RESUMO
A range of antibiotic alternative products is increasingly studied and manufactured in the current animal agriculture, particularly in the poultry industry. Phytogenic feed additives are known for their remarkable ability to suppress pathogens such as Clostridium spp., Escherichia coli, and Salmonella. Other than enhancing biosecurity, improvements in productivity and performance were also observed. However, clear mechanisms for these improvements were not established. In this study, 20,000 Lohman-Brown layers were provided with phytogenic supplement from 16 to 40 weeks of age, and performance parameters were assessed against the same number of unsupplemented control birds. The performance results showed that the birds with phytogenic supplementation presented consistently reduced mortality, increased rate of lay, and increased average egg weight. Functional analysis through shotgun sequencing of cecal metagenomes confirmed a substantial functional shift in the microbial community, showing that phytogen significantly reduced the range of microbial functions, including the production of essential vitamins, cofactors, energy, and amino acids. Functional data showed that phytogen supplementation induced a phenotypic shift in intestinal bacteria LPS phenotype toward the less pathogenic form. The study corroborates the use of phytogenic products in antibiotic-free poultry production systems. The productivity improvements in the number and weight of eggs produced during Spotty Liver Disease justify further optimizing phytogenic alternatives for use in high-risk open and free-range poultry systems. IMPORTANCE The present study establishes the beneficial effects of the continuous phytogenic supplementation reflected in reduced diarrhea and mortality and higher egg productivity under normal conditions and during a natural outbreak of Spotty Liver Disease. Our data points to the importance of phytogen-driven alteration of microbial pathogenicity and fitness-related functional capabilities revealed on the commercial layer farm. Phytogenic product showed an ability to improve the bird's welfare and sustainability in free-range poultry production systems.
Assuntos
Galinhas , Hepatopatias , Aminoácidos , Ração Animal/análise , Animais , Bactérias , Galinhas/microbiologia , Lipopolissacarídeos , Hepatopatias/microbiologia , Aves Domésticas , Virulência , VitaminasRESUMO
Background: The gut-liver axis plays a crucial role in various liver diseases. Therefore, targeting this crosstalk may provide a new treatment strategy for liver diseases. However, the exact mechanism underlying this crosstalk and its impact on drug-induced liver injury (DILI) requires clarification. Aim: This study aimed to investigate the potential mechanism and therapeutic effect of MgIG on MTX-induced liver injury, which is associated with the gut-liver axis and gut microbiota. Methods: An MTX-induced liver injury model was generated after 20-mg/kg/3d MTX application for 30 days. Meanwhile, the treatment group was treated with 40-mg/kg MgIG daily. Histological examination, aminotransferase, and aspartate aminotransferase enzyme levels were estimated to evaluate liver function. Immune cells infiltration and inflammatory cytokines were detected to indicate inflammation levels. Colon histological score, intestinal barrier leakage, and expression of tight junctions were employed to assess the intestinal injury. Bacterial translocation was observed using fluorescent in situ hybridisation, colony-forming unit counting, and lipopolysaccharide detection. Alterations in gut microbial composition were analysed using 16s rDNA sequencing and relative quantitative polymerase chain reaction. Short-chain-fatty-acids and lactic acid concentrations were then utilized to validate changes in metabolites of specific bacteria. Lactobacillus sp. supplement and fecal microbiota transplantation were used to evaluate gut microbiota contribution. Results: MTX-induced intestinal and liver injuries were significantly alleviated using MgIG treatment. Bacterial translocation resulting from the intestinal barrier disruption was considered a crucial cause of MTX-induced liver injury and the therapeutic target of MgIG. Moreover, MgIG was speculated to have changed the gut microbial composition by up-regulating probiotic Lactobacillus and down-regulating Muribaculaceae, thereby remodelling the intestinal barrier and inhibiting bacterial translocation. Conclusion: The MTX-induced intestinal barrier was protected owing to MgIG administration, which reshaped the gut microbial composition and inhibited bacterial translocation into the liver, thus attenuating MTX-related DILI.
Assuntos
Doença Hepática Crônica Induzida por Substâncias e Drogas , Microbioma Gastrointestinal , Hepatopatias , Humanos , Hepatopatias/microbiologia , Metotrexato/efeitos adversos , Saponinas , TriterpenosRESUMO
Campylobacter hepaticus causes Spotty Liver Disease (SLD) in chickens. C. hepaticus is fastidious and slow-growing, presenting difficulties when growing this bacterium for the preparation of bacterin vaccines and experimental disease challenge trials. This study applied genomic analysis and in vitro experiments to develop an enhanced C. hepaticus liquid culture method. In silico analysis of the anabolic pathways encoded by C. hepaticus revealed that the bacterium is unable to biosynthesise L-cysteine, L-lysine and L-arginine. It was found that L-cysteine added to Brucella broth, significantly enhanced the growth of C. hepaticus, but L-lysine or L-arginine addition did not enhance growth. Brucella broth supplemented with L-cysteine (0.4 mM), L-glutamine (4 mM), and sodium pyruvate (10 mM) gave high-density growth of C. hepaticus and resulted in an almost tenfold increase in culture density compared to the growth in Brucella broth alone (log10 = 9.3 vs 8.4 CFU/mL). The type of culture flask used also significantly affected C. hepaticus culture density. An SLD challenge trial demonstrated that C. hepaticus grown in the enhanced culture conditions retained full virulence. The enhanced liquid culture method developed in this study enables the efficient production of bacterial biomass and therefore facilitates further studies of SLD biology and vaccine development.
Assuntos
Campylobacter/crescimento & desenvolvimento , Galinhas/microbiologia , Doenças das Aves Domésticas/microbiologia , Animais , Campylobacter/isolamento & purificação , Suplementos Nutricionais , Hepatopatias/microbiologia , Hepatopatias/veterináriaRESUMO
Chronic liver disease leads to neuropsychiatric complications called hepatic encephalopathy (HE). Current treatments have some limitations in their efficacy and tolerability, emphasizing the need for alternative therapies. Modulation of gut bacterial flora using probiotics is emerging as a therapeutic alternative. However, knowledge about how probiotics influence brain metabolite changes during HE is missing. In the present study, we combined the advantages of ultra-high field in vivo 1H MRS with behavioural tests to analyse whether a long-term treatment with a multistrain probiotic mixture (VIVOMIXX) in a rat model of type C HE had a positive effect on behaviour and neurometabolic changes. We showed that the prophylactic administration of this probiotic formulation led to an increase in gut Bifidobacteria and attenuated changes in locomotor activity and neurometabolic profile in a rat model of type C HE. Both the performance in behavioural tests and the neurometabolic profile of BDL + probiotic rats were improved compared to the BDL group at week 8 post-BDL. They displayed a significantly lesser increase in brain Gln, a milder decrease in brain mIns and a smaller decrease in neurotransmitter Glu than untreated animals. The clinical implications of these findings are potentially far-reaching given that probiotics are generally safe and well-tolerated by patients.
Assuntos
Encéfalo/metabolismo , Colestase/metabolismo , Hepatopatias/metabolismo , Probióticos/uso terapêutico , Compostos de Amônio/sangue , Animais , Comportamento Animal , Bifidobacterium/fisiologia , Ductos Biliares/patologia , Bilirrubina/sangue , Glicemia/metabolismo , Peso Corporal , Colestase/sangue , Colestase/microbiologia , Progressão da Doença , Fezes/microbiologia , Microbioma Gastrointestinal/efeitos dos fármacos , Glutamina/metabolismo , Inositol/metabolismo , Ligadura , Hepatopatias/sangue , Hepatopatias/microbiologia , Masculino , Metaboloma , Espectroscopia de Prótons por Ressonância Magnética , Ratos WistarRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Gut microbiome dysbiosis is closely associated with cholestatic liver disease. Huangqi decoction (HQD), a traditional herbal formula, has protection against cholestatic liver injury. However, the effect of HQD on gut microbiome remains unknown. AIM OF THE STUDY: To investigate the effect of HQD on 3, 5-diethoxycarbonyl-1, 4-dihydrocollidine (DDC) induced cholestatic liver injury and its effect on the gut microbiome profiles. MATERIALS AND METHODS: Mice with DDC-induced cholestatic liver injury were treated with low and high doses of HQD for 8 weeks. Fecal samples were analyzed by 16 S ribosomal DNA sequencing. Barrier function as well as intestinal and hepatic inflammation was analyzed by real-time PCR and western blotting. RESULTS: HQD treatment ameliorated the DDC-induced liver injury and collagen deposition around hepatic bile ducts. Moreover, decreased diversity, reduced richness, and abnormal composition of intestinal microbiota of cholestatic mice were remarkably attenuated by HQD supplementation. Differences in bacterial abundance, including levels of Prevotellaceae_NK3B31_group, Alistipes, and Gordonibacter, were increased in DDC-induced mice, as compared with control mice, and were decreased after HQD treatment. Moreover, intestinal dysbiosis promoted disruption of the intestinal barrier in cholestatic mice. However, HQD treatment alleviated intestinal barrier dysfunction. Importantly, increased hepatic expression of pro-inflammatory factors and the NLRP3 inflammasome, which have a positive correlation with differential bacteria, were characteristics found in DDC-induced cholestatic mice that were alleviated upon treatment with HQD. CONCLUSION: HQD treatment alleviated gut microbiota dysbiosis, ameliorated the intestinal barrier dysfunction, inhibited liver inflammation, and protected against DDC-induced cholestatic liver injury.
Assuntos
Bactérias/efeitos dos fármacos , Colestase/tratamento farmacológico , Colo/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Fármacos Gastrointestinais/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Hepatopatias/prevenção & controle , Fígado/efeitos dos fármacos , Animais , Astragalus propinquus , Bactérias/crescimento & desenvolvimento , Colestase/metabolismo , Colestase/microbiologia , Colestase/patologia , Colo/metabolismo , Colo/microbiologia , Citocinas/metabolismo , Modelos Animais de Doenças , Disbiose , Inflamassomos/metabolismo , Mediadores da Inflamação/metabolismo , Fígado/metabolismo , Fígado/patologia , Hepatopatias/metabolismo , Hepatopatias/microbiologia , Hepatopatias/patologia , Masculino , Camundongos Endogâmicos C57BL , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , PermeabilidadeRESUMO
In this study, we investigated the protective efficacy of extracellular polysaccharide from Cordyceps militaris (CEP-I) in liver and kidney and their regulating effect on gut microbiota against Pb-induced toxicity in vivo. The results indicated that CEP-I could reduce the Pb2+ content and organ index of liver and kidney in mice. Besides, biochemical analysis showed that CEP-I could improve the activity of glutathione peroxidase (GSH-Px), malondialdehyde (MDA) and superoxide dismutase (SOD) in serum and organs, restore the physiological indexes of total protein (TP), albumin (ALB), blood urea nitrogen (BUN) and creatinine (CRE) in serum and decrease the enzyme activity of lactate dehydrogenase (LDH) and aspartate aminotransferase (AST) in the liver and kidney of mice poisoned by Pb2+. This indicated that CEP-I has a protective effect on organs against damage in mice. In addition, CEP-I could regulate the expression of key proteins in the Nrf2 signaling pathway, including NF-E2-related factor 2 (Nrf2), Kelch-like ECH-associated protein-1 (Keap1), Heme oxygenase (HO-1) and NAD(P)H: quinone oxidoreductase 1 (NQO1). Furthermore, the intestinal flora analysis results indicated that CEP-I also has the capacity to regulate the intestinal flora imbalance caused by Pb2+ in poisoned mice. In conclusion, we hope that this study can provide theoretical basis for the treatment of tissue damage induced by Pb2+.
Assuntos
Cordyceps/química , Nefropatias/prevenção & controle , Chumbo/toxicidade , Hepatopatias/prevenção & controle , Fator 2 Relacionado a NF-E2/metabolismo , Extratos Vegetais/administração & dosagem , Polissacarídeos/administração & dosagem , Animais , Microbioma Gastrointestinal , Glutationa Peroxidase/genética , Glutationa Peroxidase/metabolismo , Humanos , Rim/efeitos dos fármacos , Rim/metabolismo , Nefropatias/genética , Nefropatias/metabolismo , Nefropatias/microbiologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Hepatopatias/genética , Hepatopatias/metabolismo , Hepatopatias/microbiologia , Masculino , Malondialdeído/metabolismo , Camundongos , Fator 2 Relacionado a NF-E2/genética , Estresse Oxidativo/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismoRESUMO
The association of habitual coffee consumption with a lower risk of diseases, like type 2 diabetes mellitus, chronic liver disease, certain cancer types, or with reduced all-cause mortality, has been confirmed in prospective cohort studies in many regions of the world. The molecular mechanism is still unresolved. The radical-scavenging and anti-inflammatory activity of coffee constituents is too weak to account for such effects. We argue here that coffee as a plant food has similar beneficial properties to many vegetables and fruits. Recent studies have identified a health promoting mechanism common to coffee, vegetables and fruits, i.e., the activation of an adaptive cellular response characterized by the upregulation of proteins involved in cell protection, notably antioxidant, detoxifying and repair enzymes. Key to this response is the activation of the Nrf2 (Nuclear factor erythroid 2-related factor-2) system by phenolic phytochemicals, which induces the expression of cell defense genes. Coffee plays a dominant role in that regard because it is the major dietary source of phenolic acids and polyphenols in the developed world. A possible supportive action may be the modulation of the gut microbiota by non-digested prebiotic constituents of coffee, but the available data are still scarce. We conclude that coffee employs similar pathways of promoting health as assumed for other vegetables and fruits. Coffee beans may be viewed as healthy vegetable food and a main supplier of dietary phenolic phytochemicals.
Assuntos
Antioxidantes/farmacologia , Coffea/química , Café , Dieta , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/farmacologia , Antioxidantes/uso terapêutico , Dano ao DNA/efeitos dos fármacos , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/microbiologia , Diabetes Mellitus Tipo 2/prevenção & controle , Microbioma Gastrointestinal/efeitos dos fármacos , Humanos , Hepatopatias/metabolismo , Hepatopatias/microbiologia , Hepatopatias/prevenção & controle , Fator 2 Relacionado a NF-E2/metabolismo , Neoplasias/metabolismo , Neoplasias/microbiologia , Neoplasias/prevenção & controle , Compostos Fitoquímicos/uso terapêutico , Extratos Vegetais/uso terapêutico , Polifenóis/farmacologia , Polifenóis/uso terapêutico , PrebióticosRESUMO
BACKGROUND: Systemic inflammation and severe fibrosis can reduce serum zinc levels, while zinc supplementation is reported to improve the prognosis of patients with chronic liver disease (CLD). OBJECTIVES: We aimed to investigate the clinical application of serum zinc in patients with CLD and the anti-infective mechanism of zinc supplementation. METHODS: Based on the serum zinc level, 149 CLD patients were divided into 3 groups and their clinical parameters were compared. In in-vitro experiments, microbial isolates derived from patients were used to stimulate human liver non-parenchymal cells, and the zinc sulfate solution was added in certain experiments. The effect of zinc was compared by LDH and thromboxane A2 levels in the cell supernatant. RESULT: Compared with other groups, patients with low serum zinc levels had significantly higher C-reactive protein (CRP), total bilirubin, INR, creatinine, and MELD scores, while albumin and GOT levels were reduced. Only CRP and albumin were significantly correlated with serum zinc in both low and normal-zinc groups. Bacterial isolates significantly increased LDH levels in Kupffer cells (KCs) and stellate cells but had no effect on sinusoidal endothelial cells, whereas zinc pretreatment protected KCs but not stellate cells. Thromboxane A2 secreted by KCs can also be induced by bacterial stimulation, accompanied by increased gene expression of Myd88, MAPK and NF-kB, while zinc pretreatment can attenuate that. CONCLUSION: Serum zinc levels can be used to estimate infection and liver fibrosis in CLD patients. As a new antibacterial weapon, zinc supplementation acts on KCs through Myd88-MAPK related pathways.
Assuntos
Células de Kupffer/metabolismo , Cirrose Hepática/tratamento farmacológico , Hepatopatias/tratamento farmacológico , Sulfato de Zinco/administração & dosagem , Adulto , Idoso , Doença Crônica , Feminino , Regulação da Expressão Gênica , Células Estreladas do Fígado/metabolismo , Humanos , Cirrose Hepática/microbiologia , Cirrose Hepática/fisiopatologia , Hepatopatias/microbiologia , Hepatopatias/fisiopatologia , Masculino , Pessoa de Meia-Idade , Tromboxano A2/metabolismo , Zinco/sangue , Sulfato de Zinco/farmacologiaAssuntos
Microbioma Gastrointestinal/fisiologia , Hepatopatias/microbiologia , Hepatopatias/terapia , Terapia por Fagos , Animais , Bacteriófagos/fisiologia , Etanol/metabolismo , Fígado Gorduroso Alcoólico/genética , Fígado Gorduroso Alcoólico/microbiologia , Fígado Gorduroso Alcoólico/patologia , Fígado Gorduroso Alcoólico/terapia , Transplante de Microbiota Fecal/métodos , Predisposição Genética para Doença , Humanos , Klebsiella pneumoniae/metabolismo , Klebsiella pneumoniae/virologia , Hepatopatias/genética , Camundongos , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/microbiologia , Hepatopatia Gordurosa não Alcoólica/patologia , Hepatopatia Gordurosa não Alcoólica/terapia , Distúrbios Nutricionais/complicações , Distúrbios Nutricionais/genética , Distúrbios Nutricionais/microbiologia , Distúrbios Nutricionais/prevenção & controle , Terapia por Fagos/métodos , Saccharomyces/metabolismoRESUMO
Elevated circulating level of the intestinal microbiota-derived l-carnitine metabolite trimethylamine-N-oxide (TMAO) has recently been linked to many chronic diseases. The purpose of our study was to investigate the effects of omega-7-enriched Decaisnea insignis seed oil (DISO) on reducing TMAO formation to prevent the l-carnitine-induced hepatic damage in mice. Feeding of mice with 3% l-carnitine in drinking water clearly increased the serum and urinary levels of TMAO (p < 0.05 vs Normal), whereas the serum and urinary TMAO formation was sharply reduced by DISO administration (p < 0.05). Meanwhile, DISO resulted in strong inhibition against the elevation of hepatic injury marker (AST, ALT, and ALP) activities and dyslipidemia (TC, TG, LDL-C, and HDL-C), as well as liver inflammatory cytokine (IL-1, IL-6, TNF-α, and TNF-ß) release in l-carnitine-fed mice (p < 0.05). As revealed by 16S rDNA gene sequencing, DISO significantly inhibited the l-carnitine-induced elevations in the abundance of Firmicutes, Proteobacteria, and Erysipelotrichaceae and the increases in the proportion of Lactobacillus and Akkermansia, revealing that DISO attenuated the l-carnitine-caused gut dysbiosis. These findings suggested that DISO could alleviate liver dysfunction in l-carnitine-fed mice, which might be due to the protection against TMAO formation by modulating the gut microbiota.
Assuntos
Carnitina/efeitos adversos , Microbioma Gastrointestinal/efeitos dos fármacos , Hepatopatias/tratamento farmacológico , Magnoliopsida/química , Óleos de Plantas/farmacologia , Animais , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Humanos , Interleucina-1/genética , Interleucina-1/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Hepatopatias/metabolismo , Hepatopatias/microbiologia , Masculino , Metilaminas/efeitos adversos , Camundongos , Sementes/químicaRESUMO
Increased global regulation and restrictions on the non-therapeutic use of antibiotics in the poultry industry means that there is a need to identify alternatives that prevent infection while still conveying the growth and performance benefits afforded by their use. Biochars are produced by the incomplete pyrolysis of organic materials, with reports of use as a feed supplement and activity against pathogenic bacteria. In the current study the dose-dependent effects of biochar dietary inclusion in layer diets at 1%, 2% and 4% w/w were investigated to determine a) the efficacy of biochar as an anti-pathogenic additive on the intestinal microbiota and b) the optimal inclusion level. Biochar inclusion for anti-pathogenic effects was found to be most beneficial at 2% w/w. Poultry pathogens such as Gallibacterium anatis and campylobacters, including Campylobacter hepaticus, were found to be significantly lower in biochar fed birds. A shift in microbiota was also associated with the incorporation of 2% w/w biochar in the feed in two large scale trials on two commercial layer farms. Biochar inclusion for anti-pathogenic effects was found to be most beneficial at 2% w/w. Differential effects of the timing of biochar administration (supplementation beginning at hatch or at point of lay) were also evident, with greater impact on community microbial structure at 48 weeks of age when birds were fed from hatch rather than supplemented at point of lay.
Assuntos
Ração Animal , Infecções por Campylobacter/veterinária , Campylobacter , Carvão Vegetal/química , Hepatopatias/veterinária , Doenças das Aves Domésticas/prevenção & controle , Ciências da Nutrição Animal , Animais , Infecções por Campylobacter/prevenção & controle , Galinhas/microbiologia , Suplementos Nutricionais , Feminino , Microbioma Gastrointestinal , Hepatopatias/microbiologia , Hepatopatias/prevenção & controle , Microbiota , Doenças das Aves Domésticas/microbiologiaRESUMO
BACKGROUND: Probiotics can be viewed as biological agents that modify the intestinal microbiota and certain cytokine profiles, which can lead to an improvement in certain gastrointestinal diseases, including diarrhea, inflammatory bowel disease, and liver disease. DISCUSSION: Consumption of probiotics in their various forms, including yogurt, functional foods, and dietary supplements, is frequently encountered worldwide. Often, however, the correct prescription of these agents is dampened due to a lack of knowledge of the scientific evidence and the different presentations and microbial compositions of the currently available probiotic options. Here, we provide an up-to-date review of the evidence of probiotics in the prevention and treatment of various gastrointestinal diseases. OBJECTIVE: Consumption of probiotics in their various forms, including yogurt, functional foods, and dietary supplements, is frequently encountered worldwide. Often, however, the correct prescription of these agents is dampened due to a lack of knowledge of the scientific evidence and the different presentations and microbial compositions of the currently available probiotic options. METHODS/RESULTS: Here, we provide an up-to-date review of the evidence of probiotics in the prevention and treatment of various gastrointestinal diseases. CONCLUSION: While not efficacious in every disease process studied, probiotics have demonstrated some benefit in several specific gastrointestinal and liver diseases.
Assuntos
Gastroenteropatias/dietoterapia , Hepatopatias/dietoterapia , Probióticos/uso terapêutico , Dieta , Suplementos Nutricionais , Gastroenteropatias/microbiologia , Microbioma Gastrointestinal/fisiologia , Trato Gastrointestinal/microbiologia , Humanos , Doenças Inflamatórias Intestinais/dietoterapia , Doenças Inflamatórias Intestinais/microbiologia , Hepatopatias/microbiologia , IogurteAssuntos
Ciprofloxacina/farmacocinética , Ciprofloxacina/uso terapêutico , Cistos/tratamento farmacológico , Cistos/microbiologia , Hepatopatias/tratamento farmacológico , Hepatopatias/microbiologia , Rim Policístico Autossômico Dominante/complicações , Antibacterianos/farmacocinética , Antibacterianos/uso terapêutico , Ciprofloxacina/farmacologia , Humanos , Resultado do TratamentoRESUMO
AIM: To investigate gut microbial diversity and the interventional effect of Xiaoyaosan (XYS) in a rat model of functional dyspepsia (FD) with liver depression-spleen deficiency syndrome. METHODS: The FD with liver depression-spleen deficiency syndrome rat model was established through classic chronic mild unpredictable stimulation every day. XYS group rats received XYS 1 h before the stimulation. The models were assessed by parameters including state of the rat, weight, sucrose test result and open-field test result. After 3 wk, the stools of rats were collected and genomic DNA was extracted. PCR products of the V4 region of 16S rDNA were sequenced using a barcoded Illumina paired-end sequencing technique. The primary composition of the microbiome in the stool samples was determined and analyzed by cluster analysis. RESULTS: Rat models were successfully established, per data from rat state, weight and open-field test. The microbiomes contained 20 phyla from all samples. Firmicutes, Bacteroidetes, Proteobacteria, Cyanobacteria and Tenericutes were the most abundant taxonomic groups. The relative abundance of Firmicutes, Proteobacteria and Cyanobacteria in the model group was higher than that in the normal group. On the contrary, the relative abundance of Bacteroidetes in the model group was lower than that in the normal group. Upon XYS treatment, the relative abundance of all dysregulated phyla was restored to levels similar to those observed in the normal group. Abundance clustering heat map of phyla corroborated the taxonomic distribution. CONCLUSION: The microbiome relative abundance of FD rats with liver depression-spleen deficiency syndrome was significantly different from the normal cohort. XYS intervention may effectively adjust the gut dysbacteriosis in FD.
Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Dispepsia/tratamento farmacológico , Dispepsia/microbiologia , Microbioma Gastrointestinal/genética , Animais , Modelos Animais de Doenças , Dispepsia/etiologia , Sequenciamento de Nucleotídeos em Larga Escala , Hepatopatias/microbiologia , Masculino , Ratos , Ratos Sprague-Dawley , Esplenopatias/microbiologia , SíndromeRESUMO
The gut microbiome is composed of a vast number of microbes in the gastrointestinal tract, which benefit host metabolism, aid in digestion, and contribute to normal immune function. Alterations in microbial composition can result in intestinal dysbiosis, which has been implicated in several diseases including obesity, inflammatory bowel disease, and liver diseases. Over the past several years, significant interactions between the intestinal microbiota and liver have been discovered, with possible mechanisms for the development as well as progression of liver disease and promising therapeutic targets to either prevent or halt the progression of liver disease. In this review the authors examine mechanisms of dysbiosis-induced liver disease; highlight current knowledge regarding the role of dysbiosis in nonalcoholic liver disease, alcoholic liver disease, and cirrhosis; and discuss potential therapeutic targets.
Assuntos
Antibacterianos/uso terapêutico , Suplementos Nutricionais , Disbiose , Transplante de Microbiota Fecal , Microbioma Gastrointestinal , Trato Gastrointestinal/microbiologia , Hepatopatias/terapia , Fígado/microbiologia , Animais , Antibacterianos/efeitos adversos , Suplementos Nutricionais/efeitos adversos , Transplante de Microbiota Fecal/efeitos adversos , Interações Hospedeiro-Patógeno , Humanos , Hepatopatias/diagnóstico , Hepatopatias/microbiologia , Prebióticos , Probióticos/uso terapêutico , Simbióticos , Resultado do TratamentoRESUMO
Enterococcal infections are common in liver transplantation and hepatopancreaticobiliary (HPB) surgery. Linezolid is frequently used to treat not only vancomycin-resistant Enterococcus (VRE), but also vancomycin-sensitive Enterococcus (VSE) infections, and resistance can develop. This study evaluated all the Liver Unit patients who developed infections with linezolid-resistant Enterococcus (LRE) in order to elicit the association with prior linezolid usage, to explore possible risk factors for infection, and to better understand the epidemiology of these isolates in this patient group. Between 2010 and 2015, infections with LRE developed in 10 patients (8 following liver transplantation and 2 following HPB surgery) after 22-108 days of treatment. Selected pulsed-field gel electrophoresis demonstrated that 2 out of 10 patients were cocolonized with different strains and indicated that cross-transmission may have occurred. In conclusion, in this group of patients with complex hepatobiliary infections, the optimal antibiotic strategies for the treatment of Enterococcus faecium infections are not clearly defined, and there is a significant risk of emergence of resistance to linezolid in E. faecium after exposure to this agent in patients, especially in the presence of a deep source of infection on a background of hepatic artery insufficiency. Caution is needed when using prolonged courses of linezolid in this setting, and further studies are necessary to determine the optimum treatment.
Assuntos
Farmacorresistência Bacteriana , Enterococcus faecium , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Linezolida/uso terapêutico , Hepatopatias/microbiologia , Transplante de Fígado/efeitos adversos , Adulto , Idoso , Antibacterianos/uso terapêutico , Sistema Biliar/microbiologia , Doenças Biliares/cirurgia , Infecção Hospitalar , Eletroforese em Gel de Campo Pulsado , Feminino , Seguimentos , Humanos , Imunossupressores , Fígado/microbiologia , Hepatopatias/cirurgia , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Adulto JovemRESUMO
OBJECTIVE: The objective of this study is to develop a nanostructured parenteral delivery system, laden with curcumin (CUR), for the therapeutic intervention of sepsis and associated pathologies. METHODS: Nanoemulsions were fabricated using sonication and speed homogenization. Size and zeta potential were evaluated by dynamic light scattering and transmission electron microscopy analysis. Pharmacodynamic and pharmacokinetic studies were performed on a rat model of lipopolysaccharide (LPS)-induced sepsis. RESULTS: The drug content of optimized nanoemulsion (F5) formulation (particle size 246 ± 08 nm, polydispersity index (PDI) of 0.120, zeta potential of -41.1 ± 1.2 mV) was found to be 1.25 mg/ml. In vitro release studies demonstrated that F5 was able to sustain the release of CUR for up to 24 h. Minimal hemolysis and cellular toxicity demonstrated its suitability for intravenous administration. Significant reduction of inflammatory mediator levels was mediated through enhanced uptake by in RAW 264.7 and THP-1 in absence/presence of LPS. Nanoemulsion resulted in an improvement of plasma concentration (AUCF5/AUC CUR = 8.80) and tissue distribution of CUR in rats leading to a reduction in LPS-induced lung and liver injury due to less neutrophil migration, reduced TNF-α levels and oxidative stress (demonstrated by levels of lipid peroxides as well as carbonylated proteins) as confirmed by histopathological studies. CONCLUSION: The findings suggest that the therapeutic performance (i.e., reduction in oxidative damage in tissues) of CUR can be enhanced by employing tocol acetate nanoemulsions (via improving pharmacokinetics and tissue distribution) as a platform for drug delivery in sepsis-induced organ injury.
Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Curcumina/administração & dosagem , Modelos Animais de Doenças , Sistemas de Liberação de Medicamentos , Sepse/tratamento farmacológico , Vitaminas/química , alfa-Tocoferol/química , Animais , Anti-Inflamatórios não Esteroides/farmacocinética , Linhagem Celular , Curcumina/farmacocinética , Citocinas/sangue , Portadores de Fármacos , Emulsões/química , Ensaio de Imunoadsorção Enzimática , Escherichia coli , Citometria de Fluxo , Infusões Parenterais , Peróxidos Lipídicos/metabolismo , Lipopolissacarídeos , Hepatopatias/sangue , Hepatopatias/tratamento farmacológico , Hepatopatias/microbiologia , Masculino , Nanopartículas/química , Edema Pulmonar/sangue , Edema Pulmonar/tratamento farmacológico , Edema Pulmonar/microbiologia , Ratos , Ratos Sprague-Dawley , Sepse/sangue , Sepse/microbiologia , Distribuição TecidualRESUMO
Zinc is a trace element vital for immune function during host response to infection. The proinsulin C-peptide has been shown to exert beneficial effects through activation of the anti-inflammatory peroxisome proliferator-activated receptor γ (PPARγ) in experimental endotoxemia. Some in vitro activities of C-peptide appear dependent on the presence of zinc. We investigated the effect of zinc supplementation before onset of sepsis on the anti-inflammatory properties of C-peptide. Male C57BL/6 mice were subjected to polymicrobial sepsis by cecal ligation and puncture (CLP). Mice received zinc gluconate (1.3 mg/kg) intraperitoneally (i.p.) for 3 days before CLP. One hour after CLP, animals received C-peptide (280 nmol/kg i.p.) or the antimicrobial agent imipenem (25 mg/kg i.p.). Cecal ligation and puncture was associated with an 11% survival rate, pulmonary leukosequestration, and liver injury. Molecular analysis in lungs of septic mice showed increased nuclear activation of the proinflammatory extracellular signal-regulated kinases 1 and 2 and nuclear factor κB, but decreased PPARγ expression, when compared with sham animals. Combination of zinc supplementation with C-peptide posttreatment significantly improved survival rate (61%) similarly to antibiotic treatment (60%), ameliorated lung architecture and liver function, reduced tissue neutrophil infiltration, and increased bacterial clearance when compared with vehicle, C-peptide, or zinc treatment alone. These beneficial effects were associated with restored lung nuclear expression of PPARγ and reduction of phosphorylated extracellular signal-regulated kinases 1 and 2 and nuclear factor κB activities in comparison to vehicle or single treatment protocols. Our data demonstrate that short-term zinc prophylaxis before the infectious insult is a requisite for the anti-inflammatory properties of C-peptide by facilitating modulation of inflammatory pathways.
Assuntos
Peptídeo C/uso terapêutico , Suplementos Nutricionais , Sepse/tratamento farmacológico , Síndrome de Resposta Inflamatória Sistêmica/prevenção & controle , Zinco/uso terapêutico , Lesão Pulmonar Aguda/prevenção & controle , Animais , Carga Bacteriana/efeitos dos fármacos , Líquido da Lavagem Broncoalveolar/citologia , Citocinas/sangue , Avaliação Pré-Clínica de Medicamentos/métodos , Quimioterapia Combinada , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Hepatopatias/microbiologia , Hepatopatias/prevenção & controle , Masculino , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Infiltração de Neutrófilos/efeitos dos fármacos , Sepse/complicações , Sepse/metabolismo , Sepse/microbiologia , Análise de Sobrevida , Síndrome de Resposta Inflamatória Sistêmica/metabolismo , Síndrome de Resposta Inflamatória Sistêmica/microbiologiaRESUMO
While a central role for the microbiota in the precipitation of infectious and non-infectious complications of liver disease has been long established, evidence for a more fundamental role in the etiology of several liver diseases continues to accumulate. However, though progress is rapidly occurring in this area, the definitive delineation of the precise relevance of changes in the microbiota to various forms and stages of liver disease is still far from complete. While high quality clinical evidence supports the use of antibiotic therapy, in the management of hepatic encephalopathy, spontaneous bacterial peritonitis and other infectious complications, how these interventions impact on the microbiota and microbiota-host interactions has not been clearly defined. Although probiotics and even, perhaps, fecal transplantation hold promise in the management of liver disease, and the potential impact of probiotics is supported by a considerable amount of laboratory data, high-quality clinical evidence is scanty.
Assuntos
Intestinos/microbiologia , Hepatopatias/microbiologia , Fígado/microbiologia , Microbiota , Antibacterianos/uso terapêutico , Terapia Biológica , Fezes/microbiologia , Encefalopatia Hepática/microbiologia , Interações Hospedeiro-Patógeno , Humanos , Intestinos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Hepatopatias/diagnóstico , Hepatopatias/terapia , Peritonite/microbiologia , Probióticos/uso terapêutico , Fatores de Risco , Resultado do TratamentoRESUMO
GC-MS analysis of a hot water extract of Herba Pogostemonis (HP) revealed the presence of 131 compounds. HP slightly inhibited Salmonella Typhimurium bacteria in culture and stimulated uptake of the bacteria into RAW 264.7 murine macrophage cells as indicated by both increased fluorescence from internalized FITC-dextran and increased colony-forming unit (CFU) counts of the lysed macrophages. Postinfection, the HP-treated cells showed lower bacterial counts than the control. HP elicited altered morphology, elevated inducible NO synthase (iNOS) mRNA, and reduced pro-inflammatory cytokine expression in macrophage cells. Salmonella induced increased expression of iNOS mRNA, cognate polypeptides, and NO. Histology of mice infected with a sublethal dose (1 × 10(4) CFU) of Salmonella showed that intraperitoneally administered HP protected against necrosis of the liver, a biomarker of in vivo salmonellosis. The lifespan of mice infected with a lethal dose (1 × 10(5) CFU) was significantly extended. These results suggest that the activity of HP against bacterial infection in mice occurs through the activation of innate immune macrophage cells. The relationship of composition of HP to bioactivity is discussed.