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42 pages, 1278 KiB

Open AccessReview

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

by Hiroshi Fukui

Diseases 2019, 7(4), 58; https://doi.org/10.3390/diseases7040058 - 12 Nov 2019

Cited by 86 | Viewed by 14388

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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12 pages, 728 KiB

Open AccessReview

The Therapeutic Implications of the Gut Microbiome and Probiotics in Patients with NAFLD

by Brandon J. Perumpail, Andrew A. Li, Nimy John, Sandy Sallam, Neha D. Shah, Waiyee Kwong, George Cholankeril, Donghee Kim and Aijaz Ahmed

Diseases 2019, 7(1), 27; https://doi.org/10.3390/diseases7010027 - 25 Feb 2019

Cited by 37 | Viewed by 8604

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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22 pages, 680 KiB

Open AccessReview

Impact of Gut Dysbiosis on Neurohormonal Pathways in Chronic Kidney Disease

by Nima H. Jazani, Javad Savoj, Michael Lustgarten, Wei Ling Lau and Nosratola D. Vaziri

Diseases 2019, 7(1), 21; https://doi.org/10.3390/diseases7010021 - 13 Feb 2019

Cited by 51 | Viewed by 9670

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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10 pages, 398 KiB

Open AccessFeature PaperReview

Gut Microbiota, Fusobacteria, and Colorectal Cancer

by Dervla Kelly, Liying Yang and Zhiheng Pei

Diseases 2018, 6(4), 109; https://doi.org/10.3390/diseases6040109 - 11 Dec 2018

Cited by 79 | Viewed by 7983

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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13 pages, 422 KiB

Open AccessFeature PaperReview

Neuropsychiatric Disorders: Influence of Gut Microbe to Brain Signalling

by Mary Scriven, Timothy G. Dinan, John F. Cryan and Mary Wall

Diseases 2018, 6(3), 78; https://doi.org/10.3390/diseases6030078 - 6 Sep 2018

Cited by 33 | Viewed by 8500

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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10 pages, 236 KiB

Open AccessFeature PaperReview

Gut Microbiome and Cardiovascular Diseases

by Naofumi Yoshida, Tomoya Yamashita and Ken-ichi Hirata

Diseases 2018, 6(3), 56; https://doi.org/10.3390/diseases6030056 - 29 Jun 2018

Cited by 75 | Viewed by 8909

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)

9 pages, 239 KiB

Open AccessFeature PaperReview

Psoriasis and Microbiota: A Systematic Review

by Farida Benhadou, Dillon Mintoff, Benjamin Schnebert and Hok Bing Thio

Diseases 2018, 6(2), 47; https://doi.org/10.3390/diseases6020047 - 2 Jun 2018

Cited by 80 | Viewed by 12797

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)

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9 pages, 28444 KiB

Open AccessCommentary

The Brain–Intestinal Mucosa–Appendix– Microbiome–Brain Loop

by Luis Vitetta, Gemma Vitetta and Sean Hall

Diseases 2018, 6(2), 23; https://doi.org/10.3390/diseases6020023 - 1 Apr 2018

Cited by 10 | Viewed by 14581

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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