RESUMEN
Recent evidence indicates that liver cirrhosis (LC) is a reversible condition, but there is no established intervention against liver fibrosis. Although the gut microbiota is considered involved in the pathogenesis of LC, the underlying mechanisms remain unclear. Although the antibiotic, rifaximin (RFX), is effective for hepatic encephalopathy (HE) with LC, the impact of RFX on intestinal bacteria is unknown. We investigated the bacterial compositions along the GI tract under RFX treatment using a murine LC model. RFX improved liver fibrosis and hyperammonemia and altered the bacterial composition in the small intestine. The efficacy of RFX was associated with increases in specific bacterial genera, including Akkermansia. Administration of a commensal strain of Akkermansia muciniphila improved liver fibrosis and hyperammonemia with changing bacterial composition in the small intestine. This study proposed a new concept "small intestine-liver axis" in the pathophysiology of LC and oral A. muciniphila administration is a promising microbial intervention.
Asunto(s)
Akkermansia , Modelos Animales de Enfermedad , Microbioma Gastrointestinal , Intestino Delgado , Cirrosis Hepática , Rifaximina , Animales , Ratones , Intestino Delgado/microbiología , Intestino Delgado/patología , Cirrosis Hepática/microbiología , Rifaximina/uso terapéutico , Rifaximina/farmacología , Microbioma Gastrointestinal/efectos de los fármacos , Masculino , Verrucomicrobia , Ratones Endogámicos C57BL , Hígado/patología , Hígado/microbiología , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , ARN Ribosómico 16S/genéticaRESUMEN
The gut microbiota drives progression to liver fibrosis, the main determinant of mortality in metabolic dysfunction-associated steatohepatitis (MASH). In this study, we aimed to identify bacterial species associated with protection against liver fibrosis in a high-risk population, and test their potential to protect against liver fibrosis in vivo. Based on stool shotgun metagenomic sequencing of 340 subjects from a population cohort disproportionally affected by MASH, we identified bacterial species from the Bacteroidales and Clostridiales orders associated with reduced risk of liver fibrosis. A bacterial consortium was subsequently tested in a mouse model of MASH, which demonstrated protective effects against liver fibrosis. Six of the eight inoculated bacteria were detected in mouse stool and liver. Intrahepatic presence of bacteria was further confirmed by bacterial culture of mouse liver tissue. Changes in liver histological parameters, gut functional profiles, and amino acid profiles were additionally assessed. Comparison between fibrosis-associated human metagenome and bacteria-induced metagenome changes in mice identified microbial functions likely to mediate the protective effect against liver fibrosis. Amino acid profiling confirmed an increase in cysteine synthase activity, associated with reduced fibrosis. Other microbiota-induced changes in amino acids associated with reduced fibrosis included increased gut asparaginase activity and decreased hepatic tryptophan-to-kynurenine conversion. This human-to-mouse study identified bacterial species and their effects on amino acid metabolism as innovative strategies to protect against liver fibrosis in MASH.
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Aminoácidos , Bacterias , Microbioma Gastrointestinal , Cirrosis Hepática , Hígado , Animales , Humanos , Cirrosis Hepática/microbiología , Cirrosis Hepática/metabolismo , Ratones , Aminoácidos/metabolismo , Bacterias/clasificación , Bacterias/metabolismo , Bacterias/genética , Bacterias/aislamiento & purificación , Masculino , Hígado/metabolismo , Hígado/patología , Hígado/microbiología , Femenino , Heces/microbiología , Ratones Endogámicos C57BL , Persona de Mediana Edad , Hígado Graso/metabolismo , Hígado Graso/microbiología , Modelos Animales de Enfermedad , Metagenoma , AdultoRESUMEN
Newly synthesized vaccines prepared from formalin-killed bacteria Streptococcus pyogenes were investigated in the current study to evaluate the effectiveness of the newly synthesized vaccine as well as their safety by injected intraperitoneal. The study involved several steps 1st step is the preparation of the vaccine followed by the 2nd step: Evaluate the effectiveness and vaccine safety against pathogenic S. pyogenes through 4 different groups including control (Group I). Group II (Bacterial, infected group), Group III (Vaccine), and the Last group was the challenged group after the vaccination (Vacc + Bac). Different Immunological and biochemical parameters were measured in addition to hematological and histopathological examinations. For example, oxidative/antioxidants, inflammatory biomarkers, fragmentation and cell damage, and finally the histopathological study. The current study showed an increase in all oxidative, inflammatory, and cell damage (DNA fragmentation assays), additionally markedly elevation in histopathological cell damage in the infected group (Group II) compared with the control group. The vaccine and challenged after vaccination group (vaccine + Bacteria), showed great improvement in oxidative biomarkers (LPO) and an increase in antioxidants biomarkers (GSH, SOD, GST, DPPH, ABTS, GR and GPx), Also the inflammation and histopathological examination. The newly synthesized vaccine improved the resistance of Oreochromis niloticus and can be used as a preventive therapy agent for pathogenic bacteria S. pyogenes.
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Cíclidos , Hígado , Infecciones Estreptocócicas , Vacunas Estreptocócicas , Streptococcus pyogenes , Vacunación , Animales , Streptococcus pyogenes/inmunología , Infecciones Estreptocócicas/prevención & control , Infecciones Estreptocócicas/inmunología , Cíclidos/inmunología , Cíclidos/microbiología , Hígado/microbiología , Hígado/patología , Hígado/metabolismo , Vacunación/métodos , Vacunas Estreptocócicas/inmunología , Formaldehído , Vacunas de Productos Inactivados/inmunología , Enfermedades de los Peces/prevención & control , Enfermedades de los Peces/microbiología , Enfermedades de los Peces/inmunología , Antioxidantes/farmacología , Estrés Oxidativo/efectos de los fármacos , BiomarcadoresRESUMEN
Helicobacter pylori infection has been thought to be associated with liver diseases, although the exact mechanisms remain elusive. This study identified H. pylori-induced liver inflammation and tissue damage in infected mice and examined the exosome-mediated mechanism underlying H. pylori infection's impact on liver injury. Exosomes were isolated from H. pylori-infected gastric epithelial GES-1 cells (Hp-GES-EVs), and the crucial virulence factor CagA was identified within these exosomes. Fluorescent labeling demonstrated that Hp-GES-EVs can be absorbed by liver cells. Treatment with Hp-GES-EVs enhanced the proliferation, migration, and invasion of Hep G2 and Hep 3B cells. Additionally, exposure to Hp-GES-EVs activated NF-κB and PI3K/AKT signaling pathways, which provides a reasonable explanation for the liver inflammation and neoplastic traits. Using a mouse model established via tail vein injection of Hp-GES-EVs, exosome-driven liver injury was evidenced by slight hepatocellular erosion around the central hepatic vein and elevated serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and IL-6. Administering the exosome inhibitor GW4869 via intraperitoneal injection in mice resulted in a reduction of liver damage caused by H. pylori infection. These findings illuminate the exosome-mediated pathogenesis of H. pylori-induced liver injury and offer valuable insights into the extra-gastrointestinal manifestations of H. pylori infection.
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Antígenos Bacterianos , Proteínas Bacterianas , Modelos Animales de Enfermedad , Exosomas , Infecciones por Helicobacter , Helicobacter pylori , Hígado , Transducción de Señal , Exosomas/metabolismo , Animales , Infecciones por Helicobacter/complicaciones , Infecciones por Helicobacter/microbiología , Infecciones por Helicobacter/metabolismo , Helicobacter pylori/patogenicidad , Ratones , Humanos , Proteínas Bacterianas/metabolismo , Hígado/patología , Hígado/metabolismo , Hígado/microbiología , Antígenos Bacterianos/metabolismo , Compuestos de Bencilideno/farmacología , Compuestos de Anilina/farmacología , FN-kappa B/metabolismo , Células Hep G2 , Aspartato Aminotransferasas/sangre , Interleucina-6/metabolismo , Alanina Transaminasa/sangre , Proliferación Celular , Proteínas Proto-Oncogénicas c-akt/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Células Epiteliales/microbiología , Células Epiteliales/metabolismo , Movimiento Celular , Línea Celular , Masculino , Factores de Virulencia/metabolismoRESUMEN
The ISS rodent habitat has provided crucial insights into the impact of spaceflight on mammals, inducing symptoms characteristic of liver disease, insulin resistance, osteopenia, and myopathy. Although these physiological responses can involve the microbiome on Earth, host-microbiota interactions during spaceflight are still being elucidated. We explore murine gut microbiota and host gene expression in the colon and liver after 29 and 56 days of spaceflight using multiomics. Metagenomics revealed significant changes in 44 microbiome species, including relative reductions in bile acid and butyrate metabolising bacteria like Extibacter muris and Dysosmobacter welbionis. Functional prediction indicate over-representation of fatty acid and bile acid metabolism, extracellular matrix interactions, and antibiotic resistance genes. Host gene expression described corresponding changes to bile acid and energy metabolism, and immune suppression. These changes imply that interactions at the host-gut microbiome interface contribute to spaceflight pathology and that these interactions might critically influence human health and long-duration spaceflight feasibility.
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Bacterias , Microbioma Gastrointestinal , Vuelo Espacial , Animales , Ratones , Bacterias/clasificación , Bacterias/genética , Hígado/microbiología , Interacciones Microbiota-Huesped , Metagenómica/métodos , Colon/microbiología , Ácidos y Sales Biliares/metabolismo , Metabolismo Energético , Masculino , Humanos , Ratones Endogámicos C57BLRESUMEN
BACKGROUND: Multiple factors are involved in the pathogenesis of primary biliary cholangitis (PBC), a chronic cholestatic liver disease, characterized by intrahepatic cholangiopathy. In particular, studies have suggested that environmental factors such as the presence of granulomas in the portal vein region are important for the development of PBC. This study aimed to comprehensively analyze and identify foreign-derived antigens in PBC liver tissue to confirm their involvement in PBC pathogenesis. METHODS: Portal areas and hepatocyte regions were selectively dissected from formalin-fixed paraffin-embedded PBC liver tissue samples using the microlaser method, followed by total DNA extraction. We then validated whether the bacterial strains identified through 16S rRNA metagenomic analysis were detected in PBC liver tissues. RESULTS: The most frequently detected bacterial genera in the PBC liver tissue samples were Sphingomonas panacis, Providencia, and Cutibacterium. These bacterial genera were also detected in the other PBC samples. Validation for the detection of S. panacis, the most abundant genus, revealed polymerase chain reaction bands extracted from the portal areas of all samples. They were also more highly expressed than bands detected in the hepatocyte region. CONCLUSION: S. panacis antigen was specifically detected in the portal areas of PBC liver tissues. The introduction of foreign-derived antigens into the liver as an environmental factor could be a possible mechanism for the development of PBC.
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Cirrosis Hepática Biliar , Hígado , ARN Ribosómico 16S , ARN Ribosómico 16S/genética , Humanos , Hígado/microbiología , Hígado/patología , Cirrosis Hepática Biliar/microbiología , Cirrosis Hepática Biliar/genética , Metagenoma , Antígenos Bacterianos/genética , Femenino , Masculino , Persona de Mediana Edad , Metagenómica/métodos , Bacterias/genética , Bacterias/clasificación , Bacterias/aislamiento & purificación , AncianoRESUMEN
The role of the gut microbiota in the occurrence and progression of primary biliary cholangitis (PBC) is not fully understood. First, the fecal microbiota of patients with PBC (n = 4) (PBC-FMT) or healthy individuals (n = 3) (HC-FMT) was transplanted into pseudo germ-free mice or 2OA-BSA-induced PBC models. The functions, histology and transcriptome of the liver, and microbiota and metabolome of the feces were analyzed. Second, the liver transcriptomes of PBC patients (n = 7) and normal individuals (n = 7) were analyzed. Third, the liver transcriptomes of patients with other liver diseases were collected from online databases and compared with our human and mouse data. Our results showed that PBC-FMT increased the serum ALP concentration, total bile acid content, liver injury and number of disease-related pathways enriched with upregulated liver genes in pseudo germ-free mice and increased the serum glycylproline dipeptidyl aminopeptidase level and liver damage in a 2OA-BSA-induced PBC model. The gut microbiota and metabolome differed between PBC-FMT and HC-FMT mice and reflected those of their donors. PBC-FMT tended to upregulate hepatic immune and signal transduction pathways but downregulate metabolic pathways, as in some PBC patients. The hematopoietic cell lineage, Toll-like receptor, and PPAR signaling pathway were not affected in patients with alcoholic hepatitis, HBV, HCV, HCV cirrhosis, or NASH, indicating their potential roles in the gut microbiota affecting PBC. In conclusion, the altered gut microbiota of PBC patients plays an important role in the occurrence and progression of PBC. The improvement of the gut microbiota is worthy of in-depth research and promotion as a critical aspect of PBC prevention and treatment.
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Modelos Animales de Enfermedad , Heces , Microbioma Gastrointestinal , Cirrosis Hepática Biliar , Hígado , Animales , Humanos , Ratones , Cirrosis Hepática Biliar/microbiología , Cirrosis Hepática Biliar/patología , Cirrosis Hepática Biliar/metabolismo , Hígado/patología , Hígado/metabolismo , Hígado/microbiología , Heces/microbiología , Femenino , Bacterias/clasificación , Bacterias/aislamiento & purificación , Bacterias/genética , Trasplante de Microbiota Fecal , Masculino , Ácidos y Sales Biliares/metabolismo , Transcriptoma , Ratones Endogámicos C57BLRESUMEN
Akkermansia muciniphila (A. muciniphila) is a 'star strain' that has attracted much attention in recent years. A. muciniphila can effectively regulate host metabolism, significantly affect host immune function, and play an important role in balancing host health and disease. As one of the organs most closely related to the gut (the two can communicate through the hepatic portal vein and bile duct system), liver is widely affected by intestinal microorganisms. A growing body of evidence suggests that A. muciniphila may alleviate liver-related diseases by improving the intestinal barrier, energy metabolism and regulating inflammation through its protein components and metabolites. This paper systematically reviews the key roles of A. muciniphila and its derivatives in maintaining liver health and improving liver disease.
[Box: see text].
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Akkermansia , Microbioma Gastrointestinal , Hígado , Humanos , Akkermansia/fisiología , Hígado/microbiología , Hígado/metabolismo , Microbioma Gastrointestinal/fisiología , Animales , Hepatopatías/microbiología , Verrucomicrobia/fisiología , ProbióticosRESUMEN
Alcohol-associated liver disease is a leading cause of chronic liver conditions, yet there are limited effective therapies. In this issue of Cell Host & Microbe, Shen et al. demonstrate that soluble dietary fiber enhances intestinal Bacteroides acidifaciens, which ameliorates alcohol-associated liver injury in mice by activating hepatic ornithine aminotransferase.
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Bacteroides , Hígado , Animales , Ratones , Hígado/microbiología , Hígado/metabolismo , Fibras de la Dieta/metabolismo , Humanos , Hepatopatías Alcohólicas/microbiología , Hepatopatías Alcohólicas/metabolismo , Microbioma GastrointestinalRESUMEN
A taxogenomic study of three strains (3986T, 51.81, and JF 2415) isolated from rabbits between 1972 and 2000 led to the description of a new Neisseria species. The highest sequence similarity of the 16S rRNA gene was found to Neisseria animalis NCTC 10212T (96.7â%). The 16S rRNA gene similarity above 99â% and average nucleotide identity (ANI) values above 96â% among the strains, indicated that they belong to the same species. At the same time, the strains shared ANI values below 81â% and dDDH values below 24â% with all described Neisseria species. In the bac120 gene phylogenetic tree, the three strains clustered near Neisseria elongata and Neisseria bacilliformis in the Neisseria clade. However, the Neisseria clade is not monophyletic, and includes the type strains of Morococcus cerebrosus, Bergeriella denitrificans, Kingella potus, Uruburuella suis, and Uruburuella testudinis. Neisseria shayeganii clustered outside the clade with members of the genus Eikenella. Amino acid identity (AAI) values were calculated, and a threshold of 71â% was used to circumscribe the genus Neisseria. According to this proposed AAI threshold, strains 3986T, 51.81, and JF 2415 were placed within the genus Neisseria. The cells of the three strains were Gram-stain-negative diplococcobacilli and non-motile. Optimal growth on trypticase soy agar occurred at 37 °C and pH 8.5 in aerobic conditions. Notably, all strains exhibited indole production in the API-NH test, which is atypical for Neisseria and the family Neisseriaceae. The strains exhibited a common set of 68 peaks in their MALDI-TOF MS profiles, facilitating the swift and accurate identification of this species. Based on genotypic and phenotypic data, it is proposed that strains 3986T, 51.81, and JF 2415 represent a novel species within the genus Neisseria, for which the name Neisseria leonii sp. nov. is proposed (type strain 3986T=R726T=CIP 109994T=LMG 32907T).
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Técnicas de Tipificación Bacteriana , ADN Bacteriano , Hígado , Pulmón , Neisseria , Filogenia , ARN Ribosómico 16S , Análisis de Secuencia de ADN , Animales , Conejos , ARN Ribosómico 16S/genética , Neisseria/aislamiento & purificación , Neisseria/clasificación , Neisseria/genética , ADN Bacteriano/genética , Hígado/microbiología , Pulmón/microbiología , Ácidos Grasos/análisis , Composición de BaseRESUMEN
The objective of our study was to evaluate the effect of endophyte-infected tall fescue (E+) seeds intake on liver tissue transcriptome in growing Angus × Simmental steers and heifers through RNA-seq analysis. Normal weaned calves (~8 months old) received either endophyte-free tall fescue (E-; n = 3) or infected tall fescue (E+; n = 6) seeds for a 30-d period. The diet offered was ad libitum bermudagrass (Cynodon dactylon) hay combined with a nutritional supplement of 1.61 kg (DM basis) of E+ or E- tall fescue seeds, and 1.61 kg (DM basis) of energy/protein supplement pellets for a 30-d period. Dietary E+ tall fescue seeds were included in a rate of 20 µg of ergovaline/kg BW/day. Liver tissue was individually obtained through biopsy at d 30. After preparation and processing of the liver samples for RNA sequencing, we detected that several metabolic pathways were activated (i.e., upregulated) by the consumption of E+ tall fescue. Among them, oxidative phosphorylation, ribosome biogenesis, protein processing in endoplasmic reticulum and apoptosis, suggesting an active mechanism to cope against impairment in normal liver function. Interestingly, hepatic protein synthesis might increase due to E+ consumption. In addition, there was upregulation of "thermogenesis" KEGG pathway, showing a possible increase in energy expenditure in liver tissue due to consumption of E+ diet. Therefore, results from our study expand the current knowledge related to liver metabolism of growing beef cattle under tall fescue toxicosis.
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Alimentación Animal , Endófitos , Hígado , Semillas , Animales , Bovinos , Semillas/microbiología , Hígado/metabolismo , Hígado/microbiología , Alimentación Animal/análisis , Transcriptoma , Femenino , Masculino , Festuca/microbiología , Perfilación de la Expresión Génica , Ergotaminas/metabolismoRESUMEN
The microbiota significantly impacts digestive epithelium functionality, especially in nutrient processing. Given the importance of iron for both the host and the microbiota, we hypothesized that host-microbiota interactions fluctuate with dietary iron levels. We compared germ-free (GF) and conventional mice (SPF) fed iron-containing (65 mg/Kg) or iron-depleted (<6 mg/Kg) diets. The efficacy of iron privation was validated by iron blood parameters. Ferritin and Dmt1, which represent cellular iron storage and transport respectively, were studied in tissues where they are abundant: the duodenum, liver and lung. When the mice were fed an iron-rich diet, the microbiota increased blood hemoglobin and hepcidin and the intestinal ferritin levels, suggesting that the microbiota helps iron storage. When iron was limiting, the microbiota inhibited the expression of the intestinal Dmt1 transporter, likely via the pathway triggered by Hif-2α. The microbiota assists the host in storing intestinal iron when it is abundant and competes with the host by inhibiting Dmt1 in conditions of iron scarcity. Comparison between duodenum, liver and lung indicates organ-specific responses to microbiota and iron availability. Iron depletion induced temporal changes in microbiota composition and activity, reduced α-diversity of microbiota, and led to Lactobacillaceae becoming particularly more abundant after 60 days of privation. By inoculating GF mice with a simplified bacterial mixture, we show that the iron-depleted host favors the gut fitness of Bifidobacterium longum.
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Proteínas de Transporte de Catión , Duodeno , Microbioma Gastrointestinal , Hepcidinas , Hierro de la Dieta , Hígado , Animales , Ratones , Microbioma Gastrointestinal/fisiología , Hierro de la Dieta/metabolismo , Hierro de la Dieta/administración & dosificación , Proteínas de Transporte de Catión/metabolismo , Proteínas de Transporte de Catión/genética , Hígado/metabolismo , Hígado/microbiología , Duodeno/metabolismo , Duodeno/microbiología , Hepcidinas/metabolismo , Ferritinas/metabolismo , Vida Libre de Gérmenes , Interacciones Microbiota-Huesped , Pulmón/microbiología , Pulmón/metabolismo , Hierro/metabolismo , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Bacterias/clasificación , Bacterias/metabolismo , Bacterias/genética , Bacterias/aislamiento & purificación , Ratones Endogámicos C57BL , Hemoglobinas/metabolismo , MasculinoRESUMEN
Despite the observed decrease in liver fat associated with metabolic-associated fatty liver disease (MAFLD) in mice following fecal microbiota transplantation, the clinical effects and underlying mechanisms of washed microbiota transplantation (WMT), a refined method of fecal microbiota transplantation, for the treatment of MAFLD remain unclear. In this study, both patients and mice with MAFLD exhibit an altered gut microbiota composition. WMT increases the levels of beneficial bacteria, decreases the abundance of pathogenic bacteria, and reduces hepatic steatosis in MAFLD-affected patients and mice. Downregulation of the liver-homing chemokine receptor CXCR6 on ILC3s results in an atypical distribution of ILC3s in patients and mice with MAFLD, characterized by a significant reduction in ILC3s in the liver and an increase in ILC3s outside the liver. Moreover, disease severity is negatively correlated with the proportion of hepatic ILC3s. These hepatic ILC3s demonstrate a mitigating effect on hepatic steatosis through the release of IL-22. Mechanistically, WMT upregulates CXCR6 expression on ILC3s, thereby facilitating their migration to the liver of MAFLD mice via the CXCL16/CXCR6 axis, ultimately contributing to the amelioration of MAFLD. Overall, these findings highlight that WMT and targeting of liver-homing ILC3s could be promising strategies for the treatment of MAFLD.
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Quimiocina CXCL16 , Trasplante de Microbiota Fecal , Microbioma Gastrointestinal , Hígado , Receptores CXCR6 , Animales , Receptores CXCR6/metabolismo , Quimiocina CXCL16/metabolismo , Ratones , Humanos , Hígado/metabolismo , Hígado/microbiología , Linfocitos/inmunología , Linfocitos/metabolismo , Ratones Endogámicos C57BL , Masculino , Inmunidad Innata , Hígado Graso/terapia , Hígado Graso/metabolismo , Hígado Graso/microbiología , Interleucina-22 , Enfermedad del Hígado Graso no Alcohólico/terapia , Enfermedad del Hígado Graso no Alcohólico/microbiología , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Enfermedad del Hígado Graso no Alcohólico/inmunología , Interleucinas/metabolismo , FemeninoRESUMEN
Yeasts are unicellular eukaryotic microorganisms extensively employed in various applications, notably as an alternative source of protein in feeds, owing to their nutritional benefits. Despite their potential, marine and mangrove yeast species used in the aquaculture industry have received little attention in the Philippines. Pichia kudriavzevii (A2B R1 ISO 3), sourced from bark samples, was selected and mass-produced due to its high protein content and amino acid profile. The dried biomass of P. kudriavzevii was incorporated into the diets of Nile tilapia (Oreochromis niloticus) juveniles at varying inclusion levels (0, 1, 2, and 4 g/kg diet) and its effect on their growth performance, body composition, and liver and intestinal morphology was assessed after 40 days of feeding. The groups that received P. kudriavzevii at a concentration of 2 g/kg diet exhibited higher final body weight, percent weight gain, and specific growth rate in comparison to the other treatment groups. Whole body proximate composition did not vary among the dietary groups. Intestinal and liver histopathology also indicated no abnormalities. These findings suggest the potential of ascomycetous P. kudriavzevii as a beneficial feed additive in Nile tilapia diets, warranting further investigation into its long-term effects and broader applications in fish culture.
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Alimentación Animal , Acuicultura , Cíclidos , Pichia , Animales , Alimentación Animal/análisis , Cíclidos/crecimiento & desarrollo , Cíclidos/microbiología , Pichia/crecimiento & desarrollo , Pichia/aislamiento & purificación , Pichia/metabolismo , Dieta/veterinaria , Hígado/microbiología , Intestinos/microbiología , Suplementos Dietéticos/análisis , FilipinasRESUMEN
Hepatic steatosis is the initial manifestation of abnormal liver functions and often leads to liver diseases such as nonalcoholic fatty liver disease in humans and fatty liver syndrome in animals. In this study, we conducted a comprehensive analysis of a large chicken population consisting of 705 adult hens by combining host genome resequencing; liver transcriptome, proteome, and metabolome analysis; and microbial 16S ribosomal RNA gene sequencing of each gut segment. The results showed the heritability (h2 = 0.25) and duodenal microbiability (m2 = 0.26) of hepatic steatosis were relatively high, indicating a large effect of host genetics and duodenal microbiota on chicken hepatic steatosis. Individuals with hepatic steatosis had low microbiota diversity and a decreased genetic potential to process triglyceride output from hepatocytes, fatty acid ß-oxidation activity, and resistance to fatty acid peroxidation. Furthermore, we revealed a molecular network linking host genomic variants (GGA6: 5.59-5.69 Mb), hepatic gene/protein expression (PEMT, phosphatidyl-ethanolamine N-methyltransferase), metabolite abundances (folate, S-adenosylmethionine, homocysteine, phosphatidyl-ethanolamine, and phosphatidylcholine), and duodenal microbes (genus Lactobacillus) to hepatic steatosis, which could provide new insights into the regulatory mechanism of fatty liver development.
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Pollos , Hígado Graso , Microbioma Gastrointestinal , Animales , Pollos/microbiología , Microbioma Gastrointestinal/genética , Hígado Graso/genética , Hígado Graso/microbiología , Hígado Graso/veterinaria , Hígado Graso/metabolismo , Hígado/metabolismo , Hígado/microbiología , Transcriptoma , Genoma , Metaboloma , Enfermedades de las Aves de Corral/microbiología , Enfermedades de las Aves de Corral/genéticaRESUMEN
Evidence has indicated that Enterococcus plays a vital role in non-alcoholic fatty liver disease (NAFLD) development. However, the microbial genetic basis and metabolic potential in the disease are yet unknown. We previously isolated a bacteria Enterococcus faecium B6 (E. faecium B6) from children with NAFLD for the first time. Here, we aim to systematically investigate the potential of strain B6 in lipogenic effects. The lipogenic effects of strain B6 were explored in vitro and in vivo. The genomic and functional characterizations were investigated by whole-genome sequencing and comparative genomic analysis. Moreover, the metabolite profiles were unraveled by an untargeted metabolomic analysis. We demonstrated that strain B6 could effectively induce lipogenic effects in the liver of mice. Strain B6 contained a circular chromosome and two circular plasmids and posed various functions. Compared to the other two probiotic strains of E. faecium, strain B6 exhibited unique functions in pathways of ABC transporters, phosphotransferase system, and amino sugar and nucleotide sugar metabolism. Moreover, strain B6 produced several metabolites, mainly enriched in the protein digestion and absorption pathway. The unique potential of strain B6 in lipogenic effects was probably associated with glycolysis, fatty acid synthesis, and glutamine and choline transport. This study pioneeringly revealed the metabolic characteristics and specific detrimental traits of strain B6. The findings provided new insights into the underlying mechanisms of E. faecium in lipogenic effects, and laid essential foundations for further understanding of E. faecium-related disease.
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Enterococcus faecium , Lipogénesis , Enterococcus faecium/genética , Enterococcus faecium/metabolismo , Animales , Ratones , Lipogénesis/genética , Metabolómica/métodos , Enfermedad del Hígado Graso no Alcohólico/microbiología , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Enfermedad del Hígado Graso no Alcohólico/genética , Hígado/metabolismo , Hígado/microbiología , Masculino , Genoma Bacteriano , Probióticos , Secuenciación Completa del Genoma , Humanos , Genómica/métodos , Metaboloma , Ratones Endogámicos C57BLRESUMEN
Cholestasis is a common morbid state that may occur in different phases; however, a comprehensive evaluation of the long-term effect post-recovery is still lacking. In the hepatic cholestasis mouse model, which was induced by a temporary complete blockage of the bile duct, the stasis of bile acids and liver damage typically recovered within a short period. However, we found that the temporary hepatic cholestasis had a long-term effect on gut microbiota dysbiosis, including overgrowth of small intestinal bacteria, decreased diversity of the gut microbiota, and an overall imbalance in its composition accompanied by an elevated inflammation level. Additionally, we observed an increase in Escherichia-Shigella (represented by ASV136078), rich in virulence factors, in both small and large intestines following cholestasis. To confirm the causal role of dysregulated gut microbiota in promoting hepatic inflammation and injury, we conducted gut microbiota transplantation into germ-free mice. We found that recipient mice transplanted with feces from cholestasis mice exhibited liver inflammation, damage, and accumulation of hepatic bile acids. In conclusion, our study demonstrates that cholestasis disrupts the overall load and structural composition of the gut microbiota in mice, and these adverse effects persist after recovery from cholestatic liver injury. This finding suggests the importance of monitoring the structural composition of the gut microbiota in patients with cholestasis and during their recovery. IMPORTANCE: Our pre-clinical study using a mouse model of cholestasis underscores that cholestasis not only disrupts the equilibrium and structural configuration of the gut microbiota but also emphasizes the persistence of these adverse effects even after bile stasis restoration. This suggests the need of monitoring and initiating interventions for gut microbiota structural restoration in patients with cholestasis during and after recovery. We believe that our study contributes to novel and better understanding of the intricate interplay among bile acid homeostasis, gut microbiota, and cholestasis-associated complications. Our pre-clinical findings may provide implications for the clinical management of patients with cholestasis.
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Ácidos y Sales Biliares , Colestasis , Disbiosis , Microbioma Gastrointestinal , Ratones Endogámicos C57BL , Animales , Microbioma Gastrointestinal/fisiología , Ácidos y Sales Biliares/metabolismo , Colestasis/microbiología , Colestasis/metabolismo , Ratones , Disbiosis/microbiología , Masculino , Hígado/metabolismo , Hígado/microbiología , Hígado/patología , Modelos Animales de EnfermedadRESUMEN
This study aimed to assess the molecular prevalence of mite-borne zoonotic pathogen O. tsutsugamushi in household rats of South India through nested polymerase chain reaction amplification of O. tsutsugamushi 47-kDa htrA gene and to determine the most suitable sample type for screening of O. tsutsugamushi in rats. Out of 85 rats trapped in Tamil Nadu, Karnataka, and Puducherry regions, 47 rats were found positive for the O. tsutsugamushi genome with prevalence of 55.29â¯%. Among different sample types screened, faecal samples exhibited the highest positivity rate, followed by liver, spleen, kidney, and blood samples. Agreement between faecal and spleen samples of rats for the presence of O. tsutsugamushi was the highest. Principal component analysis revealed a positive correlation between the spleen, liver, and faeces and a negative correlation between blood and faeces for the presence of O. tsutsugamushi genome. These findings underscore the varied distribution of O. tsutsugamushi among different samples and indicate that the faecal and liver samples of rats are an ideal choice of samples for epidemiological studies. This is the first study to report a high level of presence of O. tsutsugamushi in faecal samples of rats.
Asunto(s)
Heces , Orientia tsutsugamushi , Tifus por Ácaros , Bazo , Animales , Orientia tsutsugamushi/genética , Orientia tsutsugamushi/aislamiento & purificación , India/epidemiología , Tifus por Ácaros/epidemiología , Tifus por Ácaros/microbiología , Ratas , Heces/microbiología , Estudios Transversales , Prevalencia , Bazo/microbiología , Hígado/microbiología , Enfermedades de los Roedores/epidemiología , Enfermedades de los Roedores/microbiología , Reacción en Cadena de la Polimerasa , ADN Bacteriano/genéticaRESUMEN
Salmonella and Campylobacter are major foodborne pathogens that cause outbreaks associated with contaminated chicken liver. Proper cooking is necessary to avoid the risk of illness to consumers. This study tested the thermal inactivation of a 4-strain Salmonella cocktail and a 3-strain Campylobacter cocktail in chicken livers separately at temperatures ranging from 55.0 to 62.5°C. Inoculated livers were sealed in aluminum cells and immersed in a water bath. The decimal reduction time (D-values) of Salmonella in chicken livers were 9.01, 2.36, 0.82, and 0.23 min at 55.0, 57.5, 60.0, and 62.5°C, respectively. The D-values of Campylobacter ranged from 2.22 min at 55.0°C to 0.19 min at 60.0°C. Salmonella and Campylobacter had similar z-values in chicken livers of 4.8 and 4.6°C, respectively. Chicken livers can be heated to internal temperatures of 70.0 to 73.9°C for at least 1.6 to 0.2 s to achieve a 7-log reduction of Salmonella. Validation tests demonstrated that heating chicken livers to internal temperatures of 70.0 to 73.9°C for 2 to 0 s resulted in a reduction of Salmonella exceeding 7 logs. Collectively, these data show that Salmonella exhibits higher heat resistance than Campylobacter in chicken livers. Therefore, Salmonella could be considered as the target pathogen when designing thermal treatments or cooking instructions for liver products. These findings will aid in designing effective thermal processing for both industrial and home cooking to eliminate Salmonella and Campylobacter, ensuring consumer safety when consuming chicken liver products.
Asunto(s)
Campylobacter , Pollos , Microbiología de Alimentos , Calor , Hígado , Salmonella , Animales , Campylobacter/fisiología , Hígado/microbiología , Salmonella/fisiología , Cinética , CulinariaRESUMEN
Transposon sequencing (Tn-seq) is a powerful genome-wide technique to assess bacterial fitness under varying growth conditions. However, screening via Tn-seq in vivo is challenging. Dose limitations and host restrictions create bottlenecks that diminish the transposon mutant pool being screened. Here, we have developed a murine model with a disruption in Akr1c13 that renders the resulting RECON-/- mouse resistant to high-dose infection. We leveraged this model to perform a Tn-seq screen of the human pathogen Listeria monocytogenes in vivo. We identified 135 genes which were required for L. monocytogenes growth in mice including novel genes not previously identified for host survival. We identified organ-specific requirements for L. monocytogenes survival and investigated the role of the folate enzyme FolD in L. monocytogenes liver pathogenesis. A mutant lacking folD was impaired for growth in murine livers by 2.5-log10 compared to wild type and failed to spread cell-to-cell in fibroblasts. In contrast, a mutant in alsR, which encodes a transcription factor that represses an operon involved in D-allose catabolism, was attenuated in both livers and spleens of mice by 4-log10 and 3-log10, respectively, but showed modest phenotypes in in vitro models. We confirmed that dysregulation of the D-allose catabolism operon is responsible for the in vivo growth defect, as deletion of the operon in the ∆alsR background rescued virulence. By undertaking an unbiased, genome-wide screen in mice, we have identified novel fitness determinants for L. monocytogenes host infection, which highlights the utility of the RECON-/- mouse model for future screening efforts. IMPORTANCE: Listeria monocytogenes is the gram-positive bacterium responsible for the food-borne disease listeriosis. Although infections with L. monocytogenes are limiting in healthy hosts, vulnerable populations, including pregnant and elderly people, can experience high rates of mortality. Thus, understanding the breadth of genetic requirements for L. monocytogenes in vivo survival will present new opportunities for treatment and prevention of listeriosis. We developed a murine model of infection using a RECON-/- mouse that is restrictive to systemic L. monocytogenes infection. We utilized this model to screen for L. monocytogenes genes required in vivo via transposon sequencing. We identified the liver-specific gene folD and a repressor, alsR, that only exhibits an in vivo growth defect. AlsR controls the expression of the D-allose operon which is a marker in diagnostic techniques to identify pathogenic Listeria. A better understanding of the role of the D-allose operon in human disease may further inform diagnostic and prevention measures.