• Hepatocyte
• MASLD
• Metabolic diseases
• Metabolome
• Microbiome
• RNAseq

• Humans
• Male
• Female
• Liver/metabolism
• Middle Aged
• Insulin Resistance
• Hippurates/metabolism
• Gastrointestinal Microbiome/physiology
• Lipid Metabolism
• Adult
• Obesity/metabolism
• Fatty Liver/metabolism
• Fatty Liver/microbiology
• Metabolome
• Metabolomics/methods
• Diabetes Mellitus, Type 2/metabolism

• Cirrhosis
• Gut microbiota
• Hepatic encephalopathy
• Hepatitis B virus
• Portal hypertension
• Transjugular intrahepatic portosystemic shunt

• Humans
• Gastrointestinal Microbiome
• Hypertension, Portal/microbiology
• Hypertension, Portal/surgery
• Hypertension, Portal/virology
• Hypertension, Portal/etiology
• Portasystemic Shunt, Transjugular Intrahepatic/adverse effects
• Hepatic Encephalopathy/microbiology
• Hepatic Encephalopathy/etiology
• Hepatic Encephalopathy/diagnosis
• Liver Cirrhosis/virology
• Liver Cirrhosis/microbiology
• Liver Cirrhosis/surgery
• Hepatitis B virus/pathogenicity
• Hepatitis B/complications
• Dysbiosis

• gut samples
• liver transplantation
• microbial composition
• microbial diversity
• microbiome
• pathobionts

• Humans
• Liver Transplantation/adverse effects
• Male
• Female
• Gastrointestinal Microbiome/drug effects
• Middle Aged
• Anti-Bacterial Agents/therapeutic use
• End Stage Liver Disease/surgery
• Follow-Up Studies
• Prognosis
• Adult
• Feces/microbiology
• Dysbiosis/microbiology
• Dysbiosis/etiology
• Severity of Illness Index
• Bacteria/isolation & purification
• Bacteria/genetics
• Bacteria/classification
• Postoperative Complications/microbiology
• Case-Control Studies
• Graft Survival
• Aged
• Tissue Donors

• enteric nervous system (ENS)
• intestinal organoids
• myenteric neurons
• pluripotent stem cells (PSCs)
• submucosal neurons
• three-dimensional (3D)

• Enteric Nervous System
• Organoids
• Humans
• Coculture Techniques/methods
• Gastrointestinal Diseases/pathology
• Gastrointestinal Diseases/therapy
• Animals
• Models, Biological
• Neurons/metabolism
• Intestines

• P30AR073761 NIAMS NIH HHS
• 8998GA American Association for the Study of Liver Diseases
• P30 DK120515 NIDDK NIH HHS
• D34HP31027 UC San Diego's Hispanic Center of Excellence
• R01 AA029106 NIAAA NIH HHS
• P30 AR073761 NIAMS NIH HHS
• R21 AA030654 NIAAA NIH HHS
• 1R21AA030654-01A1 NIAAA NIH HHS
• P30 DK048522 NIDDK NIH HHS
• P50 AA011999 NIAAA NIH HHS
• R01 AA029106-01A1 NIAAA NIH HHS

• dysbiosis
• fascioliasis
• gut microbiota

• A-068-2020 Peruvian University of Applied Sciences

• Biejiajian Pill
• Chinese medicine
• chronic hepatitis B
• intestinal microbiota
• liver cirrhosis
• liver fibrosis
• randomized controlled trial

• Humans
• Gastrointestinal Microbiome
• Prospective Studies
• Liver Cirrhosis/complications
• Liver Cirrhosis/drug therapy
• Hepatitis B/complications
• Hepatitis B/drug therapy

• bacterial translocation
• cirrhosis
• gut permeability
• inflammation
• microbiota

• Instituto de Salud Carlos III
• Ministerio de Ciencia e Innovación
• Conselleria de Cultura, Educación y Ciencia, Generalitat Valenciana

Human aging, a natural process characterized by structural and physiological changes, leads to alterations of homeostatic mechanisms, decline of biological functions, and subsequently, the organism becomes vulnerable to external stress or damage. In fact, the elderly population is prone to develop diseases due to deterioration of physiological and biological systems. With aging, the production of reactive oxygen species (ROS) increases, and this causes lipid, protein, and DNA damage, leading to cellular dysfunction and altered cellular processes. Indeed, oxidative stress plays a key role in the pathogenesis of several chronic disorders, including hepatic diseases, such as non-alcoholic fatty liver disease (NAFLD). NAFLD, the most common liver disorder in the Western world, is characterized by intrahepatic lipid accumulation; is highly prevalent in the aging population; and is closely associated with obesity, insulin resistance, hypertension, and dyslipidemia. Among the risk factors involved in the pathogenesis of NAFLD, the dysbiotic gut microbiota plays an essential role, leading to low-grade chronic inflammation, oxidative stress, and production of various toxic metabolites. The intestinal microbiota is a dynamic ecosystem of microbes involved in the maintenance of physiological homeostasis; the alteration of its composition and function, during aging, is implicated in different liver diseases. Therefore, gut microbiota restoration might be a complementary approach for treating NAFLD. The administration of probiotics, which can relieve oxidative stress and elicit several anti-aging properties, could be a strategy to modify the composition and restore a healthy gut microbiota. Indeed, probiotics could represent a valid supplement to prevent and/or help treating some diseases, such as NAFLD, thus improving the already available pharmacological intervention. Moreover, in aging, intervention of prebiotics and fecal microbiota transplantation, as well as probiotics, will provide novel therapeutic approaches. However, the relevant research is limited, and several scientific research works need to be done in the near future to confirm their efficacy.

• NAFLD
• age-related disease
• liver
• microbiota
• therapeutic strategies

• dysbiosis
• gut microbiota
• hepatocellular carcinoma
• prebiotics
• probiotics
• synbiotics

• Shanxi Provincial Key Research and Development Project
• Natural Science Foundation of Shanxi Province

• Ministry of Science and Technology, Taiwan

• urban ecology
• nutrition
• microbiota

• Humans
• Feces/microbiology
• Gardening
• Soil Microbiology
• Adult
• Male
• Child
• Female
• Adolescent
• Child, Preschool
• Gastrointestinal Microbiome
• Bacteria/classification
• Bacteria/genetics
• Bacteria/isolation & purification
• Case-Control Studies
• Microbiota
• Phylogeny
• Middle Aged

• Family Resilience Center at University of Illinois Urbana Champaign

• Intestinal microbiota
• acute cholestasis
• bile acids
• gene expression
• germ-free mice
• metabolism

• chronic hepatitis C
• colon microbiocenosis
• liver fibrosis
• pancreas

• Humans
• Dysbiosis/complications
• Dysbiosis/microbiology
• Hepatitis C, Chronic/complications
• Constipation
• Liver Cirrhosis/complications
• Pancreatic Elastase
• Escherichia coli
• Colon/microbiology
• Diarrhea
• Body Weight

Chronic hepatitis B virus infection is a source of substantial global health problems, particularly in economically underdeveloped and/or developing countries. It is the primary cause of severe liver disorders such as liver fibrosis, cirrhosis, and hepatocellular carcinoma. The liver is connected by the bile duct to the small intestine that carries bile produced in the liver to the intestine. The liver is the initial organ exposed to materials originating from the gut including dietary compounds, bacteria, and their products. Human intestines harbor a wide diversity of the community of microbes which are collectively termed as gut microbiota. In chronic infection with the hepatitis B virus, microbial alteration of the gut is a source of systemic immune activation. Besides, gut permeability is altered in hepatitis B virus-infected patients with an increased bacterial translocation and endotoxin load in the portal vein that caused toll-like receptor activation in the liver, which facilitates immune-mediated liver injury. Toll-like receptors further triggered the host-wide inflammatory response by inducing signaling cascades such as nuclear factor-kappa B-linked pathways and by accelerating cytokine secretion like tumor necrosis factor-alpha, which evokes chronic inflammation and leads to liver lesion formation, fibrosis progression, and cirrhosis and hepatocellular carcinoma development. In conclusion, changes in intestinal flora play an important role in encouraging the production of chronic infection with the hepatitis B virus. Therefore, careful attention should be given to the maintenance of intestinal microecology of patients which can provide a sound foundation for the treatment of chronic infection with the hepatitis B virus.

• gut microbiota
• hepatitis B virus
• immune response

• epigenetics
• immunity
• inflammation
• macrophage
• metabolism
• non-alcoholic steatohepatitis
• transcription

Heat stress affects the livestock industry, especially in poultry. Screening for metabolic changes after early and chronic heat exposure in poultry would be beneficial in resolving the production issues. In this study, we identified differentially expressed proteins that affected early heat exposure during chronic heat stress. Chronic heat stress affected 277 proteins, of which 95 differed in expression by early heat exposure. Differentially expressed proteins were related to actin metabolism and also involved in carbohydrate and carbon metabolism. According to our results, early heat exposed liver of broilers activates the different physiological mechanisms for protection from later heat stress.

The increasing trend of global warming has affected the livestock industry through the heat stress, especially in poultry. Therefore, a better understanding of the mechanisms of heat stress in poultry would be helpful for maintaining the poultry production. Three groups were designed to determine early heat stress effects during chronic heat stress: CC, raised at a comfortable temperature; CH, chronic heat exposure at 35 °C for 21–35 days continuously; and HH, early heat exposure at 40 °C for 24 h at 5 days old with 35 °C temperature for 21–35 days continuously. In this study, proteome analysis was carried out to identify differentially expressed proteins in the liver tissue of broilers under chronic and early heat exposure. There were eight differentially expressed proteins from early heat stress during chronic heat exposure, which were related to actin metabolism. According to KEGG (Kyoto encyclopedia of genes and genomes) analysis, the proteins involved in carbohydrate metabolism were expressed to promote the metabolism of carbohydrates under chronic heat stress. Early heat reduced the heat stress-induced expression changes of select proteins. Our study has shown that early heat exposure suggests that the liver of broilers has various physiological mechanisms for regulating homeostasis to aid heat resistance.

• broiler
• early heat exposure
• heat stress
• proteomics

• acute heat stress
• chicken
• heat shock protein
• small intestine

• aetiology
• cirrhosis
• disease severity
• inflammation
• malnutrition
• proton pump inhibitor

The incidence of ulcerative colitis (UC) is increasing worldwide, and it has become a growing problem in Asia. Previous research on UC has focused on serum, plasma, urine, gut tissues, and fecal metabolic profiling, but a comprehensive investigation into the correlation between the severity of colitis and changes in liver metabolism is still lacking. Since the liver and gut exchange nutrients and metabolites through a complex network, intestinal diseases can affect both the liver and other organs. In the present study, concentration-dependent dextran sodium sulfate (DSS)-induced ulcerative colitis was employed to examine changes in liver metabolism using a proton nuclear magnetic resonance spectroscopy (¹H-NMR)-and ultra-performance liquid chromatography time of flight mass spectroscopy (UPLC-TOF MS)-based metabolomics study. Using the multivariate statistical analysis method orthogonal projections to latent structures discriminant analysis (OPLS-DA), changes in metabolites depending on the DSS dose could be clearly distinguished. Specifically, hepatic metabolites involved in one-carbon metabolism, carnitine-related metabolism, and nucleotide synthesis were found to be affected by intestinal inflammation, implying the existence of a metabolic connection between the gut and liver. We are currently investigating the significance of this metabolic condition in UC.

• colitis
• gut and liver connection
• metabolomics

• bacterial overgrowth syndrome
• bile acids
• lipopolysaccharide
• non alcoholic fatty liver disease
• small intestine

Increasing evidence point to the relevance of intestinal disfunction and changes in the microbiome composition during chronic liver disease. More specifically, recent studies have highlighted that cholestatic diseases associate with a reduction in the microbiome diversity in patients. Still, the dynamics of the changes in the microbiome composition observed, as well as their implication in contributing to the pathogenesis of this disease remain largely undefined. Hence, experimental mouse models resembling the human pathogenesis are crucial to move forward our understanding on the mechanisms underpinning cholestatic disease and to enable the development of effective therapeutics. Our results show that the bile duct ligation (BDL) experimental model of cholestasis leads to rapid and significant changes in the microbiome diversity, with more than 100 OTUs being significantly different in faecal samples obtained from WT mice at 3 days and 7 days after BDL when compared to control animals. Changes in the microbial composition in mice after BDL included the enrichment of Akkermansia, Prevotella, Bacteroides and unclassified Ruminococcaceae in parallel with a drastic reduction of the presence of Faecalibacterium prausnitzii. In conclusion, our results support that bile duct ligation induces changes in the microbiome that partly resemble the gut microbial changes observed during human cholestatic disease.

The ecosystem of the gut microbiota consists of diverse intestinal species with multiple metabolic and immunologic activities and it is closely connected with the intestinal epithelia and mucosal immune response, with which it builds a complex barrier against intestinal pathogenic bacteria. The microbiota ensures the integrity of the gut barrier through multiple mechanisms, either by releasing antibacterial molecules (bacteriocins) and anti-inflammatory short-chain fatty acids or by activating essential cell receptors for the immune response. Experimental studies have confirmed the role of the intestinal microbiota in the epigenetic modulation of the gut barrier through posttranslational histone modifications and regulatory mechanisms induced by epithelial miRNA in the epithelial lumen. Any quantitative or functional changes of the intestinal microbiota, referred to as dysbiosis, alter the immune response, decrease epithelial permeability and destabilize intestinal homeostasis. Consequently, the overgrowth of pathobionts (Staphylococcus, Pseudomonas, and Escherichia coli) favors intestinal translocations with Gram negative bacteria or their endotoxins and could trigger sepsis, septic shock, secondary peritonitis, or various intestinal infections. Intestinal infections also induce epithelial lesions and perpetuate the risk of bacterial translocation and dysbiosis through epithelial ischemia and pro-inflammatory cytokines. Furthermore, the decline of protective anaerobic bacteria (Bifidobacterium and Lactobacillus) and inadequate release of immune modulators (such as butyrate) affects the release of antimicrobial peptides, de-represses microbial virulence factors and alters the innate immune response. As a result, intestinal germs modulate liver pathology and represent a common etiology of infections in HIV immunosuppressed patients. Antibiotic and antiretroviral treatments also promote intestinal dysbiosis, followed by the selection of resistant germs which could later become a source of infections. The current article addresses the strong correlations between the intestinal barrier and the microbiota and discusses the role of dysbiosis in destabilizing the intestinal barrier and promoting infectious diseases.

• HIV infection
• dysbiosis
• epigenetic modulation
• immunity
• intestinal microbiota
• liver infections
• sepsis
• short chain fatty acids

• chronic liver diseases
• dysbiosis degree
• gut microbiota
• primary hepatocellular carcinoma
• prognosis

• Ammonia
• Hepatic encephalopathy
• Liver cirrhosis
• Sarcopenia
• Testosterone

A growing number of investigations report the association between gut permeability and intestinal or extra-intestinal disorders under the basis that translocation of gut luminal contents could affect tissue function, either directly or indirectly. Still, in many cases it is unknown whether disruption of the gut barrier is a causative agent or a consequence of these conditions. Adequate experimental models are therefore required to further understand the pathophysiology of health disorders associated to gut barrier disruption and to develop and test pharmacological treatments. Here, we review the current animal models that display enhanced intestinal permeability, and discuss (1) their suitability to address mechanistic questions, such as the association between gut barrier alterations and disease and (2) their validity to test potential treatments for pathologies that are characterized by enhanced intestinal permeability.

• barrier
• epithelium
• gastrointestinal disorders
• gut
• permeability

• Gut-liver-Axis
• MCD
• NASH
• microbiota

• Animals
• Choline/adverse effects
• Choline/metabolism
• Choline Deficiency/metabolism
• Diet, High-Fat/adverse effects
• Disease Models, Animal
• Gastrointestinal Microbiome/drug effects
• Gastrointestinal Microbiome/genetics
• Genetic Variation/genetics
• Humans
• Inflammation/genetics
• Inflammation/metabolism
• Inflammation/microbiology
• Liver Cirrhosis/etiology
• Liver Cirrhosis/metabolism
• Liver Cirrhosis/pathology
• Male
• Methionine/adverse effects
• Methionine/deficiency
• Methionine/metabolism
• Mice
• Non-alcoholic Fatty Liver Disease/etiology
• Non-alcoholic Fatty Liver Disease/metabolism
• Non-alcoholic Fatty Liver Disease/pathology

• TR 285/10-1 Deutsche Forschungsgemeinschaft
• ObiHep grant #01KU1214A Bundesministerium für Bildung und Forschung
• LiSyM (CT) Bundesministerium für Bildung und Forschung
• HDHL-INTIMIC Di-Mi-Liv Bundesministerium für Bildung und Forschung

• Acidosis/complications
• Acute Disease
• Adult
• Aged
• Aged, 80 and over
• Ascitic Fluid
• Female
• Humans
• Intestinal Diseases/etiology
• Intestinal Diseases/pathology
• Intestinal Diseases/surgery
• Laparotomy/adverse effects
• Leukocytosis/complications
• Male
• Mesenteric Ischemia/complications
• Mesenteric Ischemia/diagnosis
• Mesenteric Ischemia/surgery
• Mesenteric Vascular Occlusion/complications
• Middle Aged
• Necrosis/etiology
• Peritonitis/complications
• Portal Vein/diagnostic imaging
• Retrospective Studies
• Tomography, X-Ray Computed
• Venous Thrombosis/complications
• Venous Thrombosis/diagnostic imaging

Gut microbial dysbiosis is correlated with the development of hepatocellular carcinoma (HCC). Therefore, analyzing the changing patterns in gut microbiota during HCC development, especially before HCC occurrence, is essential for the diagnosis and prevention of HCC based on gut microbial composition. However, these changing patterns in HCC are poorly understood, especially considering the sex differences in HCC incidence and mortality. Here, with an aim to determine the relationship between gut microbiota and HCC development in both sexes, and to screen potential microbial biomarkers for HCC diagnosis, we studied the changing patterns in the gut microbiota from mice of both sexes with liver-specific knockout of Tsc1 (LTsc1KO) that spontaneously developed HCC by 9–10 months of age and compared them to the patterns observed in their wide-type Tsc1^fl/fl cohorts using high-throughput sequencing. Using the LTsc1KO model, we were able to successfully exclude the continuing influence of diet on the gut microbiota. Based on gut microbial composition, the female LTsc1KO mice exhibited gut microbial disorder earlier than male LTsc1KO mice during the development of HCC. Our findings also indicated that the decrease in the relative abundance of anaerobic bacteria and the increase in the relative abundance of facultative anaerobic bacteria can be used as risk indexes of female HCC, but would be invalid for male HCC. Most of the changes in the gut bacteria were different between female and male LTsc1KO mice. In particular, the increased abundances of Allobaculum, Erysipelotrichaceae, Neisseriaceae, Sutterella, Burkholderiales, and Prevotella species have potential for use as risk indicators of female HCC, and the increased abundances of Paraprevotella, Paraprevotellaceae, and Prevotella can probably be applied as risk indicators of male HCC. These relationships between the gut microbiota and HCC discovered in the present study may serve as a platform for the identification of potential targets for the diagnosis and prevention of HCC in the future.

• Tsc1-knockout mice
• biomarker
• gut microbiota
• hepatocellular carcinoma
• sex-based response

The chronic infection of hepatitis B virus (HBV) is the most potent risk factor for the development of cirrhosis and hepatocellular carcinoma (HCC). The association of intestinal microbiota alteration with progressive liver disease has been investigated in recent studies. Overgrowth of potentially pathogenic bacteria of gram‐negative species and, in particular, a significant increase in the fecal count of Escherichia coli (E. coli) are characterized in the presence of HCC. This study was conducted to describe the characteristics of the intestinal microbiota related to the presence of HCC in HBV‐carrier patients. The available literature indicates the colonization of E. coli as principal source of portal vein lipopolysaccharide (LPS), in the gut may contribute to the carcinogenesis process by inducing chronic inflammation. This understanding could help to predict the clinical outcomes in HBV‐carrier patients and innovative strategies to reduce the virulence of liver disease from intestinal dysbiosis.

• Escherichia coli
• HBV-carrier patients
• hepatocellular carcinoma
• intestinal microbiota
• lipopolysaccharide

• Bacterial translocation
• Chronic liver disease
• Inflammation
• Intestinal permeability
• Pregnane X receptor
• Tight junctions

• 16S rRNA gene sequencing
• aromatic amino acids
• chronic hepatitis B
• gut sysbiosis
• serum metabolomics

• Bacterial translocation
• Bile composition
• Gut-derived factors
• Liver injury
• Self-filling blind loop
• Small-bowel bacterial overgrowth

Chronic high-salt diet-associated renal injury is a key risk factor for the development of hypertension. However, the mechanism by which salt triggers kidney damage is poorly understood. Our study investigated how high salt (HS) intake triggers early renal injury by considering the ‘gut-kidney axis’. We fed mice 2% NaCl in drinking water continuously for 8 weeks to induce early renal injury. We found that the ‘quantitative’ and ‘qualitative’ levels of the intestinal microflora were significantly altered after chronic HS feeding, which indicated the occurrence of enteric dysbiosis. In addition, intestinal immunological gene expression was impaired in mice with HS intake. Gut permeability elevation and enteric bacterial translocation into the kidney were detected after chronic HS feeding. Gut bacteria depletion by non-absorbable antibiotic administration restored HS loading-induced gut leakiness, renal injury and systolic blood pressure elevation. The fecal microbiota from mice fed chronic HS could independently cause gut leakiness and renal injury. Our current work provides a novel insight into the mechanism of HS-induced renal injury by investigating the role of the intestine with enteric bacteria and gut permeability and clearly illustrates that chronic HS loading elicited renal injury and dysfunction that was dependent on the intestine.

• diet
• gut
• heat-shock protein
• microbiota.

Even in cases where viral replication has been controlled by antiretroviral therapy for long periods of time, human immunodeficiency virus (HIV)-infected patients have several non-acquired immunodeficiency syndrome (AIDS) related co-morbidities, including liver disease, cardiovascular disease and neurocognitive decline, which have a clear impact on survival. It has been considered that persistent innate and acquired immune activation contributes to the pathogenesis of these non-AIDS related diseases. Immune activation has been related with several conditions, remarkably with the bacterial translocation related with the intestinal barrier damage by the HIV or by hepatitis C virus (HCV)-related liver cirrhosis. Consequently, increased morbidity and mortality must be expected in HIV-HCV coinfected patients. Disrupted gut barrier lead to an increased passage of microbial products and to an activation of the mucosal immune system and secretion of inflammatory mediators, which in turn might increase barrier dysfunction. In the present review, the intestinal barrier structure, measures of intestinal barrier dysfunction and the modifications of them in HIV monoinfection and in HIV-HCV coinfection will be considered. Both pathogenesis and the consequences for the progression of liver disease secondary to gut microbial fragment leakage and immune activation will be assessed.

• Human immunodeficiency virus infection
• Hepatitis C virus infection
• Innate immunity
• Acquired immunity
• Gut barrier

• Adaptive Immunity
• Animals
• Bacterial Translocation
• Coinfection
• Gastrointestinal Microbiome
• HIV/immunology
• HIV Infections/diagnosis
• HIV Infections/immunology
• HIV Infections/microbiology
• HIV Infections/virology
• Hepacivirus/immunology
• Hepatitis C/diagnosis
• Hepatitis C/immunology
• Hepatitis C/microbiology
• Hepatitis C/virology
• Host-Pathogen Interactions
• Humans
• Immunity, Innate
• Immunity, Mucosal
• Intestinal Mucosa/immunology
• Intestinal Mucosa/microbiology
• Intestinal Mucosa/virology
• Permeability
• Prognosis

• Animals
• Anti-Bacterial Agents/pharmacology
• Bacterial Translocation
• Blood Glucose/analysis
• CX3C Chemokine Receptor 1
• Homeostasis
• Immunity, Innate
• Intestinal Mucosa/metabolism
• Intestines/microbiology
• Macrophages/physiology
• Male
• Mice
• Mice, Inbred C57BL
• Microbiota
• Non-alcoholic Fatty Liver Disease/immunology
• Non-alcoholic Fatty Liver Disease/metabolism
• Receptors, Chemokine/physiology

• diagnosis
• epidemiology
• natural history
• non-alcoholic fatty liver disease
• pathogenesis
• treatment