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1.
J Med Microbiol ; 70(9)2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34477545

RESUMO

Introduction. Sickle cell disease (SCD) children have a high susceptibility to pneumococcal infection. For this reason, they are routinely immunized with pneumococcal vaccines and use antibiotic prophylaxis (AP).Hypothesis/Gap Statement. Yet, little is known about SCD children's gut microbiota. If antibiotic-resistant Enterobacterales may colonize people on AP, we hypothesized that SCD children on AP are colonized by resistant enterobacteria species.Objective. To evaluate the effect of continuous AP on Enterobacterales gut colonization from children with SCD.Methodology. We analysed 30 faecal swabs from SCD children on AP and 21 swabs from children without the same condition. Enterobacterales was isolated on MacConkey agar plates and identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) (bioMérieux, Marcy l'Etoile, France). We performed the antibiogram by Vitek 2 system (bioMérieux, Marcy l'Etoile, France), and the resistance genes were identified by multiplex PCR.Results. We found four different species with resistance to one or more different antibiotic types in the AP-SCD children's group: Escherichia coli, Klebsiella pneumoniae, Citrobacter freundii, and Citrobacter farmeri. Colonization by resistant E. coli was associated with AP (prevalence ratio 2.69, 95 % confidence interval [CI], 1.98-3.67, P<0.001). Strains producing extended-spectrum ß-lactamases (ESBL) were identified only in SCD children, E. coli, 4/30 (13 %), and K. pneumoniae, 2/30 (7 %). The ESBL-producing Enterobacterales were associated with penicillin G benzathine use (95 % CI, 22.91-86.71, P<0.001). CTX-M-1 was the most prevalent among ESBL-producers (3/6, 50 %), followed by CTX-M-9 (2/6, 33 %), and CTX-M-2 (1/6, 17 %).Conclusion. Resistant enterobacteria colonize SCD children on AP, and this therapy raises the chance of ESBL-producing Enterobacterales colonization. Future studies should focus on prophylactic vaccines as exclusive therapy against pneumococcal infections.


Assuntos
Anemia Falciforme/prevenção & controle , Antibacterianos/efeitos adversos , Antibioticoprofilaxia , Enterobacteriáceas Resistentes a Carbapenêmicos/efeitos dos fármacos , Infecções por Enterobacteriaceae/microbiologia , Vacinas Pneumocócicas/efeitos adversos , Adolescente , Brasil/epidemiologia , Criança , Pré-Escolar , Farmacorresistência Bacteriana Múltipla , Feminino , Microbioma Gastrointestinal/efeitos dos fármacos , Humanos , Masculino
2.
J Microbiol ; 59(9): 827-839, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34382149

RESUMO

Probiotics effectively prevent and improve metabolic diseases such as diabetes by regulating the intestinal microenvironment and gut microbiota. However, the effects of probiotics in gestational diabetes mellitus are not clear. Here, we showed that probiotic supplements significantly improved fasting blood glucose in a gestational diabetes mellitus rat model. To further understand the mechanisms of probiotics in gestational diabetes mellitus, the gut microbiota were analyzed via 16S rRNA sequencing. We found that compared with the normal pregnant group, the gestational diabetes mellitus rats had decreased diversity of gut microbiota. Moreover, probiotic supplementation restored the diversity of the gut microbiota in gestational diabetes mellitus rats, and the gut microbiota structure tended to be similar to that of normal pregnant rats. In particular, compared with gestational diabetes mellitus rats, the abundance of Firmicutes and Actinobacteria was higher after probiotic supplementation. Furthermore, activating carbohydrate metabolism and membrane transport pathways may be involved in the potential mechanisms by which probiotic supplements alleviate gestational diabetes mellitus. Overall, our results suggested that probiotic supplementation might be a novel approach to restore the gut microbiota of gestational diabetes mellitus rats and provided an experimental evidence for the use of probiotic supplements to treat gestational diabetes mellitus.


Assuntos
Diabetes Gestacional/tratamento farmacológico , Microbioma Gastrointestinal/efeitos dos fármacos , Probióticos/administração & dosagem , Animais , Bactérias/classificação , Bactérias/efeitos dos fármacos , Bactérias/genética , Bactérias/metabolismo , Metabolismo dos Carboidratos , Carboidratos , Diabetes Gestacional/metabolismo , Diabetes Gestacional/microbiologia , Suplementos Nutricionais/análise , Feminino , Masculino , Gravidez , RNA Bacteriano/genética , RNA Ribossômico 16S/genética , Ratos , Ratos Sprague-Dawley
3.
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
4.
Nat Commun ; 12(1): 4765, 2021 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-34362925

RESUMO

Antibiotic resistance genes (ARGs) are widespread among bacteria. However, not all ARGs pose serious threats to public health, highlighting the importance of identifying those that are high-risk. Here, we developed an 'omics-based' framework to evaluate ARG risk considering human-associated-enrichment, gene mobility, and host pathogenicity. Our framework classifies human-associated, mobile ARGs (3.6% of all ARGs) as the highest risk, which we further differentiate as 'current threats' (Rank I; 3%) - already present among pathogens - and 'future threats' (Rank II; 0.6%) - novel resistance emerging from non-pathogens. Our framework identified 73 'current threat' ARG families. Of these, 35 were among the 37 high-risk ARGs proposed by the World Health Organization and other literature; the remaining 38 were significantly enriched in hospital plasmids. By evaluating all pathogen genomes released since framework construction, we confirmed that ARGs that recently transferred into pathogens were significantly enriched in Rank II ('future threats'). Lastly, we applied the framework to gut microbiome genomes from fecal microbiota transplantation donors. We found that although ARGs were widespread (73% of genomes), only 8.9% of genomes contained high-risk ARGs. Our framework provides an easy-to-implement approach to identify current and future antimicrobial resistance threats, with potential clinical applications including reducing risk of microbiome-based interventions.


Assuntos
Antibacterianos/farmacologia , Farmacorresistência Bacteriana/efeitos dos fármacos , Farmacorresistência Bacteriana/genética , Bactérias/efeitos dos fármacos , Bactérias/genética , Bases de Dados Factuais , Microbioma Gastrointestinal/efeitos dos fármacos , Genes Bacterianos/efeitos dos fármacos , Genoma , Humanos , Metagenoma , Plasmídeos
5.
Nutrients ; 13(8)2021 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-34445047

RESUMO

Sargassum fusiforme alginate (SF-Alg) possess many pharmacological activities, including hypoglycemic and hypolipidemic. However, the hypoglycemic mechanisms of SF-Alg remain unclear due to its low bioavailability. In this study, we evaluated the therapeutic effect of SF-Alg on high-fat diet (HFD)/streptozotocin (STZ)-induced type 2 diabetes (T2D) mice. SF-Alg intervention was found to significantly reduce fasting blood glucose (FBG), triglycerides (TG), and total cholesterol (TC), while increasing high-density lipoprotein cholesterol (HDL-c) and improving glucose tolerance. In addition, administrating SF-Alg to diabetic mice moderately attenuated pathological changes in adipose, hepatic, and heart tissues as well as skeletal muscle, and diminished oxidative stress. To probe the underlying mechanisms, we further analyzed the gut microbiota using 16S rRNA amplicon sequencing, as well as metabolites by non-targeted metabolomics. Here, SF-Alg significantly increased some benign bacteria (Lactobacillus, Bacteroides, Akkermansia Alloprevotella, Weissella and Enterorhabdus), and significantly decreased harmful bacteria (Turicibacter and Helicobacter). Meanwhile, SF-Alg dramatically decreased branched-chain amino acids (BCAAs) and aromatic amino acids (AAAs) in the colon of T2D mice, suggesting a positive benefit of SF-Alg as an adjvant agent for T2D.


Assuntos
Alginatos/farmacologia , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/farmacologia , Sargassum/química , Animais , Glicemia/efeitos dos fármacos , Colesterol/sangue , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/etiologia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/etiologia , Dieta Hiperlipídica/efeitos adversos , Microbioma Gastrointestinal/efeitos dos fármacos , Hiperglicemia/sangue , Hiperglicemia/tratamento farmacológico , Hiperglicemia/etiologia , Camundongos , Estreptozocina , Triglicerídeos/sangue
6.
Molecules ; 26(15)2021 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-34361604

RESUMO

A novel homogeneous polysaccharide named GEP-1 was isolated and purified from Gastrodia elata (G. elata) by hot-water extraction, ethanol precipitation, and membrane separator. GEP-1, which has a molecular weight of 20.1 kDa, contains a polysaccharide framework comprised of only glucose. Methylation and NMR analysis showed that GEP-1 contained 1,3,6-linked-α-Glcp, 1,4-linked-α-Glcp, 1,4-linked-ß-Glcp and 1,4,6-linked-α-Glcp. Interestingly, GEP-1 contained citric acid and repeating p-hydroxybenzyl alcohol as one branch. Furthermore, a bioactivity test showed that GEP-1 could significantly promote the growth of Akkermansia muciniphila (A. muciniphila) and Lacticaseibacillus paracasei (L.paracasei) strains. These results implied that GEP-1 might be useful for human by modulating gut microbiota.


Assuntos
Gastrodia/química , Microbioma Gastrointestinal/efeitos dos fármacos , Extratos Vegetais/química , Polissacarídeos/farmacologia , Akkermansia/efeitos dos fármacos , Carboidratos , Carboidratos da Dieta
7.
Molecules ; 26(15)2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34361718

RESUMO

Several classes of polysaccharides have been described to have hypocholesterolemic potential, namely cholesterol bioaccessibility and bioavailability. This review will highlight the main mechanisms by which polysaccharides are known to affect cholesterol homeostasis at the intestine, namely the effect (i) of polysaccharide viscosity and its influence on cholesterol bioaccessibility; (ii) on bile salt sequestration and its dependence on the structural diversity of polysaccharides; (iii) of bio-transformations of polysaccharides and bile salts by the gut microbiota. Different quantitative structure-hypocholesterolemic activity relationships have been explored depending on the mechanism involved, and these were based on polysaccharide physicochemical properties, such as sugar composition and ramification degree, linkage type, size/molecular weight, and charge. The information gathered will support the rationalization of polysaccharides' effect on cholesterol homeostasis and highlight predictive rules towards the development of customized hypocholesterolemic functional food.


Assuntos
Anticolesterolemiantes/química , Ácidos e Sais Biliares/química , Colesterol/química , Alimento Funcional/análise , Mucosa Intestinal/metabolismo , Polissacarídeos/química , Anticolesterolemiantes/metabolismo , Anticolesterolemiantes/uso terapêutico , Ácidos e Sais Biliares/metabolismo , Disponibilidade Biológica , Biotransformação , Colesterol/metabolismo , Microbioma Gastrointestinal/efeitos dos fármacos , Microbioma Gastrointestinal/fisiologia , Homeostase/efeitos dos fármacos , Homeostase/fisiologia , Humanos , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/microbiologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Estrutura Molecular , Peso Molecular , Polissacarídeos/metabolismo , Polissacarídeos/uso terapêutico , Eletricidade Estática
8.
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
9.
Nutrients ; 13(8)2021 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-34444860

RESUMO

Cyclophosphamide (CTX) is widely applied in cancer treatment. However, the outcome is often compromised by lymphopenia, myelosuppression, and gut dysbiosis. Here, we used jujube powder to enhance CTX efficiency through nurturing gut microbiota in order to facilitate favorable metabolisms. It was observed that the oral administration of jujube powder enriched CD8+ T cells in mouse MC38 colon tumor microenvironment and increased the diversity of gut microbiota and the abundance of Bifidobacteriales, which is helpful to the production of butyrate in the cecum content. The application of jujube powder also stimulated the production of white blood cells, especially CD8+ T cells in peripheral and bone marrow, while inhibiting the growth of eosinophils in peripheral blood and the production of IL-7 and GM-CSF in serum. All these are conductive to the significant inhibition of the tumor growth, suggesting the high potential of nurturing gut microbiota with natural products for improving the efficiency of chemotherapy.


Assuntos
Antineoplásicos Alquilantes/farmacologia , Linfócitos T CD8-Positivos/efeitos dos fármacos , Neoplasias do Colo/tratamento farmacológico , Ciclofosfamida/farmacologia , Frutas , Ziziphus , Animais , Medula Óssea/metabolismo , Terapia Combinada , Modelos Animais de Doenças , Eosinofilia , Microbioma Gastrointestinal/efeitos dos fármacos , Contagem de Leucócitos , Leucócitos/efeitos dos fármacos , Camundongos , Pós , Microambiente Tumoral/efeitos dos fármacos
10.
FASEB J ; 35(9): e21777, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34403519

RESUMO

Mycobacterium bovis is the causative agent of bovine tuberculosis and also responsible for serious threat to public health. Koumiss is a fermented mare's milk product, used as traditional drink. Here, we explored the effect of koumiss on gut microbiota and the host immune response against M bovis infection. Therefore, mice were treated with koumiss and fresh mare milk for 14 days before M bovis infection and continue for 5 weeks after infection. The results showed a clear change in the intestinal flora of mice treated with koumiss, and the lungs of mice treated with koumiss showed severe edema, inflammatory infiltration, and pulmonary nodules in M bovis-infected mice. Notably, we found that the content of short-chain fatty acids was significantly lower in the koumiss-treated group compared with the control group. However, the expression of endoplasmic reticulum stress and apoptosis-related proteins in the lungs of koumiss-treated mice were significantly decreased. Collectively, these findings suggest that koumiss treatment disturb the intestinal flora of, which is associated with disease severity and the possible mechanism that induces lungs pathology. Our current findings can be exploited further to establish the "gut-lung" axis which might be a novel strategy for the control of tuberculosis.


Assuntos
Estresse do Retículo Endoplasmático/efeitos dos fármacos , Microbioma Gastrointestinal/efeitos dos fármacos , Kumis/efeitos adversos , Mycobacterium bovis/efeitos dos fármacos , Tuberculose Pulmonar/microbiologia , Tuberculose Pulmonar/patologia , Animais , Apoptose/efeitos dos fármacos , Modelos Animais de Doenças , Ácidos Graxos/análise , Fezes/química , Fezes/microbiologia , Feminino , Microbioma Gastrointestinal/imunologia , Cavalos , Pulmão/efeitos dos fármacos , Pulmão/microbiologia , Pulmão/patologia , Camundongos , Camundongos Endogâmicos BALB C , Mycobacterium bovis/imunologia , Tuberculose Pulmonar/dietoterapia , Tuberculose Pulmonar/metabolismo
11.
Int J Mol Sci ; 22(15)2021 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-34360566

RESUMO

Disruptions in the human gut microbiome have been associated with a cycle of hepatocyte injury and regeneration characteristic of chronic liver disease. Evidence suggests that the gut microbiota can promote the development of hepatocellular carcinoma through the persistence of this inflammation by inducing genetic and epigenetic changes leading to cancer. As the gut microbiome is known for its effect on host metabolism and immune response, it comes as no surprise that the gut microbiome may have a role in the response to therapeutic strategies such as immunotherapy and chemotherapy for liver cancer. Gut microbiota may influence the efficacy of immunotherapy by regulating the responses to immune checkpoint inhibitors in patients with hepatocellular carcinoma. Here, we review the mechanisms by which gut microbiota influences hepatic carcinogenesis, the immune checkpoint inhibitors currently being used to treat hepatocellular carcinoma, as well as summarize the current findings to support the potential critical role of gut microbiome in hepatocellular carcinoma (HCC) immunotherapy.


Assuntos
Carcinoma Hepatocelular/imunologia , Microbioma Gastrointestinal/efeitos dos fármacos , Imunidade , Fatores Imunológicos/uso terapêutico , Imunoterapia/métodos , Neoplasias Hepáticas/imunologia , Animais , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/microbiologia , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/microbiologia
12.
Ecotoxicol Environ Saf ; 221: 112464, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34198189

RESUMO

Antibiotics are widely used in the treatment of bacterial infections and as food additives in the livestock industry. The wide usage of antibiotics causes residues in animal products, like milk, eggs and meat. A number of studies have reported that antibiotic residues exist at high concentrations in watercourses around the world. Doxycycline (DH), oxytetracycline (OTCC) and florfenicol (FF) are the three most commonly used veterinary antibiotics in China. However, studies of the toxic effects of DH, OTCC and FF are limited. In this study, six-moth-old healthy male adult zebrafish were exposed to 0, 10, 30, 100 µg/L DH, OTCC or FF for 21 days. After exposure, some biochemical parameters changed significantly, including total cholesterol (TC), triglyceride (TG), pyruvate and acid phosphatase (ACP). In addition, mucus secretion in the gut decreased and the transcription of related genes also decreased significantly. Moreover, the composition of microbiota in the gut changed significantly. DH, OTCC and FF exposure caused the decrease of diversity of gut microbiota. The relative abundance of Proteobacteria increased significantly after OTCC and FF exposure and Fusobacteria decreased in all antibiotic-treated groups. Further functional prediction analysis also suggested changes in gut microbiota in the OTCC and FF-treated groups, especially those linked to metabolism. To support this idea, we confirmed that some glycolipid related genes also increased significantly in the liver of adult zebrafish after antibiotic exposure. According to these results, DH, OTCC or FF exposure could cause the gut microbiota dysbiosis and dysfunction, and hepatic metabolic disorder in adult male zebrafish.


Assuntos
Antibacterianos/toxicidade , Doxiciclina/toxicidade , Disbiose/induzido quimicamente , Microbioma Gastrointestinal/efeitos dos fármacos , Oxitetraciclina/toxicidade , Tianfenicol/análogos & derivados , Animais , Disbiose/metabolismo , Microbioma Gastrointestinal/genética , Glucose/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Tianfenicol/toxicidade , Peixe-Zebra/microbiologia
13.
Molecules ; 26(13)2021 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-34206736

RESUMO

Green tea can influence the gut microbiota by either stimulating the growth of specific species or by hindering the development of detrimental ones. At the same time, gut bacteria can metabolize green tea compounds and produce smaller bioactive molecules. Accordingly, green tea benefits could be due to beneficial bacteria or to microbial bioactive metabolites. Therefore, the gut microbiota is likely to act as middle man for, at least, some of the green tea benefits on health. Many health promoting effects of green tea seems to be related to the inter-relation between green tea and gut microbiota. Green tea has proven to be able to correct the microbial dysbiosis that appears during several conditions such as obesity or cancer. On the other hand, tea compounds influence the growth of bacterial species involved in inflammatory processes such as the release of LPS or the modulation of IL production; thus, influencing the development of different chronic diseases. There are many studies trying to link either green tea or green tea phenolic compounds to health benefits via gut microbiota. In this review, we tried to summarize the most recent research in the area.


Assuntos
Bactérias/efeitos dos fármacos , Microbioma Gastrointestinal/efeitos dos fármacos , Microbiota/efeitos dos fármacos , Fenóis/farmacologia , Extratos Vegetais/farmacologia , Chá , Animais , Antioxidantes/farmacologia , Catequina/farmacologia , Disbiose/complicações , Disbiose/tratamento farmacológico , Humanos , Inflamação/metabolismo , Neoplasias/complicações , Neoplasias/metabolismo , Obesidade/complicações , Obesidade/metabolismo , Fenóis/química , Fenóis/metabolismo , Polifenóis/farmacologia , Chá/química
14.
Molecules ; 26(14)2021 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-34299424

RESUMO

The gut epithelium is a mechanical barrier that protects the host from the luminal microenvironment and interacts with the gut microflora, which influences the development and progression of ulcerative colitis (UC). Licochalcone A (LA) exerts anti-inflammatory effects against UC; however, whether it also regulates both the gut barrier and microbiota during colitis is unknown. The current study was conducted to reveal the regulatory effects of LA on the intestinal epithelium and gut microflora in C57BL/6 mice subjected to dextran sodium sulfate (DSS). Sulfasalazine (SASP) was used as the positive control. Results of clinical symptoms evaluation, hematoxylin, and eosin (H&E) staining, and enzyme-linked immunosorbent (ELISA) assays showed that LA significantly inhibited DSS-induced weight loss, disease activity index (DAI) increase, histological damage, and gut inflammation. Additionally, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and immunohistochemical (IHC) analysis showed that LA maintained the integrity of the intestinal barrier by suppressing cell apoptosis and preserving the expression of tight junction (TJ) proteins. Notably, the optimal dose of LA for gut barrier preservation was low, while that for anti-inflammatory effects was high, indicating that LA might preserve gut barrier integrity via direct effects on the epithelial cells (ECs) and TJ proteins. Furthermore, 16S rRNA analysis suggested that the regulatory effect of LA on the gut microbiota differed distinctly according to dose. Correlation analysis indicated that a low dose of LA significantly modulated the intestinal barrier-associated bacteria as compared with a moderate or high dose of LA. Western blot (WB) analysis indicated that LA exhibited anti-UC activity partly by blocking the mitogen-activated protein kinase (MAPK) pathway. Our results further elucidate the pharmacological activity of LA against UC and will provide valuable information for future studies regarding on the regulatory effects of LA on enteric diseases.


Assuntos
Chalconas/farmacologia , Colite/tratamento farmacológico , Microbioma Gastrointestinal/efeitos dos fármacos , Animais , Chalconas/metabolismo , Colite/fisiopatologia , Colite Ulcerativa/induzido quimicamente , Colo/metabolismo , Sulfato de Dextrana/farmacologia , Modelos Animais de Doenças , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Sulfassalazina/farmacologia , Proteínas de Junções Íntimas/metabolismo
15.
Fish Shellfish Immunol ; 116: 52-60, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34216786

RESUMO

The aim of this study was to investigate the effects of dietary bile acids (BAs) on intestinal healthy status of tongue sole in terms of immunity, antioxidant status, digestive ability, mucosal barrier-related genes expression and microbiota. Three experimental diets were prepared with BA levels at 0 mg/kg (CT), 300 mg/kg (BA1) and 900 mg/kg (BA2) in a commercial basal diet. Each diet was fed to three replicates with 120 fish (10.87 ± 0.32 g) in each tank. After an 8-week feeding trial, growth parameters were significantly enhanced in both BAs supplementary groups (P < 0.05), and compared with CT group, survival rate in BA2 group was significantly improved (P < 0.05). Intestinal lysozyme activity and contents of immunoglobulin M and complement 3 were significantly increased in both BAs supplementary groups (P < 0.05), suggesting an enhancement effect on the non-specific immune response. BAs inclusion also significantly improved intestinal antioxidant capabilities by increasing antioxidase activities and decreasing malondialdehyde levels. In addition, compared with CT group, intestinal digestive ability was substantially enhanced as indicated by the significantly increased lipase activity in BA2 group (P < 0.05) and significantly increased amylase activity in BA1 and BA2 groups (P < 0.05). Coincidentally, BAs inclusion significantly upregulated the relative expression of intestinal mucosal barrier-related genes (P < 0.05). Further, dietary BAs distinctly remodeled intestinal microbiota by decreased the abundance of some potential pathogenic bacteria. In conclusion, dietary BAs supplementation is an effective way to improve the intestinal healthy status of tongue sole.


Assuntos
Ácidos e Sais Biliares/farmacologia , Suplementos Nutricionais , Linguados , Microbioma Gastrointestinal/efeitos dos fármacos , Mucosa Intestinal/efeitos dos fármacos , Fosfatase Alcalina/imunologia , Amilases/metabolismo , Animais , Complemento C3/imunologia , Dieta/veterinária , Proteínas de Peixes/metabolismo , Linguados/genética , Linguados/imunologia , Linguados/metabolismo , Linguados/microbiologia , Regulação da Expressão Gênica/efeitos dos fármacos , Imunoglobulina M/imunologia , Mucosa Intestinal/imunologia , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiologia , Lipase/metabolismo , Muramidase/imunologia , Oxirredutases/metabolismo , Peptídeo Hidrolases/metabolismo , Proteínas de Junções Íntimas/genética
16.
Nat Microbiol ; 6(8): 1043-1054, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34226711

RESUMO

Antimicrobial resistance poses a substantial threat to human health. The gut microbiome is considered a reservoir for potential spread of resistance genes from commensals to pathogens, termed the gut resistome. The impact of probiotics, commonly consumed by many in health or in conjunction with the administration of antibiotics, on the gut resistome is elusive. Reanalysis of gut metagenomes from healthy antibiotics-naïve humans supplemented with an 11-probiotic-strain preparation, allowing direct assessment of the gut resistome in situ along the gastrointestinal (GI) tract, demonstrated that probiotics reduce the number of antibiotic resistance genes exclusively in the gut of colonization-permissive individuals. In mice and in a separate cohort of humans, a course of antibiotics resulted in expansion of the lower GI tract resistome, which was mitigated by autologous faecal microbiome transplantation or during spontaneous recovery. In contrast, probiotics further exacerbated resistome expansion in the GI mucosa by supporting the bloom of strains carrying vancomycin resistance genes but not resistance genes encoded by the probiotic strains. Importantly, the aforementioned effects were not reflected in stool samples, highlighting the importance of direct sampling to analyse the effect of probiotics and antibiotics on the gut resistome. Analysing antibiotic resistance gene content in additional published clinical trials with probiotics further highlighted the importance of person-specific metagenomics-based profiling of the gut resistome using direct sampling. Collectively, these findings suggest opposing person-specific and antibiotic-dependent effects of probiotics on the resistome, whose contribution to the spread of antimicrobial resistance genes along the human GI tract merit further studies.


Assuntos
Antibacterianos/administração & dosagem , Bactérias/efeitos dos fármacos , Bactérias/genética , Proteínas de Bactérias/genética , Farmacorresistência Bacteriana , Microbioma Gastrointestinal/efeitos dos fármacos , Probióticos/administração & dosagem , Adulto , Bactérias/classificação , Bactérias/isolamento & purificação , Proteínas de Bactérias/metabolismo , Estudos de Coortes , Transplante de Microbiota Fecal , Fezes/microbiologia , Feminino , Trato Gastrointestinal/microbiologia , Humanos , Masculino , Metagenoma/efeitos dos fármacos , Pessoa de Meia-Idade , Adulto Jovem
17.
Am J Physiol Regul Integr Comp Physiol ; 321(3): R303-R316, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34259034

RESUMO

Neonatal antibiotics administered to human infants initiate gut microbiota dysbiosis that may have long-term effects on body weight and metabolism. We examined antibiotic-induced adaptations in pancreatic islets of the piglet, a well-accepted model of human infant microbiota and pancreas development. Neonatal piglets randomized to amoxicillin [30 mg/kg body wt/day; n = 7, antibiotic (ANTI)] or placebo [vehicle control; n = 7, control (CON)] from postnatal day (PND)0-13 were euthanized at PND7, 14, and 49. The metabolic phenotype along with functional, immunohistological, and transcriptional phenotypes of the pancreatic islets were studied. The gut microbiome was characterized by 16S rRNA gene sequencing, and microbial metabolites and microbiome-sensitive host molecules were measured. Compared with CON, ANTI PND7 piglets had elevated transcripts of genes involved in glucagon-like peptide 1 ((GLP-1) synthesis or signaling in islets (P < 0.05) coinciding with higher plasma GLP-1 (P = 0.11), along with increased tumor necrosis factor α (Tnf) (P < 0.05) and protegrin 1 (Npg1) (P < 0.05). Antibiotic-induced relative increases in Escherichia, Coprococcus, Ruminococcus, Dehalobacterium, and Oscillospira of the ileal microbiome at PND7 normalized after antibiotic withdrawal. In ANTI islets at PND14, the expression of key regulators pancreatic and duodenal homeobox 1 (Pdx1), insulin-like growth factor-2 (Igf2), and transcription factor 7-like 2 (Tcf7l2) was downregulated, preceding a 40% reduction of ß-cell area (P < 0.01) and islet insulin content at PND49 (P < 0.05). At PND49, a twofold elevated plasma insulin concentration (P = 0.07) was observed in ANTI compared with CON. We conclude that antibiotic treatment of neonatal piglets elicited gut microbial changes accompanied by phasic alterations in key regulatory genes in pancreatic islets at PND7 and 14. By PND49, reduced ß-cell area and islet insulin content were accompanied by elevated nonfasted insulin despite normoglycemia, indicative of islet stress.


Assuntos
Antibacterianos/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Células Secretoras de Insulina/efeitos dos fármacos , Animais , Microbioma Gastrointestinal/fisiologia , Glucagon/efeitos dos fármacos , Glucagon/metabolismo , Insulina/sangue , Células Secretoras de Insulina/metabolismo , Ilhotas Pancreáticas/efeitos dos fármacos , Ilhotas Pancreáticas/metabolismo , Suínos
18.
Molecules ; 26(14)2021 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-34299582

RESUMO

Olive vegetation water (OVW) is a by-product with a noticeable environmental impact; however, its polyphenols may be reused food and feed manufacture as high-value ingredients with antioxidant/antimicrobial activities. The effect of dietary supplementation with OVW polyphenols on the gut microbiota, carcass and breast quality, shelf life, and lipid oxidation in broiler chickens has been studied. Chicks were fed diets supplemented with crude phenolic concentrate (CPC) obtained from OVW (220 and 440 mg/kg phenols equivalent) until reaching commercial size. Cloacal microbial community (rRNA16S sequencing) was monitored during the growth period. Breasts were submitted to culture-dependent and -independent microbiological analyses during their shelf-life. Composition, fatty acid concentration, and lipid oxidation of raw and cooked thawed breasts were measured. Growth performance and gut microbiota were only slightly affected by the dietary treatments, while animal age influenced the cloacal microbiota. The supplementation was found to reduce the shelf life of breasts due to the growth of spoilers. Chemical composition and lipid oxidation were not affected. The hydroxytyrosol (HT) concentration varied from 178.6 to 292.4 ug/kg in breast muscle at the beginning of the shelf-life period. The identification of HT in meat demonstrates that the absorption and metabolism of these compounds was occurring efficiently in the chickens.


Assuntos
Galinhas , Conservação de Alimentos , Microbioma Gastrointestinal/efeitos dos fármacos , Carne , Olea/química , Polifenóis , Água , Animais , Galinhas/crescimento & desenvolvimento , Galinhas/microbiologia , Polifenóis/química , Polifenóis/farmacologia , Água/química , Água/farmacologia
19.
Front Immunol ; 12: 624434, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34305883

RESUMO

Host immunity plays a central role in the regulation of anti-tumour responses during checkpoint inhibitor therapy (CIT). The mechanisms involved in long lasting remission remain unclear. Animal studies have revealed that the microbiome influences the host immune response. This is supported by human studies linking a higher microbial richness and diversity with enhanced responses to CIT. This review focuses on the role of diet, the microbiome and the microbiome-derived metabolome in enhancing responses to current CIT in solid tissue cancers. The Western diet has been associated with dysbiosis, inflammation and numerous metabolic disorders. There is preliminary evidence that lifestyle factors including a high fibre diet are associated with improved responses to CIT via a potential effect on the microbiota. The mechanisms through which the microbiota may regulate long-term immunotherapy responses have yet to be determined, although bacterial-metabolites including short chain fatty acids (SCFAs) are recognized to have an impact on T cell differentiation, and may affect T effector/regulatory T cell balance. SCFAs were also shown to enhance the memory potential of activated CD8 T cells. Many therapeutic approaches including dietary manipulation and fecal transplantation are currently being explored in order to enhance immunotherapy responses. The microbiome-derived metabolome may be one means through which bacterial metabolic products can be monitored from the start of treatment and could be used to identify patients at risk of poor immunotherapy responses. The current review will discuss recent advances and bring together literature from related fields in nutrition, oncology and immunology to discuss possible means of modulating immunity to improve responses to current CIT.


Assuntos
Dieta/métodos , Microbioma Gastrointestinal/efeitos dos fármacos , Inibidores de Checkpoint Imunológico/uso terapêutico , Metaboloma/imunologia , Neoplasias/tratamento farmacológico , Animais , Bactérias/metabolismo , Dieta/efeitos adversos , Disbiose/complicações , Microbioma Gastrointestinal/imunologia , Humanos , Imunomodulação , Estilo de Vida , Metaboloma/efeitos dos fármacos , Camundongos , Neoplasias/imunologia
20.
Int J Biol Macromol ; 185: 582-591, 2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34216660

RESUMO

The effects of a novel Flammulina velutipes polysaccharide (FVP) on intestinal microbiota, immune repertoire and heart transcriptome were investigated in this study. The results showed that FVP treatment could effectively regulate the abundance of colonic microbiota. And FVP exhibited obvious immunoregulatory effect by influencing V gene and J gene fragments usage on TCRα chain. The usage frequency of TRBV1, TRBJ1-6 and TRBJ1-5 were significantly altered, and 41 V-J pairs were identified with obvious difference after FVP treatment. Furthermore, the mRNA of mice heart was analyzed by transcriptome assay. Total 525 genes and 1587 mRNA were significantly changed after FVP treatment. KEGG annotation indicated that the up-regulated mRNA was enriched in 17 pathways including adherens junction, mTOR signaling pathway, insulin signaling pathway, mitophagy, tight junction, PPAR signaling pathway and TNF signaling pathway, etc. Meanwhile, the down-regulated mRNA was gathered in AMPK signaling pathway, metabolism of xenobiotics by cytochrome P450, apelin signaling pathway, PPAR signaling pathway, PI3K-Akt signaling pathway, insulin signaling pathway, cardiac muscle contraction, adrenergic signaling in cardiomyocytes, Fc gamma R-mediated phagocytosis, etc. The great potential exhibited by FVP could make it an ideal candidate as complementary medicine or functional food for promotion of health.


Assuntos
Bactérias/isolamento & purificação , Flammulina/química , Perfilação da Expressão Gênica/métodos , Miocárdio/química , Polissacarídeos/administração & dosagem , Receptores de Antígenos de Linfócitos T alfa-beta/genética , Animais , Bactérias/efeitos dos fármacos , Bactérias/genética , Microbioma Gastrointestinal/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Coração/efeitos dos fármacos , Masculino , Camundongos , Anotação de Sequência Molecular , Filogenia , Polissacarídeos/farmacologia , RNA Bacteriano/genética , RNA Ribossômico 16S/genética , Análise de Sequência de RNA , Xenobióticos
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