Special Issue "Gut Microbiome and Human Diseases"

A special issue of Diseases (ISSN 2079-9721).

Deadline for manuscript submissions: closed (31 December 2018).

Special Issue Editors

Prof. Dr. Hiroshi Fukui
Website
Guest Editor
Department of Gastroenterology, Endocrinology and Metabolism, Nara Medical University, Nara, Japan
Interests: gut microbiome; liver disease; metagenomics; metabolomics; alcoholic liver disease; nonalcoholic steatohepatitis(NASH); liver cirrhosis and hepatocellular carcinoma
Special Issues and Collections in MDPI journals
Prof. Dr. Luis Vitetta

Guest Editor
Sydney Medical School, The University of Sydney, Sydney, Australia
Medlab Clinical Ltd, Sydney, Australia
Interests: Intestinal microbiome, probiotics, immune function, Metabolic Disorders, Mood Disorders, Cancer
Ms. Emma Tali Saltzman

Guest Editor
Department of Pharmacology, School of Medicine, University of Sydney, Australia
The Boden Institute of Obesity, Nutrition, Exercise and Eating Disorders, School of Medicine, University of Sydney, Australia
Medlab Clinical Ltd, Sydney, Australia
Interests: Gut Microbiome, Non-alcoholic fatty liver disease, Metabolic Syndrome

Special Issue Information

Dear Colleagues,

The gut microbiome is the most densely populated microbial site on or within the human body. With at least 1000 different species of microbes residing in the human gastrointestinal tract (GIT), host-microbial crosstalk contributes to the maintenance of a homeostatic relationship between the two parties. The gut microbiome exerts immunological, protective and metabolic effects on the host, with a disruption to the balanced relationship posited to be involved in the pathogenesis of various diseases including liver, intestinal, metabolic, mental and immunological disorders. Intestinal epithelial cell dysbiosis linked to adverse shifts in the intestinal microbiome and their products is characterised by increased intestinal permeability and enhanced microbial translocation. Animal and human studies have confirmed the role of intestinal epithelial cell dysbiosis in the manifestation of metabolic syndrome and associated complications, including non-alcoholic fatty liver disease (NAFLD). The posited mechanism of action is that microbial translocation due to increased intestinal permeability can induce a state of metabolic endotoxemia when bacteria and bacterial fragments leak into systemic circulation and cultivate a pro-inflammatory environment in various organs. Low-grade chronic systemic inflammation not only provokes immunological disturbances but also contributes to the development of insulin resistance, type 2 diabetes mellitus and other obesity-related complications. Gut microbiome has further substantial impacts on cancer development.

This special issue, titled ‘Gut Microbiome and Human Diseases’, will aim to explore the current understanding of the role of the gut microbiome in the pathogenesis of liver, intestine, metabolic, mental and immunological disorders as well as research exploring how the gut microbiome can be manipulated with probiotics/prebiotics and antibiotics designated as adjunct medicines could beneficially help to treat these variable human diseases.

Prof. Dr. Hiroshi Fukui
Prof. Dr. Luis Vitetta
Ms. Emma Tali Saltzman
Guest Editors

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. Diseases is an international peer-reviewed open access quarterly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1000 CHF (Swiss Francs). 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

  • gut microbiome
  • liver diseases
  • non-alcoholic fatty liver disease (NAFLD)
  • type 2 Diabetes Mellitus (T2DM)
  • metabolic Syndrome (MetS)
  • probiotics
  • prebiotics
  • synbiotics
  • inflammatory bowel disease
  • irritable bowel syndrome
  • depression
  • allergic diseases
  • autoimmune diseases
  • cardiovascular diseases
  • renal diseases
  • cancer

Published Papers (8 papers)

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Review

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Open AccessReview
Role of Gut Dysbiosis in Liver Diseases: What Have We Learned So Far?
Diseases 2019, 7(4), 58; https://doi.org/10.3390/diseases7040058 - 12 Nov 2019
Cited by 5
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Gut Microbiome and Human Diseases)
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Open AccessReview
The Therapeutic Implications of the Gut Microbiome and Probiotics in Patients with NAFLD
Diseases 2019, 7(1), 27; https://doi.org/10.3390/diseases7010027 - 25 Feb 2019
Cited by 6
Abstract
Recent breakthrough in our understanding pertaining to the pathogenesis of nonalcoholic fatty liver disease (NAFLD) has pointed to dysregulation or derangement of the gut microbiome, also known as dysbiosis. This has led to growing interest in probiotic supplementation as a potential treatment method [...] Read more.
Recent breakthrough in our understanding pertaining to the pathogenesis of nonalcoholic fatty liver disease (NAFLD) has pointed to dysregulation or derangement of the gut microbiome, also known as dysbiosis. This has led to growing interest in probiotic supplementation as a potential treatment method for NAFLD due to its ability to retard and/or reverse dysbiosis and restore normal gut flora. A thorough review of medical literature was completed from inception through July 10, 2018 on the PubMed database by searching for key terms such as NAFLD, probiotics, dysbiosis, synbiotics, and nonalcoholic steatohepatitis (NASH). All studies reviewed indicate that probiotics had a beneficial effect in patients with NAFLD and its subset NASH. Results varied between studies, but there was evidence demonstrating improvement in liver enzymes, hepatic inflammation, hepatic steatosis, and hepatic fibrosis. No major adverse effects were noted. Currently, there are no guidelines addressing the use of probiotics in the setting of NAFLD. In conclusion, probiotics appear to be a promising option in the treatment of NAFLD. Future research is necessary to assess the efficacy of probiotics in patients with NAFLD. Full article
(This article belongs to the Special Issue Gut Microbiome and Human Diseases)
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Open AccessReview
Impact of Gut Dysbiosis on Neurohormonal Pathways in Chronic Kidney Disease
Diseases 2019, 7(1), 21; https://doi.org/10.3390/diseases7010021 - 13 Feb 2019
Cited by 13
Abstract
Chronic kidney disease (CKD) is a worldwide major health problem. Traditional risk factors for CKD are hypertension, obesity, and diabetes mellitus. Recent studies have identified gut dysbiosis as a novel risk factor for the progression CKD and its complications. Dysbiosis can worsen systemic [...] Read more.
Chronic kidney disease (CKD) is a worldwide major health problem. Traditional risk factors for CKD are hypertension, obesity, and diabetes mellitus. Recent studies have identified gut dysbiosis as a novel risk factor for the progression CKD and its complications. Dysbiosis can worsen systemic inflammation, which plays an important role in the progression of CKD and its complications such as cardiovascular diseases. In this review, we discuss the beneficial effects of the normal gut microbiota, and then elaborate on how alterations in the biochemical environment of the gastrointestinal tract in CKD can affect gut microbiota. External factors such as dietary restrictions, medications, and dialysis further promote dysbiosis. We discuss the impact of an altered gut microbiota on neuroendocrine pathways such as the hypothalamus–pituitary–adrenal axis, the production of neurotransmitters and neuroactive compounds, tryptophan metabolism, and the cholinergic anti-inflammatory pathway. Finally, therapeutic strategies including diet modification, intestinal alpha-glucosidase inhibitors, prebiotics, probiotics and synbiotics are reviewed. Full article
(This article belongs to the Special Issue Gut Microbiome and Human Diseases)
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Open AccessFeature PaperReview
Gut Microbiota, Fusobacteria, and Colorectal Cancer
Diseases 2018, 6(4), 109; https://doi.org/10.3390/diseases6040109 - 11 Dec 2018
Cited by 16
Abstract
The gut microbiota has emerged as an environmental contributor to colorectal cancer (CRC) in both animal models and human studies. It is now generally accepted that bacteria are ubiquitous colonizers of all exposed human body surfaces, including the entire alimentary tract (5). Recently, [...] Read more.
The gut microbiota has emerged as an environmental contributor to colorectal cancer (CRC) in both animal models and human studies. It is now generally accepted that bacteria are ubiquitous colonizers of all exposed human body surfaces, including the entire alimentary tract (5). Recently, the concept that a normal bacterial microbiota is essential for the development of inflammation-induced carcinoma has emerged from studies of well-known colonic bacterial microbiota. This review explores the evidence for a role of fusobacteria, an anaerobic gram-negative bacterium that has repeatedly been detected at colorectal tumor sites in higher abundance than surrounding histologically normal tissue. Mechanistic studies provide insight on the interplay between fusobacteria, other gut microbiota, barrier functions, and host responses. Studies have shown that fusobacteria activate host inflammatory responses designed to protect against pathogens that promote tumor growth. We discuss how future research identifying the pathophysiology underlying fusobacteria colon colonization during colorectal cancer may lead to new therapeutic targets for cancer. Furthermore, disease-protective strategies suppressing tumor development by targeting the local tumor environment via bacteria represent another exciting avenue for researchers and are highlighted in this review. Full article
(This article belongs to the Special Issue Gut Microbiome and Human Diseases)
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Open AccessFeature PaperReview
Neuropsychiatric Disorders: Influence of Gut Microbe to Brain Signalling
Diseases 2018, 6(3), 78; https://doi.org/10.3390/diseases6030078 - 06 Sep 2018
Cited by 11
Abstract
The microbiome gut brain (MGB) axis consists of bidirectional routes of communication between the gut and the brain. It has emerged as a potential therapeutic target for multiple medical specialties including psychiatry. Significant numbers of preclinical trials have taken place with some transitioning [...] Read more.
The microbiome gut brain (MGB) axis consists of bidirectional routes of communication between the gut and the brain. It has emerged as a potential therapeutic target for multiple medical specialties including psychiatry. Significant numbers of preclinical trials have taken place with some transitioning to clinical studies in more recent years. Some positive results have been reported secondary to probiotic administration in both healthy populations and specific patient groups. This review aims to summarise the current understanding of the MGB axis and the preclinical and clinical findings relevant to psychiatry. Significant differences have been identified between the microbiome of patients with a diagnosis of depressive disorder and healthy controls. Similar findings have occurred in patients diagnosed with bipolar affective disorder and irritable bowel syndrome. A probiotic containing Lactobacillus acidophilus, Lactobacillus casei, and Bifidobacterium bifidum produced a clinically measurable symptom improvement in patients with depressive disorder. To date, some promising results have suggested that probiotics could play a role in the treatment of stress-related psychiatric disease. However, more well-controlled clinical trials are required to determine which clinical conditions are likely to benefit most significantly from this novel approach. Full article
(This article belongs to the Special Issue Gut Microbiome and Human Diseases)
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Open AccessFeature PaperReview
Gut Microbiome and Cardiovascular Diseases
Diseases 2018, 6(3), 56; https://doi.org/10.3390/diseases6030056 - 29 Jun 2018
Cited by 20
Abstract
Recent evidence has suggested that the gut microbiome is involved in human health and diseases, such as inflammatory bowel disease, liver cirrhosis, rheumatoid arthritis, and type 2 diabetes. Cardiovascular diseases, which are associated with high morbidity and mortality across the world, are no [...] Read more.
Recent evidence has suggested that the gut microbiome is involved in human health and diseases, such as inflammatory bowel disease, liver cirrhosis, rheumatoid arthritis, and type 2 diabetes. Cardiovascular diseases, which are associated with high morbidity and mortality across the world, are no exception. Increasing evidence has suggested a strong relationship between the gut microbiome and the progression of cardiovascular diseases. We first reported such a relationship with coronary artery disease two years ago. Next-generation sequencing techniques, together with bioinformatics technology, constantly and dramatically expand our knowledge of the complex human gut bacterial ecosystem and reveal the exact role of this bacterial ecosystem in cardiovascular diseases via the functional analysis of the gut microbiome. Such knowledge may pave the way for the development of further diagnostics and therapeutics for prevention and management of cardiovascular diseases. The aim of the current review is to highlight the relationship between the gut microbiome and their metabolites, and the development of cardiovascular diseases by fostering an understanding of recent studies. Full article
(This article belongs to the Special Issue Gut Microbiome and Human Diseases)
Open AccessFeature PaperReview
Psoriasis and Microbiota: A Systematic Review
Diseases 2018, 6(2), 47; https://doi.org/10.3390/diseases6020047 - 02 Jun 2018
Cited by 22
Abstract
Background: Recent advances have highlighted the crucial role of microbiota in the pathophysiology of chronic inflammatory diseases as well as its impact on the efficacy of therapeutic agents. Psoriasis is a chronic, multifactorial inflammatory skin disorder, which has a microbiota distinct from healthy, [...] Read more.
Background: Recent advances have highlighted the crucial role of microbiota in the pathophysiology of chronic inflammatory diseases as well as its impact on the efficacy of therapeutic agents. Psoriasis is a chronic, multifactorial inflammatory skin disorder, which has a microbiota distinct from healthy, unaffected skin. Aim: Through an extensive review of the literature, we aim to discuss the skin and gut microbiota and redefine their role in the pathogenesis of psoriasis. Conclusions: Unfortunately, the direct link between the skin microbiota and the pathogenesis of psoriasis remains to be clearly established. Apart from improving the course of psoriasis, selective modulation of the microbiota may increase the efficacy of medical treatments as well as attenuate their side effects. Full article
(This article belongs to the Special Issue Gut Microbiome and Human Diseases)

Other

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Open AccessCommentary
The Brain–Intestinal Mucosa–Appendix– Microbiome–Brain Loop
Diseases 2018, 6(2), 23; https://doi.org/10.3390/diseases6020023 - 01 Apr 2018
Cited by 5
Abstract
The brain and the gut are connected from early fetal life. The mother’s exposure to microbial molecules is thought to exert in utero developmental effects on the fetus. These effects could importantly underpin the groundwork for subsequent pathophysiological mechanisms for achieving immunological tolerance [...] Read more.
The brain and the gut are connected from early fetal life. The mother’s exposure to microbial molecules is thought to exert in utero developmental effects on the fetus. These effects could importantly underpin the groundwork for subsequent pathophysiological mechanisms for achieving immunological tolerance and metabolic equilibrium post birth, events that continue through to 3–4 years of age. Furthermore, it is understood that the microbiome promotes cues that instruct the neonate’s mucosal tissues and skin in the language of molecular and cellular biology. Post birth mucosal lymphoid tissue formation and maturation (most probably including the vermiform appendix) is microbiota-encouraged co-establishing the intestinal microbiome with a developing immune system. Intestinal mucosal tissue maturation loops the brain-gut-brain and is postulated to influence mood dispositions via shifts in the intestinal microbiome phyla. A plausible appreciation is that dysregulated pro-inflammatory signals from intestinal resident macrophages could breach the loop by providing adverse mood signals via vagus nerve afferents to the brain. In this commentary, we further suggest that the intestinal resident macrophages act as an upstream traffic controller of translocated microbes and metabolites in order to maintain local neuro-endocrine-immunological equilibrium. When macrophages are overwhelmed through intestinal microbiome and intestinal epithelial cell dysbiosis, pro-inflammatory signals are sustained, which may then lead to mood disorders. The administration of probiotics as an adjunctive medicine co-administered with antidepressant medications in improving depressed mood may have biological and clinical standing. Full article
(This article belongs to the Special Issue Gut Microbiome and Human Diseases)
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