Fungi participate in the dysbiosis of gut microbiota in patients with primary sclerosing cholangitis

Lemoinne, Sara; Kemgang, Astrid; Belkacem, Karima Ben; Straube, Marjolène; Jégou, Sarah; Corpechot, Christophe; Chazouillères, Olivier; Housset, Chantal; Sokol, Harry

doi:10.1136/gutjnl-2018-317791

Cited by 151 publications

(160 citation statements)

References 49 publications

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“…The study does not include a validation cohort similar to most of the other large microbiome studies in PSC, but still replicate several of the bacterial changes described above, and report an increase of the fungal Exophiala genus and Sordariomycetes class, and a depletion of the Saccharomycetaceae family, in addition to signs of disruptions in fungal‐bacterial networks in the gut microbiome of patients with PSC. In addition, IBD status in PSC does not seem to have an impact on the fungal composition …”

Section: Introductionmentioning

confidence: 93%

“…Importantly, bacteria are not the only microbes in the gut. Could fungi and bacterial‐fungal interactions be relevant, as observed in IBD? A very recent publication by Lemoinne et al is the first to explores this topic in PSC, and describe both bacterial and fungal changes in PSC patients compared to healthy controls . The study does not include a validation cohort similar to most of the other large microbiome studies in PSC, but still replicate several of the bacterial changes described above, and report an increase of the fungal Exophiala genus and Sordariomycetes class, and a depletion of the Saccharomycetaceae family, in addition to signs of disruptions in fungal‐bacterial networks in the gut microbiome of patients with PSC.…”

Section: Introductionmentioning

confidence: 99%

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The gut microbial influence on cholestatic liver disease

Kummen

Hov

2019

Liver International

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Patients with cholestatic liver diseases like primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC) have a different gut microbiome composition than healthy controls. In contrast with PBC, PSC has a strong association with inflammatory bowel disease and is the prototypical disease of the gut‐liver axis. Still, there are some distinct overlapping microbial features in the microbiome of patients with PSC and PBC suggesting similarities in cholestatic diseases, although the possible pathogenetic involvement of these shared microbial changes is unknown. Herein, we present an overview of the available data and discuss the relevance for potential disease relevant host‐microbiota interactions. In general, the microbiome interacts with the host via the immunobiome (interactions between the host immune system and the gut microbiome), the endobiome (where the gut microbiome contributes to host physiology by producing or metabolizing endogenous molecules) and the xenobiome (gut microbial transformation of exogenous compounds, including nutrients and drugs). Experimental and human observational evidence suggest that the presence and functions of gut microbes are relevant for the severity and progression of cholestatic liver disease. Interestingly, the majority of new drugs that are currently being tested in PBC and PSC in clinical trials act on bile acid homeostasis, where the endobiome is important. In the future, it will be paramount to perform longitudinal studies, through which we can identify new intervention targets, biomarkers or treatment‐stratifiers. In this way, gut microbiome‐based clinical care and therapy may become relevant in cholestatic liver disease within the foreseeable future.

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Section: Introductionmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 99%

The gut microbial influence on cholestatic liver disease

Kummen

Hov

2019

Liver International

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“…3 Emerging work demonstrates dietary exposure also shapes fungal communities. 8 However, despite evidence for fungal pattern recognition receptors in the human gut 6 and fungal influences on disease in the human gut, 31,32 continuous gut colonization by fungi remains controversial in humans. 33 Convincing evidence indicates fungi colonize the mouse gut and influence host physiology 34 and disease.…”

Section: Discussionmentioning

confidence: 99%

The gut mycobiome of healthy mice is shaped by the environment and shapes metabolic outcomes in response to diet

Mims

Abdullah

Stewart

et al. 2020

Preprint

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ABSTRACTObjectiveAs an active interface between the host and their diet, the gut bacteriome influences host metabolic adaptation. However, the contribution of gut fungi to host metabolic outcomes is not yet understood. Therefore, we aimed to determine if host metabolic response to an ultra-processed diet reflects gut fungal community composition.DesignWe compared jejunal fungi and bacteria from 72 healthy mice with the same genetic background but different starting mycobiomes before and after 8 weeks on an ultra-processed or standardized diet using 16S and internal transcribed spacer region 2 ribosomal RNA sequencing. We measured host body composition using magnetic resonance imaging, examined changes in metabolically active host tissues and quantified serum metabolic biomarkers.ResultsGut fungal communities are highly variable between mice, differing by vendor, age and sex. After exposure to an ultra-processed diet for 8 weeks, persistent differences in fungal community composition strongly associate with differential deposition of body mass in male mice compared to mice on standardized diet. Fat deposition in the liver, genomic adaptation of metabolically active tissues and serum metabolic biomarkers are correlated with alterations in fungal diversity and community composition. Variation in fungi from the genera Thermomyces and Saccharomyces most strongly associate with increased weight gain.ConclusionsIn the gut of healthy mice, host-microbe metabolic interactions strongly reflect variability in fungal communities. Our results confirm the importance of luminal fungal communities to host metabolic adaptation to dietary exposure. Gut fungal communities may represent a therapeutic target for the prevention and treatment of metabolic disease.Graphical AbstractIn BriefWhat is already known about this subject?Gut bacterial communities have evolved to influence the metabolic outcomes of the host in mammals. Evidence from across the lifespan suggests that differences in composition of these communities is associated with energy consumption. However, gut microbial communities, while often equated to bacteria, are diverse, multi-kingdom ecologies and limited information is available for the role of other kingdoms of life, such as fungi.What are the new findings?Gut fungal communities, collectively termed the mycobiome, are less diverse and abundant than bacterial communities in the gastrointestinal tract. This study identifies the considerable influence of the environment and dietary exposure on the composition of jejunal fungal communities in healthy mice with the same genetic background. After exposure to processed diet, differences in fungal community composition in male mice were strongly correlated with persistent differences body composition and markers of metabolic tone.How might it impact on clinical practice in the foreseeable future?These results verify that the baseline metabolic tone of health mice strongly reflects the ecological complexity of the gastrointestinal mycobiome. Variation in the composition of gut fungal communities is likely an underappreciated source of experimental and clinical variability in metabolic studies. Gastrointestinal fungi are likely a target for prevention and treatment of metabolic disease.

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“…Dysbiosis, i.e., the abnormal composition of gut microbiota, has been described in patients across several diseases, included cirrhosis (77), PBC (78), and PSC (79). Dysbiosis in the gut can also involve viral and fungal species, as recently proved in IBD (80) and PSC (81). Germ-free Mdr2-/-mice show increased hepatitis and cholestatic injury compared to conventionally-housed Mdr2-/mice (82).…”

Section: Modulation Of the Microbiota And Gut-liver Axismentioning

confidence: 95%

New Therapeutic Targets in Autoimmune Cholangiopathies

et al. 2020

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Primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) are autoimmune cholangiopathies characterized by limited treatment options. A more accurate understanding of the several pathways involved in these diseases has fostered the development of novel and promising targeted drugs. For PBC, the characterization of the role of farnesoid X receptor (FXR) and perixosome-proliferator activated receptor (PPAR) has paved the way to several clinical trials including different molecules with choleretic and antinflammatory action. Conversely, different pathogenetic models have been proposed in PSC such as the "leaky gut" hypothesis, a dysbiotic microbiota or a defect in mechanisms protecting against bile acid toxicity. Along these theories, new treatment approaches have been developed, ranging from drugs interfering with trafficking of lymphocytes from the gut to the liver, fecal microbiota transplantation or new biliary acids with possible immunomodulatory potential. Finally, for both diseases, antifibrotic agents are under investigation. In this review, we will illustrate current understanding of molecular mechanisms in PBC and PSC, focusing on actionable biological pathways for which novel treatments are being developed.

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Fungi participate in the dysbiosis of gut microbiota in patients with primary sclerosing cholangitis

Cited by 151 publications

References 49 publications

The gut microbial influence on cholestatic liver disease

The gut microbial influence on cholestatic liver disease

The gut mycobiome of healthy mice is shaped by the environment and shapes metabolic outcomes in response to diet

New Therapeutic Targets in Autoimmune Cholangiopathies

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