scholarly journals The Gut-Liver Axis in Health and Disease: The Role of Gut Microbiota-Derived Signals in Liver Injury and Regeneration

2021 ◽  
Vol 12 ◽  
Author(s):  
Zhipeng Zheng ◽  
Baohong Wang
Keyword(s):  
Liver Injury ◽  
Gut Microbiota ◽  
Liver Regeneration ◽  
Liver Diseases ◽  
Molecular Mechanisms ◽  
Short Chain Fatty Acids ◽  
Pathophysiological Process ◽  
Tryptophan Metabolites ◽  
Health And Disease

Diverse liver diseases undergo a similar pathophysiological process in which liver regeneration follows a liver injury. Given the important role of the gut-liver axis in health and diseases, the role of gut microbiota-derived signals in liver injury and regeneration has attracted much attention. It has been observed that the composition of gut microbiota dynamically changes in the process of liver regeneration after partial hepatectomy, and gut microbiota modulation by antibiotics or probiotics affects both liver injury and regeneration. Mechanically, through the portal vein, the liver is constantly exposed to gut microbial components and metabolites, which have immense effects on the immunity and metabolism of the host. Emerging data demonstrate that gut-derived lipopolysaccharide, gut microbiota-associated bile acids, and other bacterial metabolites, such as short-chain fatty acids and tryptophan metabolites, may play multifaceted roles in liver injury and regeneration. In this perspective, we provide an overview of the possible molecular mechanisms by which gut microbiota-derived signals modulate liver injury and regeneration, highlighting the potential roles of gut microbiota in the development of gut microbiota-based therapies to alleviate liver injury and promote liver regeneration.

scholarly journals The Controversial Role of Human Gut Lachnospiraceae

2020 ◽  
Vol 8 (4) ◽  
pp. 573 ◽  
Author(s):  
Mirco Vacca ◽  
Giuseppe Celano ◽  
Francesco Maria Calabrese ◽  
Piero Portincasa ◽  
Marco Gobbetti ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Gut Microbiota ◽  
Short Chain Fatty Acids ◽  
Intestinal Lumen ◽  
Human Gut ◽  
The Core ◽  
Host Diet ◽  
Health And Disease ◽  
Host Physiology

The complex polymicrobial composition of human gut microbiota plays a key role in health and disease. Lachnospiraceae belong to the core of gut microbiota, colonizing the intestinal lumen from birth and increasing, in terms of species richness and their relative abundances during the host’s life. Although, members of Lachnospiraceae are among the main producers of short-chain fatty acids, different taxa of Lachnospiraceae are also associated with different intra- and extraintestinal diseases. Their impact on the host physiology is often inconsistent across different studies. Here, we discuss changes in Lachnospiraceae abundances according to health and disease. With the aim of harnessing Lachnospiraceae to promote human health, we also analyze how nutrients from the host diet can influence their growth and how their metabolites can, in turn, influence host physiology.

scholarly journals Human Gut Microbiome and Liver Diseases: From Correlation to Causation

2021 ◽  
Vol 9 (5) ◽  
pp. 1017
Author(s):  
Rui Li ◽  
Zhengsheng Mao ◽  
Xujun Ye ◽  
Tao Zuo
Keyword(s):  
Liver Injury ◽  
Gut Microbiota ◽  
Gut Microbiome ◽  
Liver Diseases ◽  
Current Evidence ◽  
Human Gut ◽  
Multiple Organs ◽  
Traditional Function ◽  
High Throughput Dna Sequencing

The important role of human gut microbiota in liver diseases has long been recognized as dysbiosis and the translocation of certain microbes from the gut to liver. With the development of high-throughput DNA sequencing, the complexity and integrity of the gut microbiome in the whole spectrum of liver diseases is emerging. Specific patterns of gut microbiota have been identified in liver diseases with different causes, including alcoholic, non-alcoholic, and virus induced liver diseases, or even at different stages, ranging from steatohepatitis, fibrosis, cirrhosis, to hepatocellular carcinoma. At the same time, the mechanism of how microbiota contributes to liver diseases goes beyond the traditional function of the gut–liver axis which could lead to liver injury and inflammation. With the application of proteomics, metabolomics, and modern molecular technologies, more microbial metabolites and the complicated interaction of microbiota with host immunity come into our understanding in the liver pathogenesis. Germ-free animal models serve as a workhorse to test the function of microbiota and their derivatives in liver disease models. Here, we review the current evidence on the relationship between gut microbiota and liver diseases, and the mechanisms underlying this phenotype. In addition to original liver diseases, gut microbiota might also affect liver injury in systemic disorders involving multiple organs, as in the case of COVID-19 at a severe state. A better understanding of the gut microbial contribution to liver diseases might help us better benefit from this guest–host relationship and pave the way for novel therapies.

scholarly journals The Gut Microbiota: How Does It Influence the Development and Progression of Liver Diseases

Biomedicines ◽  
2020 ◽  
Vol 8 (11) ◽  
pp. 501
Author(s):  
Paulraj Kanmani ◽  
Kanmani Suganya ◽  
Hojun Kim
Keyword(s):  
Gut Microbiota ◽  
Liver Diseases ◽  
Intestinal Inflammation ◽  
Lipoteichoic Acid ◽  
Short Chain Fatty Acids ◽  
Bidirectional Relationship ◽  
Host Health ◽  
Cellular Components ◽  
Gut Microbiota Composition

The gut–liver axis plays important roles in both the maintenance of a healthy liver and the pathogenesis of liver diseases, where the gut microbiota acts as a major determinant of this relationship. Gut bacteria-derived metabolites and cellular components are key molecules that affect the function of the liver and modulate the pathology of liver diseases. Accumulating evidence showed that gut microbiota produces a myriad of molecules, including lipopolysaccharide, lipoteichoic acid, peptidoglycan, and DNA, as well as short-chain fatty acids, bile acids, trimethylamine, and indole derivatives. The translocation of these components to the liver exerts beneficial or pathogenic effects by interacting with liver immune cells. This is a bidirectional relationship. Therefore, the existence of crosstalk between the gut and liver and its implications on host health and diseases are essential for the etiology and treatment of diseases. Several mechanisms have been proposed for the pathogenesis of liver diseases, but still, the mechanisms behind the pathogenic role of gut-derived components on liver pathogenesis remain elusive and not understandable. This review discusses the current progress on the gut microbiota and its components in terms of the progression of liver diseases, and in turn, how liver diseases indirectly affect the intestinal function and induce intestinal inflammation. Moreover, this paper highlights the current therapeutic and preventive strategies used to restore the gut microbiota composition and improve host health.

scholarly journals Chicken-eaters and pork-eaters have different gut microbiota and tryptophan metabolites

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jie Shi ◽  
Di Zhao ◽  
Fan Zhao ◽  
Chong Wang ◽  
Galia Zamaratskaia ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Gut Microbiota ◽  
Short Chain Fatty Acids ◽  
Short Chain ◽  
Branched Chain Fatty Acids ◽  
Tryptophan Metabolites ◽  
Branched Chain ◽  
Spearman’S Correlation ◽  
Gut Microbiota Composition ◽  
Chain Fatty Acids

AbstractThis study was aimed to evaluate the differences in the composition of gut microbiota, tryptophan metabolites and short-chain fatty acids in feces between volunteers who frequently ate chicken and who frequently ate pork. Twenty male chicken-eaters and 20 male pork-eaters of 18 and 30 years old were recruited to collect feces samples for analyses of gut microbiota composition, short-chain fatty acids and tryptophan metabolites. Chicken-eaters had more diverse gut microbiota and higher abundance of Prevotella 9, Dialister, Faecalibacterium, Megamonas, and Prevotella 2. However, pork-eaters had higher relative abundance of Bacteroides, Faecalibacterium, Roseburia, Dialister, and Ruminococcus 2. In addition, chicken-eaters had high contents of skatole and indole in feces than pork-eaters, as well as higher contents of total short chain fatty acids, in particular for acetic acid, propionic acid, and branched chain fatty acids. The Spearman’s correlation analysis revealed that the abundance of Prevotella 2 and Prevotella 9 was positively correlated with levels of fecal skatole, indole and short-chain fatty acids. Thus, intake of chicken diet may increase the risk of skatole- and indole-induced diseases by altering gut microbiota.

scholarly journals The Role of the Gut Microbiome in Liver Cirrhosis Treatment

2020 ◽  
Vol 22 (1) ◽  
pp. 199
Author(s):  
Na Young Lee ◽  
Ki Tae Suk
Keyword(s):  
Liver Cirrhosis ◽  
Liver Disease ◽  
Liver Fibrosis ◽  
Gut Microbiota ◽  
Gut Microbiome ◽  
Liver Diseases ◽  
Sclerosing Cholangitis ◽  
Chronic Liver ◽  
Chronic Liver Diseases

Liver cirrhosis is one of the most prevalent chronic liver diseases worldwide. In addition to viral hepatitis, diseases such as steatohepatitis, autoimmune hepatitis, sclerosing cholangitis and Wilson’s disease can also lead to cirrhosis. Moreover, alcohol can cause cirrhosis on its own and exacerbate chronic liver disease of other causes. The treatment of cirrhosis can be divided into addressing the cause of cirrhosis and reversing liver fibrosis. To this date, there is still no clear consensus on the treatment of cirrhosis. Recently, there has been a lot of interest in potential treatments that modulate the gut microbiota and gut-liver axis for the treatment of cirrhosis. According to recent studies, modulation of the gut microbiome by probiotics ameliorates the progression of liver disease. The precise mechanism for relieving cirrhosis via gut microbial modulation has not been identified. This paper summarizes the role and effects of the gut microbiome in cirrhosis based on experimental and clinical studies on absorbable antibiotics, probiotics, prebiotics, and synbiotics. Moreover, it provides evidence of a relationship between the gut microbiome and liver fibrosis.

scholarly journals The roles and mechanisms of hypoxia in liver fibrosis

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Jingyao Cai ◽  
Min Hu ◽  
Zhiyang Chen ◽  
Zeng Ling
Keyword(s):  
Quality Of Life ◽  
Liver Fibrosis ◽  
Theoretical Basis ◽  
Liver Diseases ◽  
Molecular Mechanisms ◽  
Clinical Intervention ◽  
Chronic Liver Injury ◽  
Key Factor

AbstractLiver fibrosis occurs in response to any etiology of chronic liver injury. Lack of appropriate clinical intervention will lead to liver cirrhosis or hepatocellular carcinoma (HCC), seriously affecting the quality of life of patients, but the current clinical treatments of liver fibrosis have not been developed yet. Recent studies have shown that hypoxia is a key factor promoting the progression of liver fibrosis. Hypoxia can cause liver fibrosis. Liver fibrosis can, in turn, profoundly further deepen the degree of hypoxia. Therefore, exploring the role of hypoxia in liver fibrosis will help to further understand the process of liver fibrosis, and provide the theoretical basis for its diagnosis and treatment, which is of great significance to avoid further deterioration of liver diseases and protect the life and health of patients. This review highlights the recent advances in cellular and molecular mechanisms of hypoxia in developments of liver fibrosis.

Gab1 in livers with persistent hepatocyte apoptosis has an antiapoptotic effect and reduces chronic liver injury, fibrosis and tumorigenesis

2021 ◽  
Author(s):  
Tetsuo Takehara ◽  
Naoki Mizutani ◽  
Hayato Hikita ◽  
Yoshinobu Saito ◽  
Yuta Myojin ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Liver Injury ◽  
Cell Viability ◽  
Liver Regeneration ◽  
Adaptor Protein ◽  
Chronic Liver ◽  
Hepatocyte Apoptosis ◽  
Chronic Liver Injury ◽  
The Impact

Grb2-associated binder 1 (Gab1) is an adaptor protein that is important for intracellular signal transduction by receptor tyrosine kinases that are receptors for various growth factors and plays an important role in rapid liver regeneration after partial hepatectomy and during acute hepatitis. On the other hand, mild liver regeneration is induced in livers of individuals with chronic hepatitis, where hepatocyte apoptosis is persistent; however, the impact of Gab1 on such livers remains unclear. We examined the role of Gab1 in chronic hepatitis. Gab1 knockdown enhanced the decrease in cell viability and apoptosis induced by ABT-737, a Bcl-2/-xL/-w inhibitor, in BNL.CL2 cells, while cell viability and caspase activity were unchanged in the absence of ABT-737. ABT-737 treatment induced Gab1 cleavage to form p35-Gab1. p35-Gab1 was also detected in the livers of mice with hepatocyte-specific Mcl-1 knockout (KO), which causes persistent hepatocyte apoptosis. Gab1 deficiency exacerbated hepatocyte apoptosis in Mcl-1 KO mice with posttranscriptional downregulation of Bcl-XL. In BNL.CL2 cells treated with ABT-737, Gab1 knockdown posttranscriptionally suppressed Bcl-xL expression, and p35-Gab1 overexpression enhanced Bcl-xL expression. Gab1 deficiency in Mcl-1 KO mice activated STAT3 signaling in hepatocytes, increased hepatocyte proliferation, and increased the incidence of liver cancer with the exacerbation of liver fibrosis. In conclusion, Gab1 is cleaved in the presence of apoptotic stimuli and forms p35-Gab1 in hepatocytes. In chronic liver injury, the role of Gab1 in suppressing apoptosis and reducing liver damage, fibrosis, and tumorigenesis is more important than its role in liver regeneration.

scholarly journals Role of gut microbiota in liver diseases

2012 ◽  
Vol 43 (2) ◽  
pp. 139-146 ◽  
Author(s):  
Yasuhiro Miyake ◽  
Kazuhide Yamamoto
Keyword(s):  
Gut Microbiota ◽  
Liver Diseases
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