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Special Issue "Liver–Gut Axis"

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: 30 April 2021.

Special Issue Editor

Dr. Takemi Akahane
Website
Guest Editor
Department of Gastroenterology, Nara Medical University, Nara, Japan
Interests: leaky gut; endotoxin; nonalcoholic fatty liver disease; alcoholic liver disease; liver fibrosis; Toll-like receptors; probiotics; antibiotics

Special Issue Information

Dear Colleagues,

Gut-derived nutrients and other signals are delivered to the liver via the portal circulation. The liver as the largest immune organ hosts the entire spectrum of immune cell repertoire and has a remarkable capacity to recruit and activate immune cells in response to gut-derived metabolic or pathogen-derived signals. The crosstalk between the gut and liver is increasingly recognized, strengthened by the parallel rise in liver diseases and gastrointestinal and immune disorders. The gut–liver axis is widely implicated in the pathogenesis of liver disease, such as alcoholic liver disease, nonalcoholic fatty liver disease, primary biliary cholangitis, cirrhosis, hepatocellular carcinoma, and acute-on-chronic liver failure. The risk of damage to the liver increases when the intestinal barrier is damaged (“leaky gut”). Intestinal dysbiosis plays an important role in the development of chronic liver disease. The gut–liver axis has evolved from basic research to therapeutic strategies to improve the prognosis of chronic liver diseases. Further research on the gut–liver axis has led to new insights into the pathogenesis of liver disease and therapeutic strategies.

This Special Issue will be dedicated to “Liver–Gut Axis”; it welcomes submissions, including original papers and reviews, on these widely discussed topics.

Dr. Takemi Akahane
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Dysbiosis 
  • Leaky gut 
  • Gastrointestinal microbiome 
  • Endotoxin 
  • Antibiotics 
  • Probiotics 
  • Chronic liver disease 
  • Liver fibrosis 
  • Acute-on-chronic liver failure 
  • Hepatocellular carcinoma

Published Papers (4 papers)

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Research

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Open AccessArticle
Effective Combination Therapy of Angiotensin-II Receptor Blocker and Rifaximin for Hepatic Fibrosis in Rat Model of Nonalcoholic Steatohepatitis
Int. J. Mol. Sci. 2020, 21(15), 5589; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21155589 - 04 Aug 2020
Cited by 1
Abstract
The progression of nonalcoholic steatohepatitis (NASH) is complicated. The multiple parallel-hits theory is advocated, which includes adipocytokines, insulin resistance, endotoxins, and oxidative stress. Pathways involving the gut–liver axis also mediate the progression of NASH. Angiotensin-II receptor blockers (ARB) suppress hepatic fibrosis via the [...] Read more.
The progression of nonalcoholic steatohepatitis (NASH) is complicated. The multiple parallel-hits theory is advocated, which includes adipocytokines, insulin resistance, endotoxins, and oxidative stress. Pathways involving the gut–liver axis also mediate the progression of NASH. Angiotensin-II receptor blockers (ARB) suppress hepatic fibrosis via the activation of hepatic stellate cells (HSCs). Rifaximin, a nonabsorbable antibacterial agent, is used for the treatment of hepatic encephalopathy and has been recently reported to improve intestinal permeability. We examined the inhibitory effects on and mechanism of hepatic fibrogenesis by combining ARB and rifaximin administration. Fischer 344 rats were fed a choline-deficient/l-amino acid-defined (CDAA) diet for 8 weeks to generate the NASH model. The therapeutic effect of combining an ARB and rifaximin was evaluated along with hepatic fibrogenesis, the lipopolysaccharide–Toll-like receptor 4 (TLR4) regulatory cascade, and intestinal barrier function. ARBs had a potent inhibitory effect on hepatic fibrogenesis by suppressing HSC activation and hepatic expression of transforming growth factor-β and TLR4. Rifaximin reduced intestinal permeability by rescuing zonula occludens-1 (ZO-1) disruption induced by the CDAA diet and reduced portal endotoxin. Rifaximin directly affect to ZO-1 expression on intestinal epithelial cells. The combination of an ARB and rifaximin showed a stronger inhibitory effect compared to that conferred by a single agent. ARBs improve hepatic fibrosis by inhibiting HSCs, whereas rifaximin improves hepatic fibrosis by improving intestinal permeability through improving intestinal tight junction proteins (ZO-1). Therefore, the combination of ARBs and rifaximin may be a promising therapy for NASH fibrosis. Full article
(This article belongs to the Special Issue Liver–Gut Axis)
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Review

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Open AccessReview
Bile Acids and Microbiota: Multifaceted and Versatile Regulators of the Liver–Gut Axis
Int. J. Mol. Sci. 2021, 22(3), 1397; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22031397 - 30 Jan 2021
Abstract
After their synthesis from cholesterol in hepatic tissues, bile acids (BAs) are secreted into the intestinal lumen. Most BAs are subsequently re-absorbed in the terminal ileum and are transported back for recycling to the liver. Some of them, however, reach the colon and [...] Read more.
After their synthesis from cholesterol in hepatic tissues, bile acids (BAs) are secreted into the intestinal lumen. Most BAs are subsequently re-absorbed in the terminal ileum and are transported back for recycling to the liver. Some of them, however, reach the colon and change their physicochemical properties upon modification by gut bacteria, and vice versa, BAs also shape the composition and function of the intestinal microbiota. This mutual interplay of both BAs and gut microbiota regulates many physiological processes, including the lipid, carbohydrate and energy metabolism of the host. Emerging evidence also implies an important role of this enterohepatic BA circuit in shaping mucosal colonization resistance as well as local and distant immune responses, tissue physiology and carcinogenesis. Subsequently, disrupted interactions of gut bacteria and BAs are associated with many disorders as diverse as Clostridioides difficile or Salmonella Typhimurium infection, inflammatory bowel disease, type 1 diabetes, asthma, metabolic syndrome, obesity, Parkinson’s disease, schizophrenia and epilepsy. As we cannot address all of these interesting underlying pathophysiologic mechanisms here, we summarize the current knowledge about the physiologic and pathogenic interplay of local site microbiota and the enterohepatic BA metabolism using a few selected examples of liver and gut diseases. Full article
(This article belongs to the Special Issue Liver–Gut Axis)
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Open AccessReview
The Role of the Gut Microbiome in Liver Cirrhosis Treatment
Int. J. Mol. Sci. 2021, 22(1), 199; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22010199 - 28 Dec 2020
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Liver–Gut Axis)
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Open AccessReview
Liver Cirrhosis and Sarcopenia from the Viewpoint of Dysbiosis
Int. J. Mol. Sci. 2020, 21(15), 5254; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21155254 - 24 Jul 2020
Cited by 4
Abstract
Sarcopenia in patients with liver cirrhosis (LC) has been attracting much attention these days because of the close linkage to adverse outcomes. LC can be related to secondary sarcopenia due to protein metabolic disorders and energy metabolic disorders. LC is associated with profound [...] Read more.
Sarcopenia in patients with liver cirrhosis (LC) has been attracting much attention these days because of the close linkage to adverse outcomes. LC can be related to secondary sarcopenia due to protein metabolic disorders and energy metabolic disorders. LC is associated with profound alterations in gut microbiota and injuries at the different levels of defensive mechanisms of the intestinal barrier. Dysbiosis refers to a state in which the diversity of gut microbiota is decreased by decreasing the bacterial species and the number of bacteria that compose the gut microbiota. The severe disturbance of intestinal barrier in LC can result in dysbiosis, several bacterial infections, LC-related complications, and sarcopenia. Here in this review, we will summarize the current knowledge of the relationship between sarcopenia and dysbiosis in patients with LC. Full article
(This article belongs to the Special Issue Liver–Gut Axis)
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