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1.
World J Gastroenterol ; 25(40): 6129-6144, 2019 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-31686768

RESUMO

BACKGROUND: Constipation is a common functional gastrointestinal disorder and its etiology is multifactorial. Growing evidence suggests that intestinal dysbiosis is associated with the development of constipation. Prebiotics are subjected to bacterial fermentation in the gut to produce short-chain fatty acids (SCFAs), which can help relieve constipation symptoms. The prebiotic UG1601 consists of inulin, lactitol, and aloe vera gel, which are known laxatives, but randomized, controlled clinical trials that examine the effects of this supplement on gut microbiota composition are lacking. AIM: To assess the efficacy of the prebiotic UG1601 in suppressing constipation-related adverse events in subjects with mild constipation. METHODS: Adults with a stool frequency of less than thrice a week were randomized to receive either prebiotics or a placebo supplement for 4 wk. All participants provided their fecal and blood samples at baseline and at the end of intervention. Gastrointestinal symptoms and stool frequency were evaluated. The concentrations of serum endotoxemia markers and fecal SCFAs were determined. The relative abundance of SCFA-producing bacteria and the gut microbial community in the responders and non-responders in the prebiotics supplementation group were evaluated. RESULTS: There were no significant differences in gastrointestinal symptoms between groups, although the prebiotic group showed greater symptom improvement. However, after prebiotic usage, serum cluster of differentiation (CD) 14 and lipopolysaccharide (LPS) concentrations were significantly decreased (CD14, P = 0.012; LPS, P < 0.001). The change in LPS concentration was significantly larger in the prebiotic group than in the placebo group (P < 0.001). Fecal SCFAs concentrations did not differ between groups, while the relative abundance of Roseburia hominis, a major butyrate producer, was significantly increased in the prebiotic group (P = 0.045). The abundances of the phylum Firmicutes and the family Lachnospiraceae (phylum Firmicutes, class Clostridia) (P = 0.009) were decreased in the responders within the prebiotic group. In addition, the proportions of the phylum Firmicutes, the class Clostridia, and the order Clostridiales were inversely correlated with several fecal SCFAs (P < 0.05). CONCLUSION: Alterations in gut microbiota composition, including a decrease in the phylum Firmicutes and an increase in butyrate-producing bacteria, following prebiotic UG1601 supplementation might help alleviate symptom scores and endotoxemia.


Assuntos
Constipação Intestinal/dietoterapia , Disbiose/dietoterapia , Endotoxemia/dietoterapia , Microbioma Gastrointestinal/efeitos dos fármacos , Prebióticos/administração & dosagem , Adulto , Clostridiales/efeitos dos fármacos , Clostridiales/isolamento & purificação , Constipação Intestinal/complicações , Constipação Intestinal/diagnóstico , Método Duplo-Cego , Disbiose/diagnóstico , Disbiose/microbiologia , Endotoxemia/diagnóstico , Endotoxemia/microbiologia , Ácidos Graxos Voláteis/análise , Fezes/química , Fezes/microbiologia , Feminino , Humanos , Inulina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Placebos/administração & dosagem , Preparações de Plantas/administração & dosagem , Índice de Gravidade de Doença , Álcoois Açúcares/administração & dosagem , Resultado do Tratamento , Adulto Jovem
2.
Int J Mol Sci ; 20(19)2019 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-31581682

RESUMO

Recently, bioactive peptides have attracted attention for their therapeutic applications in the pharmaceutical industry. Among them, antimicrobial peptides are candidates for new antibiotic drugs. Since pseudin-2 (Ps), isolated from the skin of the paradoxical frog Pseudis paradoxa, shows broad-spectrum antibacterial activity with high cytotoxicity, we previously designed Ps-K18 with a Lys substitution for Leu18 in Ps, which showed high antibacterial activity and low toxicity. Here, we examined the potency of Ps-K18, aiming to develop antibiotics derived from bioactive peptides for the treatment of Gram-negative sepsis. We first investigated the antibacterial mechanism of Ps-K18 based on confocal micrographs and field emission scanning electron microscopy, confirming that Ps-K18 targets the bacterial membrane. Anti-inflammatory mechanism of Ps-K18 was investigated by secreted alkaline phosphatase reporter gene assays and RT-PCR, which revealed that Ps-K18 activates innate defense via Toll-like receptor 4-mediated nuclear factor-kappa B signaling pathways. Moreover, we investigated the antiseptic effect of Ps-K18 using a lipopolysaccharide or Escherichia coli K1-induced septic shock mouse model. Ps-K18 significantly reduced bacterial growth and inflammatory responses in the septic shock model. Ps-K18 showed low renal and liver toxicity and attenuated lung damage effectively. This study suggests that Ps-K18 is a potent peptide antibiotic that could be applied therapeutically to Gram-negative sepsis.


Assuntos
Proteínas de Anfíbios/química , Anti-Infecciosos Locais/farmacologia , Anti-Inflamatórios/farmacologia , Peptídeos Catiônicos Antimicrobianos/farmacologia , Animais , Peptídeos Catiônicos Antimicrobianos/química , Sobrevivência Celular/efeitos dos fármacos , Modelos Animais de Doenças , Endotoxemia/tratamento farmacológico , Endotoxemia/microbiologia , Escherichia coli/efeitos dos fármacos , Escherichia coli/ultraestrutura , Humanos , Macrófagos , Camundongos , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo
3.
Indian J Med Res ; 149(6): 763-770, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31496529

RESUMO

Background & objectives: In acute pancreatitis (AP) gut barrier dysfunction is considered as an important predisposing factor leading to increased intestinal permeability (IP). In this study a pooled analysis of data published in our previous four studies on various aspects of gut permeability and endotoxaemia in patients with AP was attempted to find an association between increased IP and severity of disease and associated complications. Methods: This study was a pooled analysis of data of four previously published prospective studies on AP. Gut permeability, assessed by lactulose/mannitol excretion in urine and endotoxin core antibodies type IgG and IgM (EndoCab IgG and IgM) were measured on days zero and seven (D0 and D7) of admission. All patients received standard treatment of AP. We studied whether IgG and IgM anti-endotoxin titres and lactulose-mannitol ratio (LMR) at admission and D7 were associated with organ failure, infection and mortality. Results: The titres of anti-endotoxin IgG and IgM were lower in all patients of AP (n=204), both in mild AP (n=24) and severe AP (n=180) in the first week, compared to controls (n=15). There was no significant difference in serum IgG and IgM anti-endotoxin levels and LMR at baseline and at D7 among patients with organ failure, infection and mortality. Interpretation & conclusions: Our findings showed that serum IgG and IgM anti-endotoxin titres and LMR at admission and at day 7 were not associated with organ failure, infection, and death of patients with AP.


Assuntos
Endotoxemia/imunologia , Endotoxinas/imunologia , Pancreatite/imunologia , Permeabilidade , Adulto , Anticorpos/imunologia , Proteína C-Reativa/imunologia , Endotoxemia/metabolismo , Endotoxemia/microbiologia , Endotoxemia/patologia , Endotoxinas/urina , Feminino , Humanos , Imunoglobulina G/imunologia , Imunoglobulina M/imunologia , Mucosa Intestinal/imunologia , Mucosa Intestinal/microbiologia , Mucosa Intestinal/patologia , Intestinos/microbiologia , Intestinos/patologia , Lactulose/urina , Masculino , Manitol/urina , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/imunologia , Insuficiência de Múltiplos Órgãos/metabolismo , Insuficiência de Múltiplos Órgãos/microbiologia , Insuficiência de Múltiplos Órgãos/patologia , Pancreatite/microbiologia
4.
Nutrients ; 11(8)2019 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-31412673

RESUMO

(1) Background: Nutrition is a major lifestyle factor that can prevent the risk of cognitive impairment and dementia. Diet-induced metabolic endotoxemia has been proposed as a major root cause of inflammation and these pathways emerge as detrimental factors of healthy ageing. The aim of this paper was to update research focusing on the relationship between a fat-rich diet and endotoxemia, and to discuss the potential role of endotoxemia in cognitive performances. (2) Methods: We conducted a non-systematic literature review based on the PubMed database related to fat-rich meals, metabolic endotoxemia and cognitive disorders including dementia in humans. A total of 40 articles out of 942 in the first screening met the inclusion criteria. (3) Results: Evidence suggested that a fat-rich diet, depending on its quality, quantity and concomitant healthy food components, could influence metabolic endotoxemia. Since only heterogeneous cross-sectional studies are available, it remains unclear to what extent endotoxemia could be associated or not with cognitive disorders and dementia. (4) Conclusions: A fat-rich diet has the capability to provide significant increases in circulating endotoxins, which highlights nutritional strategies as a promising area for future research on inflammatory-associated diseases. The role of endotoxemia in cognitive disorders and dementia remains unclear and deserves further investigation.


Assuntos
Bactérias/metabolismo , Envelhecimento Cognitivo/psicologia , Disfunção Cognitiva/etiologia , Gorduras na Dieta/efeitos adversos , Endotoxemia/etiologia , Microbioma Gastrointestinal , Adulto , Fatores Etários , Idoso , Cognição , Disfunção Cognitiva/sangue , Disfunção Cognitiva/microbiologia , Disfunção Cognitiva/psicologia , Endotoxemia/sangue , Endotoxemia/microbiologia , Endotoxemia/psicologia , Feminino , Interações Hospedeiro-Patógeno , Humanos , Masculino , Pessoa de Meia-Idade , Valor Nutritivo , Prognóstico , Medição de Risco , Fatores de Risco , Adulto Jovem
5.
Food Funct ; 10(6): 3368-3378, 2019 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-31099356

RESUMO

Gut microbiota has been identified as an important factor in the link between nutrient excess and obesity. The aim of this study was to confirm whether bovine α-lactalbumin hydrolysates (LAH) can ameliorate high-fat diet (HFD)-induced endotoxemia and systematic inflammation by modulating the structure of gut microbiota in mice. The results showed that LAH changed the overall structure of gut microbiota in HFD-induced obese mice. LAH increased the Bacteroidetes/Firmicutes ratios and the relative abundance of S24-7, Lachnospiraceae and Blautia. Spearman's correlation analysis revealed significant correlations between the alteration of gut microbiota and obesity-related indexes. LAH decreased the HFD-induced protein expression of G protein-coupled receptor 43 (GPR43) and 41 (GPR41) in the colon tissue. Besides, LAH inhibited the destruction of the gut barrier through the up-regulation of tight junction protein (zonulin/zonula occludens (ZO)-1 and occludin) expression and the decrease of toll-like receptor 4 (TLR4) protein expression in the colon tissue. LAH also significantly reduced the concentration of tumour cell necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in both serum and colon and decreased the level of lipopolysaccharides (LPS) in serum and feces, leading to reduced systematic inflammation and metabolic endotoxemia. In summary, LAH partly modulated the gut microbial composition and structure, and alleviated the obesity-associated inflammation. These findings shed light on bovine α-lactalbumin hydrolysate as a potential functional food ingredient to prevent obesity-related inflammation.


Assuntos
Endotoxemia/dietoterapia , Microbioma Gastrointestinal , Lactalbumina/química , Obesidade/dietoterapia , Hidrolisados de Proteína/metabolismo , Animais , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Bactérias/metabolismo , Bovinos , Dieta Hiperlipídica/efeitos adversos , Endotoxemia/etiologia , Endotoxemia/imunologia , Endotoxemia/microbiologia , Humanos , Lactalbumina/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/etiologia , Obesidade/imunologia , Obesidade/microbiologia , Hidrolisados de Proteína/química , Receptores Acoplados a Proteínas-G/genética , Receptores Acoplados a Proteínas-G/imunologia , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia
6.
Nat Immunol ; 20(2): 129-140, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30664762

RESUMO

Basophils are evolutionarily conserved in vertebrates, despite their small numbers and short life span, suggesting that they have beneficial roles in maintaining health. However, these roles are not fully defined. Here we demonstrate that basophil-deficient mice exhibit reduced bacterial clearance and increased morbidity and mortality in the cecal ligation and puncture (CLP) model of sepsis. Among the several proinflammatory mediators that we measured, tumor necrosis factor (TNF) was the only cytokine that was significantly reduced in basophil-deficient mice after CLP. In accordance with that observation, we found that mice with genetic ablation of Tnf in basophils exhibited reduced systemic concentrations of TNF during endotoxemia. Moreover, after CLP, mice whose basophils could not produce TNF, exhibited reduced neutrophil and macrophage TNF production and effector functions, reduced bacterial clearance, and increased mortality. Taken together, our results show that basophils can enhance the innate immune response to bacterial infection and help prevent sepsis.


Assuntos
Basófilos/imunologia , Endotoxemia/imunologia , Imunidade Inata , Fator de Necrose Tumoral alfa/imunologia , Transferência Adotiva , Animais , Basófilos/metabolismo , Ceco/microbiologia , Modelos Animais de Doenças , Endotoxemia/microbiologia , Endotoxemia/terapia , Microbioma Gastrointestinal , Humanos , Lipopolissacarídeos/imunologia , Macrófagos/imunologia , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Neutrófilos/imunologia , Neutrófilos/metabolismo , Taxa de Sobrevida , Fator de Necrose Tumoral alfa/genética
7.
Medicine (Baltimore) ; 97(46): e12685, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30431563

RESUMO

BACKGROUND: Both selective digestive decontamination (SDD) and probiotics have been reported to reduce endotoxemia. However, the available results are conflicting and few studies have investigated the combined effect of SDD and probiotics. This study aimed to examine the effectiveness of a comprehensive preoperative regimen of SDD in combination with probiotics and smectite on perioperative endotoxemia and cytokine activation in patients who underwent elective cardiac surgery with cardiopulmonary bypass (CPB) in a pilot, prospective, randomized, controlled trial. METHODS: Patients who underwent elective Aortic Valve Replacement or Mitral Valve Replacement surgery from July 2010 to March 2015 were included. In total, 30 eligible patients were randomly assigned to receive either the comprehensive preoperative regimen (n = 15) (a combination of preoperative SDD, probiotics, and smectite) or the control group (n = 15) who did not receive this treatment. The levels of endotoxin, IL-6, and procalcitonin were measured at the time before anesthesia induction, immediately after cardiopulmonary bypass (CPB), 24 hours after CPB, and 48 hours after CPB. The primary outcomes were changes in endotoxin, IL-6, and procalcitonin concentrations after CPB. RESULTS: The mean levels of change in endotoxin levels after CPB in patients receiving the comprehensive preoperative regimen was marginally significantly lower than those in control group (F = 4.0, P = .0552) but was not significantly different for procalcitonin (F = .14, P = .7134). An interaction between group and time for IL-6 was identified (F = 4.35, P = .0231). The increase in IL-6 concentration immediately after CPB in the comprehensive preoperative group was significantly lower than that in the control group (P = .0112). The changes in IL-6 concentration at 24 hours and 48 hours after CPB were not significant between the comprehensive preoperative group and control group. CONCLUSION: The present pilot, prospective, randomized, controlled study in patients undergoing cardiac surgery with CPB demonstrated that 3 days of a comprehensive preoperative regime of SDD in combination with probiotics and smectite may reduce the endotoxin and IL-6 levels after CPB compared with the control group.


Assuntos
Ponte Cardiopulmonar/efeitos adversos , Descontaminação/métodos , Sistema Digestório/microbiologia , Endotoxemia/prevenção & controle , Complicações Pós-Operatórias/prevenção & controle , Probióticos/uso terapêutico , Silicatos/uso terapêutico , Adulto , Citocinas/metabolismo , Endotoxemia/etiologia , Endotoxemia/microbiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/microbiologia , Cuidados Pré-Operatórios/métodos , Estudos Prospectivos
8.
Autoimmunity ; 51(6): 304-309, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30417696

RESUMO

Anti-citrullinated protein autoantibodies (ACPA) precede the onset of clinical and subclinical rheumatoid arthritis (RA). ACPA are frequently generated in further chronic inflammatory diseases, e.g. chronic obstructive pulmonary disease, lupus, periodontitis (PD), characterized by citrullination and mucosal as well as systemic autoimmunity against citrullinated proteins. PD is of particular interest, as it exhibits two sources of citrullination, namely peptidylarginine deiminase 4 (PAD4) of periodontal neutrophils and neutrophil extracellular traps (NETs) as well as the PAD of Porphyromonas gingivalis (PPAD). Whereas the PAD4-citrullinated host peptides and/or proteins occur physiologically, PPAD-citrullinated ones appear under pathological conditions as neo-antigens. Frequently, the oral pathogens P. gingivalis and A. actinomycetemcomitans directly and indirectly participate in synovitis in RA, providing topical citrullination: P. gingivalis via PPAD and A. actinomycetemcomitans via leukotoxin A-mediated ROS-independent NET formation. In addition, transient bacteraemia due to tooth brushing indicates the possibility that citrullinated peptides and/or proteins from periodontium regularly enter the blood circulation. In this way, the mucosal firewall is evaded and the systemic immune response against citrullinated peptides and/or proteins is facilitated. However, the role of swallowed PD-derived sludge for the induction of oral tolerance remains to be established. We hypothesize (I) PD-driven endotoxemia may increase the host responsiveness to autoantigens via TLR4 activation and (II) this participates in development and propagation of RA (III) circulating PD-derived bacterial DNA is taken up by phagocytes, activates TLR9, and thus increases the responsiveness to autoantigens.


Assuntos
Anticorpos Anti-Proteína Citrulinada/imunologia , Artrite Reumatoide/imunologia , Autoantígenos/imunologia , Endotoxemia/imunologia , Periodontite/imunologia , Desiminases de Arginina em Proteínas/metabolismo , Aggregatibacter actinomycetemcomitans/enzimologia , Aggregatibacter actinomycetemcomitans/genética , Artrite Reumatoide/microbiologia , Autoantígenos/metabolismo , Proteínas de Bactérias/imunologia , Proteínas de Bactérias/metabolismo , Citrulinação/imunologia , Citrulina/metabolismo , DNA Bacteriano/imunologia , DNA Bacteriano/metabolismo , Endotoxemia/microbiologia , Armadilhas Extracelulares/enzimologia , Armadilhas Extracelulares/imunologia , Proteínas Hemolisinas/imunologia , Proteínas Hemolisinas/metabolismo , Humanos , Neutrófilos/enzimologia , Neutrófilos/imunologia , Periodontite/microbiologia , Periodonto/citologia , Periodonto/imunologia , Periodonto/metabolismo , Periodonto/microbiologia , Porphyromonas gingivalis/enzimologia , Porphyromonas gingivalis/genética , Desiminases de Arginina em Proteínas/imunologia , Receptor 4 Toll-Like/imunologia , Receptor 4 Toll-Like/metabolismo , Receptor Toll-Like 9/imunologia , Receptor Toll-Like 9/metabolismo
9.
Alcohol Clin Exp Res ; 42(12): 2313-2325, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30320890

RESUMO

BACKGROUND: There is strong evidence that alcoholism leads to dysbiosis in both humans and animals. However, it is unclear how changes in the intestinal microbiota (IM) relate to ethanol (EtOH)-induced disruption of gut-liver homeostasis. We investigated this issue using selectively bred Sardinian alcohol-preferring (sP) rats, a validated animal model of excessive EtOH consumption. METHODS: Independent groups of male adult sP rats were exposed to the standard, home-cage 2-bottle "EtOH (10% v/v) versus water" choice regimen with unlimited access for 24 h/d (Group Et) for 3 (T1), 6 (T2), and 12 (T3) consecutive months. Control groups (Group Ct) were composed of matched-age EtOH-naïve sP rats. We obtained samples from each rat at the end of each experimental time, and we used blood and colon tissues for intestinal barrier integrity and/or liver pathology assessments and used stool samples for IM analysis with 16S ribosomal RNA gene sequencing. RESULTS: Rats in Group Et developed hepatic steatosis and elevated serum transaminases and endotoxin/lipopolysaccharide (LPS) levels but no other liver pathological changes (i.e., necrosis/inflammation) or systemic inflammation. While we did not find any apparent alteration of the intestinal colonic mucosa, we found that rats in Group Et exhibited significant changes in IM composition compared to the rats in Group Ct. These changes were sustained throughout T1, T2, and T3. In particular, Ruminococcus, Coprococcus, and Streptococcus were the differentially abundant microbial genera at T3. The KEGG Ortholog profile revealed that IM functional modules, such as biosynthesis, transport, and export of LPS, were also enriched in Group Et rats at T3. CONCLUSIONS: We showed that chronic, voluntary EtOH consumption induced liver injury and endotoxemia together with dysbiotic changes in sP rats. This work sets the stage for improving our knowledge of the prevention and treatment of EtOH-related diseases.


Assuntos
Consumo de Bebidas Alcoólicas/psicologia , Endotoxemia/microbiologia , Microbioma Gastrointestinal/efeitos dos fármacos , Hepatopatias Alcoólicas/microbiologia , Consumo de Bebidas Alcoólicas/genética , Animais , Colo/microbiologia , Fígado Gorduroso Alcoólico/microbiologia , Fígado Gorduroso Alcoólico/patologia , Intestinos/patologia , Lipopolissacarídeos/sangue , Fígado/patologia , Testes de Função Hepática , Masculino , RNA Ribossômico 16S , Ratos , Transaminases/sangue
10.
Sci Rep ; 8(1): 13632, 2018 09 11.
Artigo em Inglês | MEDLINE | ID: mdl-30206252

RESUMO

Neurologic melioidosis occurs in both human and animals; however, the mechanism by which the pathogen Burkholderia pseudomallei invades the central nervous system (CNS) remains unclear. B. pseudomallei-loaded Ly6C cells have been suggested as a putative portal; however, during melioidosis, lipopolysaccharide (LPS) can drive disruption of the blood-brain barrier (BBB). This study aims to test whether the Trojan horse-like mechanism occurs during endotoxemia. The expression levels of cerebral cytokines, chemokines and cell adhesion molecules; the activation of astrocytes, microglia and endothelial cells; and the increased vascular permeability and brain-infiltrating leukocytes were evaluated using B. pseudomallei, B. thailandensis, B. cenocepacia and B. multivorans LPS-induced brains. Accordingly, different degrees of BBB damage in those brains with endotoxemia were established. The B. multivorans LPS-induced brain exhibited the highest levels of disruptive BBB according to the above mediators/indicators. Into these distinct groups of endotoxemic mice, B. pseudomallei-loaded Ly6C cells or free B. pseudomallei were adoptively transferred at equal bacterial concentrations (103 CFU). The bacterial load and number of cases of meningeal neutrophil infiltration in the brains of animals treated with B. pseudomallei-loaded Ly6C cells were higher than those in brains induced by free B. pseudomallei in any of the endotoxemic groups. In particular, these results were reproducible in B. multivorans LPS-induced brains. We suggest that B. pseudomallei-loaded cells can act as a Trojan horse and are more effective than free B. pseudomallei in invading the CNS under septic or endotoxemic conditions even when there is a high degree of BBB disruption.


Assuntos
Encéfalo/microbiologia , Burkholderia pseudomallei/metabolismo , Encefalite/microbiologia , Endotoxemia/microbiologia , Lipopolissacarídeos/metabolismo , Animais , Astrócitos/microbiologia , Astrócitos/patologia , Barreira Hematoencefálica/metabolismo , Barreira Hematoencefálica/microbiologia , Barreira Hematoencefálica/patologia , Encéfalo/patologia , Burkholderia pseudomallei/patogenicidade , Permeabilidade Capilar/genética , Moléculas de Adesão Celular/metabolismo , Sistema Nervoso Central/metabolismo , Sistema Nervoso Central/microbiologia , Sistema Nervoso Central/patologia , Quimiocinas/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Encefalite/metabolismo , Encefalite/patologia , Células Endoteliais/metabolismo , Células Endoteliais/microbiologia , Células Endoteliais/patologia , Endotoxemia/metabolismo , Endotoxemia/patologia , Humanos , Camundongos , Microglia/metabolismo , Microglia/patologia
11.
Infection ; 46(6): 793-799, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30066228

RESUMO

PURPOSE: Endotoxin is a component of the outer membrane of gram-negative bacteria that live in the intestine. Endotoxinemia is reported in non-alcoholic fatty liver disease and in cirrhotic patients, causing various biological and clinical effects in the host. It is not known whether endotoxinemia occurs in chronic hepatitis C patients (CHC), therefore we evaluated the occurrence of endotoxinemia and its effect on inflammation, liver damage, insulin resistance (IR) and atherosclerosis. METHODS: Consecutive CHC patients assessed by liver biopsy were enrolled. Endotoxinemia was evaluated by LAL test. IR was estimated by HOMA-IR. Serum TNF-α, IL-8, adiponectin and MCP-1 were measured with ELISA tests. Oxidative stress was estimated by circulating IgG against malondialdehyde adducts with human serum albumin (MDA-HAS). Carotid atherosclerosis was assessed by ultrasonography. RESULTS: Endotoxinemia was found in 60% of the 126 patients enrolled. A serum level-dependent association between endotoxinemia, steatosis (p < 0.001) and HOMA-IR (p < 0.006) was observed. Patients with endotoxinemia showed significant increase in TNF-α and IL8 levels. TNF-α correlated with steatosis (p <  0.001) and HOMA-IR (p < 0.03), whereas IL8 correlated with steatosis (p =  <0.001), TNF-α (p < 0.04) and atherosclerosis (p < 0.01). The highest levels of endotoxinemia were associated with oxidative stress and a higher prevalence of carotid atherosclerosis. Multivariate logistic regression analysis showed that the independent factors associated with endotoxinemia were hepatic steatosis, HOMA-IR, IL8 and MDA-HAS. CONCLUSIONS: Endotoxinemia occurs with high frequency in CHC patients and contributes to the development of hepatic steatosis, IR and atherosclerosis through increased pro-inflammatory cytokines and oxidative stress. Anti-endotoxin treatment could be of clinical relevance.


Assuntos
Aterosclerose/microbiologia , Endotoxemia/epidemiologia , Fibrose/microbiologia , Hepatite C Crônica/complicações , Inflamação/microbiologia , Resistência à Insulina , Estresse Oxidativo , Adolescente , Adulto , Idoso , Quimiocinas/metabolismo , Citocinas/metabolismo , Endotoxemia/complicações , Endotoxemia/microbiologia , Fígado Gorduroso/microbiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Adulto Jovem
12.
Metab Syndr Relat Disord ; 16(7): 321-328, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29957105

RESUMO

Diet with increased intake of energy-rich foods has long been implicated in the etiology of metabolic syndrome. In recent years, an increasing body of evidence has emerged that suggests that the intestinal microbial flora or "gut microbiota" may play a crucial role in the development of metabolic syndrome and associated disorders. Studies on animals and humans have shown that diet-induced changes in gut microbiota may be causally involved in the pathogenesis of metabolic syndrome. This article reviews the available evidence from studies on animal models and humans with or without metabolic syndrome that have investigated the impact of diet on intestinal microbial composition and activity on the metabolic syndrome. The underlying mechanisms or pathways that link diet and altered gut microbiota to the development of metabolic syndrome are discussed with special emphasis on gut microbiota-induced changes in intestinal short-chain fatty acids, metabolic endotoxemia, low-grade systemic inflammation, and innate immune system activation and their inter-relationships to metabolic syndrome.


Assuntos
Dieta/efeitos adversos , Disbiose/etiologia , Síndrome Metabólica/complicações , Experimentação Animal , Animais , Ensaios Clínicos como Assunto , Dieta Hiperlipídica , Endotoxemia/complicações , Endotoxemia/microbiologia , Microbioma Gastrointestinal/fisiologia , Humanos , Inflamação/complicações , Inflamação/microbiologia , Síndrome Metabólica/microbiologia
13.
Mol Nutr Food Res ; 62(11): e1800160, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29665619

RESUMO

SCOPE: Gut microbiota dysbiosis, intestinal barrier failure, obesity, metabolic endotoxemia, and pro-inflammatory status promote cardiovascular risk. However, the modulation of the gut microbiome to prevent endotoxemia in obesity has been scarcely studied. We investigated the association between gut microbiota modulation and plasma lipopolysaccharide-binding protein (LBP), a surrogate marker of endotoxemia, in overweight-obese individuals. METHODS AND RESULTS: In a randomized trial, 49 overweight-obese subjects (body mass index> 27 kg m-2 ) with mild hypelipidemia daily consumed, in a cross-over fashion, two doses (D1 and D2, lasting 3 weeks each) of pomegranate extract (PE) or placebo alternating with 3 weeks of wash-out periods. A significant decrease (p < 0.05) of plasma LBP and a marginal decrease (p = 0.054) of high-sensitivity C-reactive protein were observed, but only after PE-D2 administration (656 mg phenolics). 16S rDNA sequencing analyses revealed the increase of microorganisms important for maintaining normal balance of gut microbiota and gut barrier function, particularly Bacteroides, Faecalibacterium, Butyricicoccus, Odoribacter, and Butyricimonas. PE-D2 also decreased pro-inflammatory microorganisms including Parvimonas, Methanobrevibacter, and Methanosphaera. Remarkably, plasma LBP reduction was significantly associated (p < 0.05) with both Faecalibacterium and Odoribacter increase and Parvimonas decrease. CONCLUSIONS: Consumption of PE decreased endotoxemia in overweight-obese individuals by reshaping the gut microbiota, mainly through the modulation of Faecalibacterium, Odoribacter, and Parvimonas.


Assuntos
Proteínas de Transporte/sangue , Microbioma Gastrointestinal/efeitos dos fármacos , Lythraceae/química , Glicoproteínas de Membrana/sangue , Sobrepeso/dietoterapia , Extratos Vegetais/farmacologia , Proteínas da Fase Aguda , Adulto , Proteína C-Reativa/análise , DNA Ribossômico , Suplementos Nutricionais , Endotoxemia/dietoterapia , Endotoxemia/metabolismo , Endotoxemia/microbiologia , Feminino , Microbioma Gastrointestinal/genética , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/dietoterapia , Obesidade/microbiologia , Sobrepeso/microbiologia
14.
Nutrition ; 54: 40-47, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29705500

RESUMO

OBJECTIVES: The beneficial effects of pro-, pre-, and synbiotics on obesity with insulin resistance have been reported previously. However, the strain-specific effect of probiotics and the combination with various types of prebiotic fiber yield controversial outcomes and limit clinical applications. Our previous study demonstrated that the probiotic Lactobacillus paracasei (L. paracasei) HII01, prebiotic xylooligosaccharide (XOS), and synbiotics share similar efficacy in attenuating cardiac mitochondrial dysfunction in obese-insulin resistant rats. Nonetheless, the roles of HII01 and XOS on gut dysbiosis and gut inflammation under obese-insulin resistant conditions have not yet, to our knowledge, been investigated. Our hypothesis was that pro-, pre-, and synbiotics improve the metabolic parameters in obese-insulin resistant rats by reducing gut dysbiosis and gut inflammation. METHODS: Male Wistar rats were fed with either a normal or high-fat diet that contained 19.77% and 59.28% energy from fat, respectively, for 12 wk. Then, the high-fat diet rats were fed daily with a 108 colony forming unit of the probiotic HII01, 10% prebiotic XOS, and synbiotics for 12 wk. The metabolic parameters, serum lipopolysaccharide levels, fecal Firmicutes/Bacteroidetes ratios, levels of Enterobacteriaceae, Bifidobacteria, and gut proinflammatory cytokine gene expression were quantified. RESULTS: The consumption of probiotic L. paracasei HII01, prebiotic XOS, and synbiotics for 12 wk led to a decrease in metabolic endotoxemia, gut dysbiosis (a reduction in the Firmicutes/Bacteroidetes ratio and Enterobacteriaceae), and gut inflammation in obese-insulin resistant rats. CONCLUSIONS: Pro-, pre-, and synbiotics reduced gut dysbiosis and gut inflammation, which lead to improvements in metabolic dysfunction in obese-insulin resistant rats.


Assuntos
Suplementos Nutricionais , Glucuronatos/administração & dosagem , Lactobacillus paracasei , Obesidade/microbiologia , Oligossacarídeos/administração & dosagem , Simbióticos/administração & dosagem , Animais , Bifidobacterium/isolamento & purificação , Dieta Hiperlipídica , Disbiose/microbiologia , Endotoxemia/microbiologia , Microbioma Gastrointestinal , Resistência à Insulina , Masculino , Prebióticos/administração & dosagem , Probióticos/administração & dosagem , Ratos , Ratos Wistar
15.
Liver Transpl ; 24(6): 752-761, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29500907

RESUMO

Liver transplantation (LT) improves daily function and ameliorates gut microbial composition. However, the effect of LT on microbial functionality, which can be related to overall patient benefit, is unclear and could affect the post-LT course. The aims were to determine the effect of LT on gut microbial functionality focusing on endotoxemia, bile acid (BA), ammonia metabolism, and lipidomics. We enrolled outpatient patients with cirrhosis on the LT list and followed them until 6 months after LT. Microbiota composition (Shannon diversity and individual taxa) and function analysis (serum endotoxin, urinary metabolomics and serum lipidomics, and stool BA profile) and cognitive tests were performed at both visits. We enrolled 40 patients (age, 56 ± 7 years; mean Model for End-Stage Liver Disease score, 22.6). They received LT 6 ± 3 months after enrollment and were re-evaluated 7 ± 3 months after LT with a stable course. A significant improvement in cognition with increase in microbial diversity, increase in autochthonous and decrease in potentially pathogenic taxa, and reduced endotoxemia were seen after LT compared with baseline. Stool BAs increased significantly after LT, and there was evidence of greater bacterial action (higher secondary, oxo and iso-BAs) after LT although the levels of conjugated BAs remained similar. There was a reduced serum ammonia and corresponding rise in urinary phenylacetylglutamine after LT. There was an increase in urinary trimethylamine-N-oxide, which was correlated with specific changes in serum lipids related to cell membrane products. The ultimate post-LT lipidomic profile appeared beneficial compared with the profile before LT. In conclusion, LT improves gut microbiota diversity and dysbiosis, which is accompanied by favorable changes in gut microbial functionality corresponding to BAs, ammonia, endotoxemia, lipidomic, and metabolomic profiles. Liver Transplantation 24 752-761 2018 AASLD.


Assuntos
Disbiose/microbiologia , Doença Hepática Terminal/cirurgia , Microbioma Gastrointestinal/fisiologia , Cirrose Hepática/cirurgia , Transplante de Fígado , Ácidos e Sais Biliares/sangue , Cognição/fisiologia , Disbiose/sangue , Disbiose/fisiopatologia , Doença Hepática Terminal/sangue , Doença Hepática Terminal/microbiologia , Endotoxemia/diagnóstico , Endotoxemia/microbiologia , Endotoxemia/fisiopatologia , Fezes/microbiologia , Feminino , Humanos , Metabolismo dos Lipídeos/fisiologia , Fígado/metabolismo , Fígado/cirurgia , Cirrose Hepática/sangue , Cirrose Hepática/microbiologia , Testes de Função Hepática , Masculino , Metaboloma/fisiologia , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Resultado do Tratamento
17.
Artif Cells Nanomed Biotechnol ; 46(3): 488-499, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-28503994

RESUMO

Pseudomonas aeruginosa and its lipopolysaccharides play a key role in the pathogenesis of diabetic foot infection, for which, currently no effective therapeutic agents are available. Hence, newer forms of therapeutic agents are required for treating Pseudomonas aeruginosa infection. In this present study, nanocrystalline silver nanoparticles (AgNPs) were synthesized using culture filtrate of Brevibacillus brevis KN8(2) followed by an investigation of its in vivo anti-pseudomonal and anti-endotoxic properties. Biosynthesized AgNPs was predominantly cubical in shape with an average particle size of 15.40 nm as observed through field emission scanning electron microscopy (FESEM) and X-ray diffraction analysis. The LC-ESI-MS/MS analysis indicates the presence of surfactin in culture filtrate of B. brevis KN8(2). The MIC of surfactin-stabilized AgNPs against P. aeruginosa was 10 µg ml-1 and its wound repair activity was observed in P. aeruginosa-infected wounds of diabetic mice by measuring wound area closure, bacterial counts, mRNA expressions, and histopathology. Further, surfactin-stabilized AgNPs suppressed the transcription of LPS-triggered expression of the TNF-α in wounds that LPS-assisted extension of wound repair in diabetes mellitus conditions was circumvented quite well. Results gathered in this study established that surfactin-stabilized AgNPs could effectively offer to the novel treatment of Gram-negative bacilli infection in diabetic wounds.


Assuntos
Antibacterianos/farmacologia , Diabetes Mellitus Experimental/tratamento farmacológico , Endotoxemia/tratamento farmacológico , Nanopartículas Metálicas/uso terapêutico , Infecções por Pseudomonas/tratamento farmacológico , Pseudomonas aeruginosa , Prata/farmacologia , Infecção dos Ferimentos/tratamento farmacológico , Animais , Antibacterianos/química , Diabetes Mellitus Experimental/microbiologia , Diabetes Mellitus Experimental/patologia , Endotoxemia/microbiologia , Endotoxemia/patologia , Masculino , Nanopartículas Metálicas/química , Camundongos , Infecções por Pseudomonas/patologia , Prata/química , Infecção dos Ferimentos/microbiologia , Infecção dos Ferimentos/patologia
18.
Eur J Nutr ; 57(3): 861-876, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28875318

RESUMO

INTRODUCTION: Nonalcoholic steatohepatitis (NASH) is characterized by the presence of steatosis, inflammation, and ballooning degeneration of hepatocytes, with or without fibrosis. The prevalence of NASH has increased with the obesity epidemic, but its etiology is multifactorial. The current studies suggest the role of gut microbiota in the development and progression of NASH. The aim is to review the studies that investigate the relationship between gut microbiota and NASH. These review also discusses the pathophysiological mechanisms and the influence of diet on the gut-liver axis. RESULT: The available literature has proposed mechanisms for an association between gut microbiota and NASH, such as: modification energy homeostasis, lipopolysaccharides (LPS)-endotoxemia, increased endogenous production of ethanol, and alteration in the metabolism of bile acid and choline. There is evidence to suggest that NASH patients have a higher prevalence of bacterial overgrowth in the small intestine and changes in the composition of the gut microbiota. However, there is still a controversy regarding the microbiome profile in this population. The abundance of Bacteroidetes phylum may be increased, decreased, or unaltered in NASH patients. There is an increase in the Escherichia and Bacteroides genus. There is depletion of certain taxa, such as Prevotella and Faecalibacterium. CONCLUSION: Although few studies have evaluated the composition of the gut microbiota in patients with NASH, it is observed that these individuals have a distinct gut microbiota, compared to the control groups, which explains, at least in part, the genesis and progression of the disease through multiple mechanisms. Modulation of the gut microbiota through diet control offers new challenges for future studies.


Assuntos
Disbiose/fisiopatologia , Medicina Baseada em Evidências , Microbioma Gastrointestinal , Fígado/fisiopatologia , Modelos Biológicos , Hepatopatia Gordurosa não Alcoólica/etiologia , Animais , Ácidos e Sais Biliares/metabolismo , Colina/metabolismo , Dieta/efeitos adversos , Progressão da Doença , Disbiose/imunologia , Disbiose/metabolismo , Disbiose/microbiologia , Endotoxemia/etiologia , Endotoxemia/imunologia , Endotoxemia/microbiologia , Endotoxemia/fisiopatologia , Ingestão de Energia , Metabolismo Energético , Etanol/metabolismo , Fermentação , Microbioma Gastrointestinal/imunologia , Humanos , Lipopolissacarídeos/biossíntese , Lipopolissacarídeos/toxicidade , Fígado/imunologia , Fígado/metabolismo , Hepatopatia Gordurosa não Alcoólica/imunologia , Hepatopatia Gordurosa não Alcoólica/microbiologia , Hepatopatia Gordurosa não Alcoólica/fisiopatologia
19.
Infect Immun ; 86(1)2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29061705

RESUMO

Postfermented Pu-erh tea (PE) protects against metabolic syndrome (MS), but little is known regarding its underlying mechanisms. Animal experiments were performed to determine whether the gut microbiota mediated the improvement in diet-induced MS by PE and its main active components (PEAC). We confirmed that PE altered the body composition and energy efficiency, attenuated metabolic endotoxemia and systemic and multiple-tissue inflammation, and improved the glucose and lipid metabolism disorder in high-fat diet (HFD)-fed mice via multiple pathways. Notably, PE promoted the lipid oxidation and browning of white adipose tissue (WAT) in HFD-fed mice. Polyphenols and caffeine (CAF) played critical roles in improving these parameters. Meanwhile, PE remodeled the disrupted intestinal homeostasis that was induced by the HFD. Many metabolic changes observed in the mice were significantly correlated with alterations in specific gut bacteria. Akkermansia muciniphila and Faecalibacterium prausnitzii were speculated to be the key gut bacterial links between the PEAC treatment and MS at the genus and species levels. Interestingly, A. muciniphila administration altered body composition and energy efficiency, promoted the browning of WAT, and improved the lipid and glucose metabolism disorder in the HFD-fed mice, whereas F. prausnitzii administration reduced the HFD-induced liver and intestinal inflammatory responses. In summary, polyphenol- and CAF-rich PE improved diet-induced MS, and this effect was associated with a remodeling of the gut microbiota.


Assuntos
Cafeína/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Homeostase/efeitos dos fármacos , Intestinos/efeitos dos fármacos , Síndrome Metabólica/tratamento farmacológico , Polifenóis/farmacologia , Chá/química , Animais , Linhagem Celular , Linhagem Celular Tumoral , Dieta Hiperlipídica/efeitos adversos , Endotoxemia/tratamento farmacológico , Endotoxemia/microbiologia , Células HEK293 , Células HeLa , Humanos , Inflamação/tratamento farmacológico , Inflamação/microbiologia , Intestinos/microbiologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microbiota/efeitos dos fármacos
20.
Int J Food Sci Nutr ; 69(2): 125-143, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28675945

RESUMO

Dietary fat strongly affects human health by modulating gut microbiota composition and low-grade systemic inflammation. High-fat diets have been implicated in reduced gut microbiota richness, increased Firmicutes to Bacteroidetes ratio, and several changes at family, genus and species levels. Saturated (SFA), monounsaturated (MUFA), polyunsaturated (PUFA) and conjugated linolenic fatty acids share important pathways of immune system activation/inhibition with gut microbes, modulating obesogenic and proinflammatory profiles. Mechanisms that link dietary fat, gut microbiota and obesity are mediated by increased intestinal permeability, systemic endotoxemia, and the activity of the endocannabinoid system. Although the probiotic therapy could be a complementary strategy to improve gut microbiota composition, it did not show permanent effects to treat fat-induced dysbiosis. Based upon evidence to date, we believe that high-fat diets and SFA consumption should be avoided, and MUFA and omega-3 PUFA intake should be encouraged in order to regulate gut microbiota and inflammation, promoting body weight/fat control.


Assuntos
Dieta Hiperlipídica/efeitos adversos , Disbiose/etiologia , Endotoxemia/etiologia , Enterite/etiologia , Medicina Baseada em Evidências , Intestinos/imunologia , Obesidade/etiologia , Animais , Disbiose/dietoterapia , Disbiose/microbiologia , Disbiose/fisiopatologia , Endotoxemia/imunologia , Endotoxemia/microbiologia , Endotoxemia/prevenção & controle , Enterite/imunologia , Enterite/microbiologia , Enterite/prevenção & controle , Microbioma Gastrointestinal , Humanos , Intestinos/microbiologia , Intestinos/fisiopatologia , Obesidade/imunologia , Obesidade/microbiologia , Obesidade/fisiopatologia , Permeabilidade , Probióticos/uso terapêutico , Simbióticos/administração & dosagem , Ganho de Peso
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