scholarly journals The role of bacterial metabolites derived from aromatic amino acids in non-alcoholic fatty liver disease

2020 ◽  
Vol 48 (6) ◽  
pp. 375-386
Author(s):  
E. S. Shcherbakova ◽  
T. S. Sall ◽  
S. I. Sitkin ◽  
T. Ya. Vakhitov ◽  
E. V. Demyanova
Keyword(s):  
Amino Acids ◽  
Liver Disease ◽  
Gut Microbiota ◽  
Fatty Liver Disease ◽  
Liver Steatosis ◽  
Aromatic Amino Acids ◽  
Microbial Metabolites ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

The review deals with the role of aromatic amino acids and their microbial metabolites in the development and progression of non-alcoholic fatty liver disease (NAFLD). Pathological changes typical for NAFLD, as well as abnormal composition and/or functional activity of gut microbiota, results in abnormal aromatic amino acid metabolism. The authors discuss the potential of these amino acids and their bacterial metabolites to produce both negative and positive impact on the main steps of NAFLD pathophysiology, such as lipogenesis and inflammation, as well as on the liver functions through regulation of the intestinal barrier and microbiota-gut-liver axis signaling. The review gives detailed description of the mechanism of biological activity of tryptophan and its derivatives (indole, tryptamine, indole-lactic, indole-propyonic, indole-acetic acids, and indole-3-aldehyde) through the activation of aryl hydrocarbon receptor (AhR), preventing the development of liver steatosis. Bacteria-produced phenyl-alanine metabolites could promote liver steatosis (phenyl acetic and phenyl lactic acids) or, on the contrary, could reduce liver inflammation and increase insulin sensitivity (phenyl propionic acid). Tyramine, para-cumarate, 4-hydroxyphenylacetic acids, being by-products of bacterial catabolism of tyrosine, can prevent NAFLD, whereas para-cresol and phenol accelerate the progression of NAFLD by damaging the barrier properties of intestinal epithelium. Abnormalities in bacterial catabolism of tyrosine, leading to its excess, stimulate fatty acid synthesis and promote lipid infiltration of the liver. The authors emphasize a close interplay between bacterial metabolism of aromatic amino acids by gut microbiota and the functioning of the human body. They hypothesize that microbial metabolites of aromatic amino acids may represent not only therapeutic targets or non-invasive biomarkers, but also serve as bioactive agents for NAFLD treatment and prevention.

scholarly journals Understanding the Role of the Gut Microbiome and Microbial Metabolites in Non-Alcoholic Fatty Liver Disease: Current Evidence and Perspectives

Biomolecules ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 56
Author(s):  
Natalia Vallianou ◽  
Gerasimos Socrates Christodoulatos ◽  
Irene Karampela ◽  
Dimitrios Tsilingiris ◽  
Faidon Magkos ◽  
...  
Keyword(s):  
Liver Disease ◽  
Gut Microbiota ◽  
Fatty Liver ◽  
Gut Microbiome ◽  
Fatty Liver Disease ◽  
Microbial Metabolites ◽  
Alcoholic Fatty Liver ◽  
Gut Dysbiosis ◽  
Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide. NAFLD begins as a relatively benign hepatic steatosis which can evolve to non-alcoholic steatohepatitis (NASH); the risk of cirrhosis and hepatocellular carcinoma (HCC) increases when fibrosis is present. NAFLD represents a complex process implicating numerous factors—genetic, metabolic, and dietary—intertwined in a multi-hit etiopathogenetic model. Recent data have highlighted the role of gut dysbiosis, which may render the bowel more permeable, leading to increased free fatty acid absorption, bacterial migration, and a parallel release of toxic bacterial products, lipopolysaccharide (LPS), and proinflammatory cytokines that initiate and sustain inflammation. Although gut dysbiosis is present in each disease stage, there is currently no single microbial signature to distinguish or predict which patients will evolve from NAFLD to NASH and HCC. Using 16S rRNA sequencing, the majority of patients with NAFLD/NASH exhibit increased numbers of Bacteroidetes and differences in the presence of Firmicutes, resulting in a decreased F/B ratio in most studies. They also present an increased proportion of species belonging to Clostridium, Anaerobacter, Streptococcus, Escherichia, and Lactobacillus, whereas Oscillibacter, Flavonifaractor, Odoribacter, and Alistipes spp. are less prominent. In comparison to healthy controls, patients with NASH show a higher abundance of Proteobacteria, Enterobacteriaceae, and Escherichia spp., while Faecalibacterium prausnitzii and Akkermansia muciniphila are diminished. Children with NAFLD/NASH have a decreased proportion of Oscillospira spp. accompanied by an elevated proportion of Dorea, Blautia, Prevotella copri, and Ruminococcus spp. Gut microbiota composition may vary between population groups and different stages of NAFLD, making any conclusive or causative claims about gut microbiota profiles in NAFLD patients challenging. Moreover, various metabolites may be involved in the pathogenesis of NAFLD, such as short-chain fatty acids, lipopolysaccharide, bile acids, choline and trimethylamine-N-oxide, and ammonia. In this review, we summarize the role of the gut microbiome and metabolites in NAFLD pathogenesis, and we discuss potential preventive and therapeutic interventions related to the gut microbiome, such as the administration of probiotics, prebiotics, synbiotics, antibiotics, and bacteriophages, as well as the contribution of bariatric surgery and fecal microbiota transplantation in the therapeutic armamentarium against NAFLD. Larger and longer-term prospective studies, including well-defined cohorts as well as a multi-omics approach, are required to better identify the associations between the gut microbiome, microbial metabolites, and NAFLD occurrence and progression.

Non-alcoholic fatty liver disease: An update with special focus on the role of gut microbiota

Metabolism ◽  
2017 ◽  
Vol 71 ◽  
pp. 182-197 ◽  
Author(s):  
Michael Doulberis ◽  
Georgios Kotronis ◽  
Dimitra Gialamprinou ◽  
Jannis Kountouras ◽  
Panagiotis Katsinelos
Keyword(s):  
Liver Disease ◽  
Gut Microbiota ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Special Focus ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

1052 D-Amino Acids as a Novel Link between Gut Microbiota and Non-Alcoholic Fatty Liver Disease

2016 ◽  
Vol 150 (4) ◽  
pp. S1056
Author(s):  
Wensheng Liu ◽  
Susan S. Baker ◽  
Ricardo A. Arbizu ◽  
Aswad Jackson ◽  
Robert D. Baker ◽  
...  
Keyword(s):  
Amino Acids ◽  
Liver Disease ◽  
Gut Microbiota ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

scholarly journals Gut Microbiota in Liver Disease: What Do We Know and What Do We Not Know?

Physiology ◽  
2020 ◽  
Vol 35 (4) ◽  
pp. 261-274 ◽  
Author(s):  
Lu Jiang ◽  
Bernd Schnabl
Keyword(s):  
Liver Disease ◽  
Gut Microbiota ◽  
Fatty Liver Disease ◽  
Liver Diseases ◽  
Chronic Liver Diseases ◽  
Alcoholic Fatty Liver ◽  
Bidirectional Communication ◽  
Microbial Products ◽  
Alcoholic Fatty Liver Disease

The gut and the liver have a bidirectional communication via the biliary system and the portal vein. The intestinal microbiota and microbial products play an important role for modulating liver diseases such as alcohol-associated liver disease, non-alcoholic fatty liver disease and steatohepatitis, and cholestatic liver diseases. Here, we review the role of the gut microbiota and its products for the pathogenesis and therapy of chronic liver diseases.

scholarly journals The role of gut microbiota in non-alcoholic fatty liver disease: pathways of mechanisms

2019 ◽  
Vol 38 (3) ◽  
pp. 81-88 ◽  
Author(s):  
Chyntia Olivia Maurine JASIRWAN ◽  
Cosmas Rinaldi Adithya LESMANA ◽  
Irsan HASAN ◽  
Andri Sanityosos SULAIMAN ◽  
Rino Alvani GANI
Keyword(s):  
Liver Disease ◽  
Gut Microbiota ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease ◽  
Disease Pathways
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