scholarly journals Role of Gut Dysbiosis in Liver Diseases: What Have We Learned So Far?

Diseases ◽  
2019 ◽  
Vol 7 (4) ◽  
pp. 58 ◽  
Author(s):  
Hiroshi Fukui
Keyword(s):  
Gut Microbiota ◽  
Fatty Liver ◽  
Liver Diseases ◽  
Pathogenic Bacteria ◽  
Inflammatory Responses ◽  
Early Death ◽  
Barrier Dysfunction ◽  
Nonalcoholic Fatty Liver ◽  
Gut Dysbiosis ◽  
Cirrhotic Patients

Accumulating evidence supports that gut dysbiosis may relate to various liver diseases. Alcoholics with high intestinal permeability had a decrease in the abundance of Ruminnococcus. Intestinal dysmotility, increased gastric pH, and altered immune responses in addition to environmental and genetic factors are likely to cause alcohol-associated gut microbial changes. Alcohol-induced dysbiosis may be associated with gut barrier dysfunction, as microbiota and their products modulate barrier function by affecting epithelial pro-inflammatory responses and mucosal repair functions. High levels of plasma endotoxin are detected in alcoholics, in moderate fatty liver to advanced cirrhosis. Decreased abundance of Faecalibacterium prausnitzii, an anti-inflammatory commensal, stimulating IL-10 secretion and inhibiting IL-12 and interferon-γ expression. Proteobacteria, Enterobacteriaceae, and Escherichia were reported to be increased in NAFLD (nonalcoholic fatty liver disease) patients. Increased abundance of fecal Escherichia to elevated blood alcohol levels in these patients and gut microbiota enriched in alcohol-producing bacteria produce more alcohol (alcohol hypothesis). Some undetermined pathological sequences related to gut dysbiosis may facilitate energy-producing and proinflammatory conditions for the progression of NAFLD. A shortage of autochthonous non-pathogenic bacteria and an overgrowth of potentially pathogenic bacteria are common findings in cirrhotic patients. The ratio of the amounts of beneficial autochthonous taxa (Lachnospiraceae + Ruminococaceae + Veillonellaceae + Clostridiales Incertae Sedis XIV) to those of potentially pathogenic taxa (Enterobacteriaceae + Bacteroidaceae) was low in those with early death and organ failure. Cirrhotic patients with decreased microbial diversity before liver transplantation were more likely to develop post-transplant infections and cognitive impairment related to residual dysbiosis. Patients with PSC had marked reduction of bacterial diversity. Enterococcus and Lactobacillus were increased in PSC patients (without liver cirrhosis.) Treatment-naive PBC patients were associated with altered composition and function of gut microbiota, as well as a lower level of diversity. As serum anti-gp210 antibody has been considered as an index of disease progression, relatively lower species richness and lower abundance of Faecalibacterium spp. in gp210-positive patients are interesting. The dysbiosis-induced altered bacterial metabolites such as a hepatocarcinogenesis promotor DCA, together with a leaky gut and bacterial translocation. Gut protective Akkermansia and butyrate-producing genera were decreased, while genera producing-lipopolysaccharide were increased in early hepatocellular carcinoma (HCC) patients.

scholarly journals Intestinal Permeability Is a Mechanical Rheostat in the Pathogenesis of Liver Cirrhosis

2021 ◽  
Vol 22 (13) ◽  
pp. 6921
Author(s):  
Norihisa Nishimura ◽  
Kosuke Kaji ◽  
Koh Kitagawa ◽  
Yasuhiko Sawada ◽  
Masanori Furukawa ◽  
...  
Keyword(s):  
Liver Disease ◽  
Gut Microbiota ◽  
Intestinal Permeability ◽  
Proinflammatory Cytokines ◽  
Liver Diseases ◽  
Pathogenic Bacteria ◽  
Necrosis Factor Alpha ◽  
Cytokines And Chemokines ◽  
Liver Disease Progression ◽  
Cirrhotic Patients

Recent studies have suggested that an alteration in the gut microbiota and their products, particularly endotoxins derived from Gram-negative bacteria, may play a major role in the pathogenesis of liver diseases. Gut dysbiosis caused by a high-fat diet and alcohol consumption induces increased intestinal permeability, which means higher translocation of bacteria and their products and components, including endotoxins, the so-called “leaky gut”. Clinical studies have found that plasma endotoxin levels are elevated in patients with chronic liver diseases, including alcoholic liver disease and nonalcoholic liver disease. A decrease in commensal nonpathogenic bacteria including Ruminococaceae and Lactobacillus and an overgrowth of pathogenic bacteria such as Bacteroidaceae and Enterobacteriaceae are observed in cirrhotic patients. The decreased diversity of the gut microbiota in cirrhotic patients before liver transplantation is also related to a higher incidence of post-transplant infections and cognitive impairment. The exposure to endotoxins activates macrophages via Toll-like receptor 4 (TLR4), leading to a greater production of proinflammatory cytokines and chemokines including tumor necrosis factor-alpha, interleukin (IL)-6, and IL-8, which play key roles in the progression of liver diseases. TLR4 is a major receptor activated by the binding of endotoxins in macrophages, and its downstream signal induces proinflammatory cytokines. The expression of TLR4 is also observed in nonimmune cells in the liver, such as hepatic stellate cells, which play a crucial role in the progression of liver fibrosis that develops into hepatocarcinogenesis, suggesting the importance of the interaction between endotoxemia and TLR4 signaling as a target for preventing liver disease progression. In this review, we summarize the findings for the role of gut-derived endotoxemia underlying the progression of liver pathogenesis.

Gut microbiota in nonalcoholic fatty liver diseases with and without type-2 diabetes mellitus

2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Hamed Ebrahimzadeh Leylabadlo ◽  
Hossein Samadi Kafil ◽  
Safar Farajnia ◽  
Dariush Shanehbandi ◽  
Seyed Yaghoub Moaddab ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Gut Microbiota ◽  
Fatty Liver ◽  
Liver Diseases ◽  
Nonalcoholic Fatty Liver ◽  
Nonalcoholic Fatty Liver Diseases

The Human Gut Microbiome in Liver Diseases

2017 ◽  
Vol 37 (02) ◽  
pp. 128-140 ◽  
Author(s):  
Brian Davis ◽  
Jasmohan Bajaj
Keyword(s):  
Liver Disease ◽  
Gut Microbiota ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Primary Sclerosing Cholangitis ◽  
Alcoholic Liver Disease ◽  
Fatty Liver Disease ◽  
Liver Diseases ◽  
Sclerosing Cholangitis ◽  
Nonalcoholic Fatty Liver

AbstractRecent advances in culture-independent laboratory techniques and bioinformatics have contributed to enriched characterizations of the gut microbiota and microbiome in chronic liver diseases such as alcoholic liver disease, nonalcoholic fatty liver disease, primary sclerosing cholangitis, primary biliary cholangitis, and cirrhosis. In this review, the authors focus on studies characterizing and modulating the gut microbiota and microbiome in humans. The majority of studies that characterized microbiota involved a small number of patients using 16S ribosomal RNA genetic sequencing. Few studies applied whole-genome shotgun sequencing and metagenomics analyses. The majority of clinical trials on modulating the microbiome have focused on probiotics or antibiotics in small groups of patients with cirrhosis versus healthy controls. Several trials are underway using fecal microbial transplantation in alcoholic liver disease, nonalcoholic fatty liver disease, primary sclerosing cholangitis, and cirrhosis. Future research is needed on understanding the viral and fungal microbiome and developing user-friendly microbiome tools.

scholarly journals The severity of nonalcoholic fatty liver disease is associated with gut dysbiosis and shift in the metabolic function of the gut microbiota

Hepatology ◽  
2016 ◽  
Vol 63 (3) ◽  
pp. 764-775 ◽  
Author(s):  
Jérôme Boursier ◽  
Olaf Mueller ◽  
Matthieu Barret ◽  
Mariana Machado ◽  
Lionel Fizanne ◽  
...  
Keyword(s):  
Liver Disease ◽  
Gut Microbiota ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Metabolic Function ◽  
Nonalcoholic Fatty Liver ◽  
Gut Dysbiosis

scholarly journals Oral Pathobiont-Induced Changes in Gut Microbiota Aggravate the Pathology of Nonalcoholic Fatty Liver Disease in Mice

2021 ◽  
Vol 12 ◽  
Author(s):  
Kyoko Yamazaki ◽  
Tamotsu Kato ◽  
Yuuri Tsuboi ◽  
Eiji Miyauchi ◽  
Wataru Suda ◽  
...  
Keyword(s):  
Gene Expression ◽  
Liver Disease ◽  
Gut Microbiota ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Expression Profiles ◽  
Nonalcoholic Fatty Liver ◽  
Gut Dysbiosis ◽  
Bacterial Products

Background & AimsPeriodontitis increases the risk of nonalcoholic fatty liver disease (NAFLD); however, the underlying mechanisms are unclear. Here, we show that gut dysbiosis induced by oral administration of Porphyromonas gingivalis, a representative periodontopathic bacterium, is involved in the aggravation of NAFLD pathology.MethodsC57BL/6N mice were administered either vehicle, P. gingivalis, or Prevotella intermedia, another periodontopathic bacterium with weaker periodontal pathogenicity, followed by feeding on a choline-deficient, l-amino acid-defined, high-fat diet with 60 kcal% fat and 0.1% methionine (CDAHFD60). The gut microbial communities were analyzed by pyrosequencing the 16S ribosomal RNA genes. Metagenomic analysis was used to determine the relative abundance of the Kyoto Encyclopedia of Genes and Genomes pathways encoded in the gut microbiota. Serum metabolites were analyzed using nuclear magnetic resonance-based metabolomics coupled with multivariate statistical analyses. Hepatic gene expression profiles were analyzed via DNA microarray and quantitative polymerase chain reaction.ResultsCDAHFD60 feeding induced hepatic steatosis, and in combination with bacterial administration, it further aggravated NAFLD pathology, thereby increasing fibrosis. Gene expression analysis of liver samples revealed that genes involved in NAFLD pathology were perturbed, and the two bacteria induced distinct expression profiles. This might be due to quantitative and qualitative differences in the influx of bacterial products in the gut because the serum endotoxin levels, compositions of the gut microbiota, and serum metabolite profiles induced by the ingested P. intermedia and P. gingivalis were different.ConclusionsSwallowed periodontopathic bacteria aggravate NAFLD pathology, likely due to dysregulation of gene expression by inducing gut dysbiosis and subsequent influx of gut bacteria and/or bacterial products.

scholarly journals Crosstalk between Gut and Brain in Alzheimer’s Disease: The Role of Gut Microbiota Modulation Strategies

Nutrients ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 690
Author(s):  
Umair Shabbir ◽  
Muhammad Sajid Arshad ◽  
Aysha Sameen ◽  
Deog-Hwan Oh
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Gut Microbiota ◽  
Dietary Habits ◽  
Inflammatory Responses ◽  
Fecal Microbiota Transplantation ◽  
Fecal Microbiota ◽  
Gut Dysbiosis ◽  
Dynamic Population

The gut microbiota (GM) represents a diverse and dynamic population of microorganisms and about 100 trillion symbiotic microbial cells that dwell in the gastrointestinal tract. Studies suggest that the GM can influence the health of the host, and several factors can modify the GM composition, such as diet, drug intake, lifestyle, and geographical locations. Gut dysbiosis can affect brain immune homeostasis through the microbiota–gut–brain axis and can play a key role in the pathogenesis of neurodegenerative diseases, including dementia and Alzheimer’s disease (AD). The relationship between gut dysbiosis and AD is still elusive, but emerging evidence suggests that it can enhance the secretion of lipopolysaccharides and amyloids that may disturb intestinal permeability and the blood–brain barrier. In addition, it can promote the hallmarks of AD, such as oxidative stress, neuroinflammation, amyloid-beta formation, insulin resistance, and ultimately the causation of neural death. Poor dietary habits and aging, along with inflammatory responses due to dysbiosis, may contribute to the pathogenesis of AD. Thus, GM modulation through diet, probiotics, or fecal microbiota transplantation could represent potential therapeutics in AD. In this review, we discuss the role of GM dysbiosis in AD and potential therapeutic strategies to modulate GM in AD.

scholarly journals Green Tea and Epigallocatechin Gallate (EGCG) for the Management of Nonalcoholic Fatty Liver Diseases (NAFLD): Insights into the Role of Oxidative Stress and Antioxidant Mechanism

Antioxidants ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1076
Author(s):  
Guoyi Tang ◽  
Yu Xu ◽  
Cheng Zhang ◽  
Ning Wang ◽  
Huabin Li ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Fatty Liver ◽  
Green Tea ◽  
Liver Diseases ◽  
Randomized Clinical Trials ◽  
Epigallocatechin Gallate ◽  
Protective Effects ◽  
Nonalcoholic Fatty Liver ◽  
Nonalcoholic Fatty Liver Diseases ◽  
Underlying Mechanisms

Nonalcoholic fatty liver diseases (NAFLD) represent a set of liver disorders progressing from steatosis to steatohepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma, which induce huge burden to human health. Many pathophysiological factors are considered to influence NAFLD in a parallel pattern, involving insulin resistance, oxidative stress, lipotoxicity, mitochondrial dysfunction, endoplasmic reticulum stress, inflammatory cascades, fibrogenic reaction, etc. However, the underlying mechanisms, including those that induce NAFLD development, have not been fully understood. Specifically, oxidative stress, mainly mediated by excessive accumulation of reactive oxygen species, has participated in the multiple NAFLD-related signaling by serving as an accelerator. Ameliorating oxidative stress and maintaining redox homeostasis may be a promising approach for the management of NAFLD. Green tea is one of the most important dietary resources of natural antioxidants, above which epigallocatechin gallate (EGCG) notably contributes to its antioxidative action. Accumulative evidence from randomized clinical trials, systematic reviews, and meta-analysis has revealed the beneficial functions of green tea and EGCG in preventing and managing NAFLD, with acceptable safety in the patients. Abundant animal and cellular studies have demonstrated that green tea and EGCG may protect against NAFLD initiation and development by alleviating oxidative stress and the related metabolism dysfunction, inflammation, fibrosis, and tumorigenesis. The targeted signaling pathways may include, but are not limited to, NRF2, AMPK, SIRT1, NF-κB, TLR4/MYD88, TGF-β/SMAD, and PI3K/Akt/FoxO1, etc. In this review, we thoroughly discuss the oxidative stress-related mechanisms involved in NAFLD development, as well as summarize the protective effects and underlying mechanisms of green tea and EGCG against NAFLD.

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