The gut mycobiome: a novel player in chronic liver diseases

Jiang, Lu; Stärkel, Peter; Fan, Jian‐Gao; Fouts, Derrick E.; Bächer, Petra; Schnabl, Bernd

doi:10.1007/s00535-020-01740-5

Cited by 26 publications

(30 citation statements)

References 121 publications

(160 reference statements)

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“…With the advent of deep sequencing technologies, the composition and diversity of the fungal microbiota has been revealed, deepening and clarifying our understanding of the roles and mechanisms of intestinal fungi in host homeostasis (Iliev and Leonardi, 2017;Scheffold et al, 2020;Zhang et al, 2020;Zou et al, 2020). Recent studies have unveiled the potential roles that fungi play in modulating host immune homeostasis and inflammatory disease (Standaert-Vitse et al, 2006;Wheeler et al, 2016;Sokol et al, 2017;Yang et al, 2017;Cirstea et al, 2020;Huang et al, 2020;Jiang et al, 2020). However, the fungal microbiota is still a novel and emerging topic of research that continues to lag behind the level of research and understanding we have of the bacteriome.…”

Section: Discussionmentioning

confidence: 99%

“…Fungi are suggested to influence intestinal health and disease by suppressing the outgrowth of potential pathobionts, promoting immunoregulatory pathways, and modulating host metabolism (Huseyin et al, 2017;Ni et al, 2017;Sam et al, 2017;Chin et al, 2020). Several clinical studies have identified a distinct fungal microbiota dysbiosis in inflammatory bowel disease (IBD), primary sclerosing cholangitis, asthma, type 2 diabetes mellitus, chronic liver diseases, Parkinson's disease and other neurological diseases, and even colorectal cancer (Hoarau et al, 2016;Sokol et al, 2017;Forbes et al, 2018;Coker et al, 2019;Cirstea et al, 2020;Jayasudha et al, 2020;Jiang et al, 2020;Lemoinne et al, 2020;Qiu et al, 2020;van Tilburg Bernardes et al, 2020;Ventin-Holmberg et al, 2020). Studies of animal models have found that commensal fungi can activate hostprotective immune pathways related to epithelial barrier integrity, but can also induce reactions that contribute to events associated with IBD (Iliev and Cadwell, 2020).…”

Section: Introductionmentioning

confidence: 99%

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Fecal Fungal Dysbiosis in Chinese Patients With Alzheimer’s Disease

Ling

Zhu

Liu

et al. 2021

Front. Cell Dev. Biol.

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Gut bacterial dysbiosis plays a vital role in the development of Alzheimer’s disease (AD). However, our understanding of alterations to the gut fungal microbiota and their correlations with host immunity in AD is still limited. Samples were obtained from 88 Chinese patients with AD, and 65 age- and gender-matched, cognitively normal controls. Using these samples, we investigated the fungal microbiota targeting internal transcribed spacer 2 (ITS2) rRNA genes using MiSeq sequencing, and analyzed their associations with the host immune response. Our data demonstrated unaltered fungal diversity but altered taxonomic composition of the fecal fungal microbiota in the AD patients. The analysis of the fungal microbiota was performed using 6,585,557 high-quality reads (2,932,482 reads from the controls and 3,653,075 from the AD patients), with an average of 43,042 reads per sample. We found that several key differential fungi such as Candida tropicalis and Schizophyllum commune were enriched in the AD patients, while Rhodotorula mucilaginosa decreased significantly. Interestingly, C. tropicalis and S. commune were positively correlated with IP-10 and TNF-α levels. In contrast, C. tropicalis was negatively correlated with IL-8 and IFN-γ levels, and R. mucilaginosa was negatively correlated with TNF-α level. PiCRUSt analysis revealed that lipoic acid metabolism, starch and sucrose metabolism were significantly decreased in the AD fungal microbiota. This study is the first to demonstrate fecal fungal dysbiosis in stable AD patients at a deeper level, and to identify the key differential fungi involved in regulating host systemic immunity. The analysis of the fungal microbiota in AD performed here may provide novel insights into the etiopathogenesis of AD and pave the way for improved diagnosis and treatment of AD.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Fecal Fungal Dysbiosis in Chinese Patients With Alzheimer’s Disease

Ling

Zhu

Liu

et al. 2021

Front. Cell Dev. Biol.

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“…Differences in DNA extraction methods, the lack of consensus primer pairs, diverging sequencing techniques, different software packages, and the lack of a complete database for taxonomic assignment make studies different to compare [232][233][234]. Fungi are said to play an important role in the homeostasis of the gut microbiome and in immunity [235,236]. In mice, the ability of Candida albicans substitution during antibiotic intake to promote bacterial recovery on the one hand, but to change the gut microbiome composition in the long term on the other hand was demonstrated [237].…”

Section: Gut Mycobiome 61 Introductionmentioning

confidence: 99%

“…Another example of the importance of fungi in keeping the gut healthy is that secretion of certain enzymes by Saccharomyces boulardii can neutralize toxins of Clostridioides difficile and Escherichia coli endotoxins in rats [239,240]. Same to bacteria, fungi also communicate with the immune system through PAMPs [235]. The key receptor to fungi is Dectin-1 (CLEC7A), which detects β-glucans found in the cell wall of fungi and protects against fungal infections [241,242].…”

Section: Gut Mycobiome 61 Introductionmentioning

confidence: 99%

“…For IBS, fungal dysbiosis was linked to increased intestinal hypersensitivity while the added value of the investigation of the mycobiome for diagnostic or therapeutic aims was doubted in one study [253,254]. Concerning liver diseases, changes of the mycobiome characterized by lower diversity and Candida overgrowth for ALD and by lower diversity and distinct fungal composition in NAFLD were demonstrated [235].…”

Section: Gut Mycobiome 61 Introductionmentioning

confidence: 99%

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The Gut-Liver Axis in Cholestatic Liver Diseases

Blesl

Stadlbauer

2021

Nutrients

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The gut-liver axis describes the physiological interplay between the gut and the liver and has important implications for the maintenance of health. Disruptions of this equilibrium are an important factor in the evolution and progression of many liver diseases. The composition of the gut microbiome, the gut barrier, bacterial translocation, and bile acid metabolism are the key features of this cycle. Chronic cholestatic liver diseases include primary sclerosing cholangitis, the generic term secondary sclerosing cholangitis implying the disease secondary sclerosing cholangitis in critically ill patients and primary biliary cirrhosis. Pathophysiology of these diseases is not fully understood but seems to be multifactorial. Knowledge about the alterations of the gut-liver axis influencing the pathogenesis and the outcome of these diseases has considerably increased. Therefore, this review aims to describe the function of the healthy gut-liver axis and to sum up the pathological changes in these cholestatic liver diseases. The review compromises the actual level of knowledge about the gut microbiome (including the mycobiome and the virome), the gut barrier and the consequences of increased gut permeability, the effects of bacterial translocation, and the influence of bile acid composition and pool size in chronic cholestatic liver diseases. Furthermore, therapeutic implications and future scientific objectives are outlined.

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Hepatic fibrosis 2022: Unmet needs and a blueprint for the future

2022

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Steady progress over four decades toward understanding the pathogenesis and clinical consequences of hepatic fibrosis has led to the expectation of effective antifibrotic drugs, yet none has been approved. Thus, an assessment of the field is timely, to clarify priorities and accelerate progress. Here, we highlight the successes to date but, more importantly, identify gaps and unmet needs, both experimentally and clinically. These include the need to better define cell-cell interactions and etiology-specific elements of fibrogenesis and their link to disease-specific drivers of portal hypertension. Success in treating viral hepatitis has revealed the remarkable capacity of the liver to degrade scar in reversing fibrosis, yet we know little of the mechanisms underlying this response. Thus, there is an exigent need to clarify the cellular and molecular mechanisms of fibrosis regression in order for therapeutics to mimic the liver's endogenous capacity. Better refined and more predictive in vitro and animal models will hasten drug development. From a clinical perspective, current diagnostics are improving but not always biologically plausible or sufficiently accurate to supplant biopsy. More urgently, digital pathology methods that leverage machine learning and artificial intelligence must be validated in order to capture more prognostic information from liver biopsies and better quantify the response to therapies. For more refined treatment of NASH, orthogonal approaches that integrate genetic, clinical, and pathological data sets may yield treatments for specific subphenotypes of the disease.Collectively, these and other advances will strengthen and streamline clinical trials and better link histologic responses to clinical outcomes.

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The gut mycobiome: a novel player in chronic liver diseases

Cited by 26 publications

References 121 publications

Fecal Fungal Dysbiosis in Chinese Patients With Alzheimer’s Disease

Fecal Fungal Dysbiosis in Chinese Patients With Alzheimer’s Disease

The Gut-Liver Axis in Cholestatic Liver Diseases

Hepatic fibrosis 2022: Unmet needs and a blueprint for the future

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