuntos
Anacardium/química , Fezes/microbiologia , Gases/metabolismo , Microbioma Gastrointestinal/fisiologia , Metano/metabolismo , Extratos Vegetais/farmacologia , Animais , Búfalos , Bovinos , Ácidos Graxos Voláteis/metabolismo , Fezes/química , Microbiota , Propionatos/metabolismo , Tailândia
9.
Nutrients ; 13(8)2021 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-34444955

RESUMO

Diet and dietary components have profound effects on the composition of the gut microbiota and are among the most important contributors to the alteration in bacterial flora. This review examines the effects the "Western", "plant-based", "high-fat", "medical ketogenic", and "Mediterranean" diets have on the composition of the gut microbiota in both mice and human subjects. We show that specific dietary components that are commonly found in the "plant-based" and "Mediterranean" diet play a role in shifting the microbial composition. This review further evaluates the bacterial metabolites that are associated with diet, and their role in systemic inflammation and metabolic endotoxemia. Furthermore, the associations between diet/dietary components and altering bacterial composition, may lead to potential therapeutic targets for type II diabetes, obesity, and inflammatory diseases.


Assuntos
Dieta/efeitos adversos , Microbioma Gastrointestinal/fisiologia , Fenômenos Fisiológicos da Nutrição , Animais , Dieta/métodos , Dieta Hiperlipídica/efeitos adversos , Dieta Cetogênica/efeitos adversos , Dieta Mediterrânea/efeitos adversos , Dieta Vegetariana/efeitos adversos , Dieta Ocidental/efeitos adversos , Endotoxemia/etiologia , Endotoxemia/microbiologia , Humanos , Inflamação/etiologia , Inflamação/microbiologia , Camundongos
10.
Nutrients ; 13(7)2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34371800

RESUMO

Cardiovascular diseases (CVDs) can originate from early life. Accumulating evidence suggests that gut microbiota in early life is linked to CVDs in later life. Gut microbiota-targeted therapy has gained significant importance in recent decades for its health-promoting role in the prevention (rather than just treatment) of CVDs. Thus far, available gut microbiota-based treatment modalities used as reprogramming interventions include probiotics, prebiotics, and postbiotics. The purpose of this review is, first, to highlight current studies that link dysbiotic gut microbiota to the developmental origins of CVD. This is followed by a summary of the connections between the gut microbiota and CVD behind cardiovascular programming, such as short chain fatty acids (SCFAs) and their receptors, trimethylamine-N-oxide (TMAO), uremic toxins, and aryl hydrocarbon receptor (AhR), and the renin-angiotensin system (RAS). This review also presents an overview of how gut microbiota-targeted reprogramming interventions can prevent the developmental origins of CVD from animal studies. Overall, this review reveals that recent advances in gut microbiota-targeted therapy might provide the answers to reduce the global burden of CVDs. Still, additional studies will be needed to put research findings into practice.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Disbiose/prevenção & controle , Microbioma Gastrointestinal/fisiologia , Terapia Nutricional/métodos , Probióticos/uso terapêutico , Animais , Doenças Cardiovasculares/microbiologia , Disbiose/microbiologia , Humanos , Fenômenos Fisiológicos da Nutrição , Prebióticos/administração & dosagem
11.
Nat Commun ; 12(1): 4725, 2021 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-34354051

RESUMO

Gut microbiota deficient mice demonstrate accelerated glucose clearance. However, which tissues are responsible for the upregulated glucose uptake remains unresolved, with different studies suggesting that browning of white adipose tissue, or modulated hepatic gluconeogenesis, may be related to enhanced glucose clearance when the gut microbiota is absent. Here, we investigate glucose uptake in 22 different tissues in 3 different mouse models. We find that gut microbiota depletion via treatment with antibiotic cocktails (ABX) promotes glucose uptake in brown adipose tissue (BAT) and cecum. Nevertheless, the adaptive thermogenesis and the expression of uncoupling protein 1 (UCP1) are dispensable for the increased glucose uptake and clearance. Deletion of Ucp1 expressing cells blunts the improvement of glucose clearance in ABX-treated mice. Our results indicate that BAT and cecum, but not white adipose tissue (WAT) or liver, contribute to the glucose uptake in the gut microbiota depleted mouse model and this response is dissociated from adaptive thermogenesis.


Assuntos
Tecido Adiposo Marrom/metabolismo , Microbioma Gastrointestinal/fisiologia , Glucose/metabolismo , Adipócitos Bege/metabolismo , Adipócitos Marrons/metabolismo , Tecido Adiposo Branco/metabolismo , Animais , Antibacterianos/administração & dosagem , Ceco/metabolismo , Dieta Hiperlipídica/efeitos adversos , Microbioma Gastrointestinal/efeitos dos fármacos , Vida Livre de Germes , Masculino , Camundongos , Camundongos Knockout , Obesidade/metabolismo , Obesidade/patologia , Termogênese/fisiologia , Proteína Desacopladora 1/deficiência , Proteína Desacopladora 1/genética , Proteína Desacopladora 1/metabolismo
12.
Nat Commun ; 12(1): 4728, 2021 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-34354065

RESUMO

Understanding how diet and gut microbiota interact in the context of human health is a key question in personalized nutrition. Genome-scale metabolic networks and constraint-based modeling approaches are promising to systematically address this complex problem. However, when applied to nutritional questions, a major issue in existing reconstructions is the limited information about compounds in the diet that are metabolized by the gut microbiota. Here, we present AGREDA, an extended reconstruction of diet metabolism in the human gut microbiota. AGREDA adds the degradation pathways of 209 compounds present in the human diet, mainly phenolic compounds, a family of metabolites highly relevant for human health and nutrition. We show that AGREDA outperforms existing reconstructions in predicting diet-specific output metabolites from the gut microbiota. Using 16S rRNA gene sequencing data of faecal samples from Spanish children representing different clinical conditions, we illustrate the potential of AGREDA to establish relevant metabolic interactions between diet and gut microbiota.


Assuntos
Dieta , Microbioma Gastrointestinal/fisiologia , Redes e Vias Metabólicas , Modelos Biológicos , Algoritmos , Criança , Fenômenos Fisiológicos da Nutrição Infantil , Dieta Mediterrânea , Fermentação , Microbioma Gastrointestinal/genética , Humanos , Técnicas In Vitro , Lens (Planta)/química , Valor Nutritivo , RNA Ribossômico 16S/genética , Espanha
13.
Hawaii J Health Soc Welf ; 80(8): 195-198, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34355196

RESUMO

Native Hawaiian and Pacific Islander (NHPI) populations suffer from disproportionately higher rates of chronic conditions, such as type 2 diabetes, that arises from metabolic dysfunction and are often associated with obesity and inflammation. In addition, the global coronavirus disease 2019 pandemic has further compounded the effect of health inequities observed in Indigenous populations, including NHPI communities. Reversible lifestyle habits, such as diet, may either be protective of or contribute to the increasing prevalence of health inequities in these populations via the immunoepigenetic-microbiome axis. This axis offers insight into the connection between diet, epigenetics, the microbiome composition, immune function, and response to viral infection. Epigenetic mechanisms that regulate inflammatory states associated with metabolic diseases, including diabetes, are impacted by diet. Furthermore, diet may modulate the gut microbiome by influencing microbial diversity and richness; dysbiosis of the microbiome is associated with chronic disease. A high fiber diet facilitates a favorable microbiome composition and in turn increases production of intermediate metabolites named short-chain fatty acids (SCFAs) that act on metabolic and immune pathways. In contrast, low fiber diets typically associated with a westernized lifestyle decreases the abundance of microbial derived SCFAs. This decreased abundance is characteristic of metabolic syndromes and activation of chronic inflammatory states, having larger implications in disease pathogenesis of both communicable and non-communicable diseases. Native Hawaiians and Pacific Islanders that once thrived on healthy traditional diets may be more sensitive than non-indigenous peoples to the metabolic perturbation of westernized diets that impinge on the immunoepigenetic-gut microbiome axis. Recent studies conducted in the Maunakea lab at the University of Hawai'i at Manoa John A. Burns School of Medicine have helped elucidate the connections between diet, microbiome composition, metabolic syndrome, and epigenetic regulation of immune function to better understand disease pathogenesis. Potentially, this research could point to ways to prevent pre-disease conditions through novel biomarker discovery using community-based approaches.


Assuntos
Dieta/métodos , Epigênese Genética/fisiologia , Microbioma Gastrointestinal/fisiologia , Disparidades nos Níveis de Saúde , Imunidade/fisiologia , Grupo com Ancestrais Oceânicos , Pesquisa Biomédica , Diabetes Mellitus Tipo 2/etnologia , Diabetes Mellitus Tipo 2/fisiopatologia , Fibras na Dieta/farmacologia , Ácidos Graxos Voláteis/fisiologia , Hawaii/epidemiologia , Humanos , Mediadores da Inflamação/fisiologia
14.
Nat Commun ; 12(1): 4845, 2021 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-34381036

RESUMO

The human gut microbiota is increasingly recognized as an important factor in modulating innate and adaptive immunity through release of ligands and metabolites that translocate into circulation. Urbanizing African populations harbor large intestinal diversity due to a range of lifestyles, providing the necessary variation to gauge immunomodulatory factors. Here, we uncover a gradient of intestinal microbial compositions from rural through urban Tanzanian, towards European samples, manifested both in relative abundance and genomic variation observed in stool metagenomics. The rural population shows increased Bacteroidetes, led by Prevotella copri, but also presence of fungi. Measured ex vivo cytokine responses were significantly associated with 34 immunomodulatory microbes, which have a larger impact on circulating metabolites than non-significant microbes. Pathway effects on cytokines, notably TNF-α and IFN-γ, differential metabolome analysis and enzyme copy number enrichment converge on histidine and arginine metabolism as potential immunomodulatory pathways mediated by Bifidobacterium longum and Akkermansia muciniphila.


Assuntos
Citocinas/imunologia , Microbioma Gastrointestinal/fisiologia , População Rural , População Urbana , Adulto , Arginina/metabolismo , Bactérias/imunologia , Bactérias/isolamento & purificação , Bactérias/metabolismo , Dieta , Feminino , Microbioma Gastrointestinal/imunologia , Histidina/metabolismo , Humanos , Imunomodulação , Masculino , Redes e Vias Metabólicas , Metaboloma/imunologia , Fatores Socioeconômicos , Tanzânia , Urbanização
15.
Int J Mol Sci ; 22(15)2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34360839

RESUMO

Hypercholesterolemia plays a causal role in the development of atherosclerosis and is one of the main risk factors for cardiovascular disease (CVD), the leading cause of death worldwide especially in developed countries. Current data show that the role of microbiota extends beyond digestion by being implicated in several metabolic and inflammatory processes linked to several diseases including CVD. Studies have reported associations between bacterial metabolites and hypercholesterolemia. However, such associations remain poorly investigated and characterized. In this review, the mechanisms of microbial derived metabolites such as primary and secondary bile acids (BAs), trimethylamine N-oxide (TMAO), and short-chain fatty acids (SCFAs) will be explored in the context of cholesterol metabolism. These metabolites play critical roles in maintaining cardiovascular health and if dysregulated can potentially contribute to CVD. They can be modulated via nutritional and pharmacological interventions such as statins, prebiotics, and probiotics. However, the mechanisms behind these interactions also remain unclear, and mechanistic insights into their impact will be provided. Therefore, the objectives of this paper are to present current knowledge on potential mechanisms whereby microbial metabolites regulate cholesterol homeostasis and to discuss the feasibility of modulating intestinal microbes and metabolites as a novel therapeutic for hypercholesterolemia.


Assuntos
Aterosclerose/metabolismo , Colesterol/metabolismo , Microbioma Gastrointestinal/fisiologia , Animais , Aterosclerose/microbiologia , Humanos , Hipercolesterolemia
16.
Medicine (Baltimore) ; 100(34): e27048, 2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34449492

RESUMO

ABSTRACT: Synchronous non-alcoholic fatty liver disease (NAFLD) and carotid artery plaque formation increase the risk of mortality in patients with cardiovascular disease (CVD). Metabolic status and host gut flora are associated with NAFLD and CVD, but the risk factors require further evaluation.To evaluate the risk factors associated with NAFLD and CVD, including gut-flora-related examinations.This cross-sectional study included 235 subjects aged over 40 years who underwent abdominal ultrasound examination and carotid artery ultrasound examination on the same day or within 12 months of abdominal ultrasound between January 2018 and December 2019. All subjects underwent blood tests, including endotoxin and trimethylamine-N-oxide.The synchronous NAFLD and carotid artery plaque subjects had a higher proportion of men and increased age compared with those without NAFLD and no carotid artery plaque. The synchronous NAFLD and carotid artery plaque group had increased body mass index (BMI), blood pressure, hemoglobin A1C (5.71% vs 5.42%), triglyceride (TG) (164.61 mg/dL vs 102.61 mg/dL), and low-density lipoprotein (135.27 mg/dL vs 121.42 mg/dL). In multiple logistic regression analysis, increased BMI, mean systolic blood pressure, and TG > 110 mg/dL were independent risk factors for synchronous NAFLD and carotid artery plaque formation. Endotoxin and trimethylamine-N-oxide levels were not significantly different between the 2 groups.Host metabolic status, such as elevated BMI, TG, and systolic blood pressure, are associated with synchronous NAFLD and carotid artery plaque in asymptomatic adults. Aggressive TG control, blood pressure control, and weight reduction are indicated in patients with NAFLD.


Assuntos
Estenose das Carótidas/epidemiologia , Estenose das Carótidas/fisiopatologia , Microbioma Gastrointestinal/fisiologia , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/fisiopatologia , Adulto , Fatores Etários , Pressão Sanguínea , Índice de Massa Corporal , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/fisiopatologia , Estudos Transversais , Hemoglobina A Glicada , Humanos , Lipídeos/sangue , Pessoa de Meia-Idade , Fatores Sexuais
17.
Nutrients ; 13(7)2021 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-34371979

RESUMO

Grape pomace (GP) is a winemaking by-product rich in polyphenols and fibre. Supplementation with GP extracts has shown potential benefits against oxidative stress- and inflammation-related pathologies. As a new nutritional target, this paper explores the impact of the ingestion of a grape pomace extract on intestinal barrier functionality. A GP extract was sequentially subjected to gastrointestinal and colonic digestion using the dynamic gastrointestinal simulator (simgi®). This generated two simulated fluids: intestinal-digested extract (IDE) and colonic-digested extract (CDE). The effects of these two fluids on paracellular permeability and the expression of tight junction (TJ) proteins (i.e., zonula occludens-1 (ZO-1) and occludin) were assessed in Caco-2-cell monolayers grown in Transwell® inserts. The IDE fluid significantly (p < 0.001) reduced the paracellular transport of FITC-dextran with respect to the control, whereas no significant differences (p > 0.05) were found for CDE, which could be due, at least partially, to the pro-leaky effect of the colonic digestion medium. Accordant slight increases in the mRNA levels of both ZO-1 and occludin were observed for IDE, but without statistical significance. Additionally, the colonic fermentation of the GP extract promoted the production of short-chain fatty acids (SCFA) and phenolic metabolites and led to changes in the relative abundance of some bacteria that might affect paracellular permeability. Overall, this paper reports first trends about the effects of grape pomace extracts on intestinal permeability that would require further confirmation in future experiments.


Assuntos
Digestão , Frutas/química , Microbioma Gastrointestinal/fisiologia , Intestinos/fisiologia , Extratos Vegetais/metabolismo , Vitis , Células CACO-2 , Permeabilidade da Membrana Celular/efeitos dos fármacos , Colo/química , Colo/metabolismo , Ácidos Graxos Voláteis/metabolismo , Fermentação , Microbioma Gastrointestinal/efeitos dos fármacos , Expressão Gênica/efeitos dos fármacos , Humanos , Ocludina/genética , Fenóis/metabolismo , Extratos Vegetais/administração & dosagem , Extratos Vegetais/farmacologia , RNA Mensageiro/análise , Proteínas de Junções Íntimas/genética , Vinho , Proteína da Zônula de Oclusão-1
18.
Nutrients ; 13(8)2021 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-34444706

RESUMO

Cranberry is a fruit originally from New England and currently growing throughout the east and northeast parts of the USA and Canada. The supplementation of cranberry extracts as nutraceuticals showed to contribute to the prevention of urinary tract infections, and most likely it may help to prevent cardiovascular and gastroenteric diseases, as highlighted by several clinical trials. However, aiming to validate the efficacy and safety of clinical applications as long-term randomized clinical trials (RCTs), further investigations of the mechanisms of action are required. In addition, a real challenge for next years is the standardization of cranberry's polyphenolic fractions. In this context, the optimization of the extraction process and downstream processing represent a key point for a reliable active principle for the formulation of a food supplement. For this reason, new non-conventional extraction methods have been developed to improve the quality of the extracts and reduce the overall costs. The aim of this survey is to describe both technologies and processes for highly active cranberry extracts as well as the effects observed in clinical studies and the respective tolerability notes.


Assuntos
Suplementos Nutricionais , Compostos Fitoquímicos , Extratos Vegetais , Vaccinium macrocarpon , Animais , Glicemia/metabolismo , Feminino , Manipulação de Alimentos , Frutas , Sucos de Frutas e Vegetais , Microbioma Gastrointestinal/fisiologia , Trato Gastrointestinal/microbiologia , Infecções por Helicobacter/dietoterapia , Helicobacter pylori , Humanos , Inflamação/prevenção & controle , Insulina/sangue , Masculino , Compostos Fitoquímicos/análise , Compostos Fitoquímicos/isolamento & purificação , Extratos Vegetais/isolamento & purificação , Polifenóis , Infecções Urinárias/dietoterapia , Infecções Urinárias/prevenção & controle , Vaccinium macrocarpon/química
19.
Nutrients ; 13(8)2021 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-34444741

RESUMO

Gut microbiota has emerged as a major metabolically active organ with critical functions in both health and disease. The trillions of microorganisms hosted by the gastrointestinal tract are involved in numerous physiological and metabolic processes including modulation of appetite and regulation of energy in the host spanning from periphery to the brain. Indeed, bacteria and their metabolic byproducts are working in concert with the host chemosensory signaling pathways to affect both short- and long-term ingestive behavior. Sensing of nutrients and taste by specialized G protein-coupled receptor cells is important in transmitting food-related signals, optimizing nutrition as well as in prevention and treatment of several diseases, notably obesity, diabetes and associated metabolic disorders. Further, bacteria metabolites interact with specialized receptors cells expressed by gut epithelium leading to taste and appetite response changes to nutrients. This review describes recent advances on the role of gut bacteria in taste perception and functions. It further discusses how intestinal dysbiosis characteristic of several pathological conditions may alter and modulate taste preference and food consumption via changes in taste receptor expression.


Assuntos
Fenômenos Fisiológicos Bacterianos , Microbioma Gastrointestinal/fisiologia , Intestinos/microbiologia , Percepção Gustatória , Animais , Antineoplásicos/uso terapêutico , Cirurgia Bariátrica , COVID-19/fisiopatologia , Dieta , Disbiose/fisiopatologia , Comportamento Alimentar , Hormônios/metabolismo , Humanos , Doenças Inflamatórias Intestinais/fisiopatologia , Neoplasias/tratamento farmacológico , Neoplasias/fisiopatologia , Receptores Acoplados a Proteínas G/metabolismo , Paladar , Papilas Gustativas/fisiologia , Receptores Toll-Like/metabolismo
20.
Science ; 373(6558)2021 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-34446580

RESUMO

The immune system has evolved in the face of microbial exposure. How maternal infection experienced at distinct developmental stages shapes the offspring immune system remains poorly understood. Here, we show that during pregnancy, maternally restricted infection can have permanent and tissue-specific impacts on offspring immunity. Mechanistically, maternal interleukin-6 produced in response to infection can directly impose epigenetic changes on fetal intestinal epithelial stem cells, leading to long-lasting impacts on intestinal immune homeostasis. As a result, offspring of previously infected dams develop enhanced protective immunity to gut infection and increased inflammation in the context of colitis. Thus, maternal infection can be coopted by the fetus to promote long-term, tissue-specific fitness, a phenomenon that may come at the cost of predisposition to inflammatory disorders.


Assuntos
Colite/imunologia , Imunidade , Interleucina-6/imunologia , Intestinos/imunologia , Complicações Infecciosas na Gravidez/imunologia , Células Th17/imunologia , Infecções por Yersinia pseudotuberculosis/imunologia , Animais , Candidíase/imunologia , Cromatina/metabolismo , Epigênese Genética , Epigenoma , Feminino , Desenvolvimento Fetal , Microbioma Gastrointestinal/imunologia , Microbioma Gastrointestinal/fisiologia , Interleucina-6/sangue , Interleucina-6/farmacologia , Mucosa Intestinal/citologia , Mucosa Intestinal/embriologia , Mucosa Intestinal/imunologia , Intestinos/embriologia , Intestinos/microbiologia , Camundongos , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Salmonelose Animal/imunologia , Células-Tronco/imunologia , Células-Tronco/fisiologia , Subpopulações de Linfócitos T/imunologia
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