How does the microbiome affect liver disease?

Tilg, Herbert; Grander, Christoph; Moschen, Alexander R.

doi:10.1002/cld.586

Cited by 6 publications

(6 citation statements)

References 12 publications

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“…Dysbiosis of the intestinal microbiome is a known feature of alcohol-induced cirrhosis. Bifidobacteria, Streptococci, Veillonella and Enterobacteria were found to be elevated in cirrhosis, whereas Faecalibacterium showed a reduction [ 58 , 76 , 78 ]. In our cohort, we could observe reduced diversity, and on a genus level, also increased abundance of Veillonella compared to healthy controls.…”

Section: Discussionmentioning

confidence: 99%

Secondary Sclerosing Cholangitis in Critically Ill Patients Alters the Gut–Liver Axis: A Case Control Study

et al. 2020

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Secondary sclerosing cholangitis in critically ill patients (SC-CIP) occurs after long-term intensive care treatment. This study aimed to assess the gut–liver axis in SC-CIP. Stool microbiome composition, gut permeability, bacterial translocation and serum bile acid profiles of 18 SC-CIP patients compared to 11 patients after critical illness without liver disease (CIP controls), 21 patients with cirrhosis and 21 healthy controls were studied. 16S rDNA was isolated from stool and sequenced using the Illumina technique. Diamine oxidase, zonulin, soluble CD14 (sCD14) and lipopolysaccharide binding protein were measured in serum and calprotectin in stool. Serum bile acids were analyzed by high-performance liquid chromatography-mass spectrometry (HPLC-MS). Reduced microbiome alpha diversity and altered beta diversity were seen in SC-CIP, CIP controls and cirrhosis compared to healthy controls. SC-CIP patients showed a shift towards pathogenic taxa and an oralization. SC-CIP, CIP controls and cirrhotic patients presented with impaired gut permeability, and biomarkers of bacterial translocation were increased in SC-CIP and cirrhosis. Total serum bile acids were elevated in SC-CIP and cirrhosis and the bile acid profile was altered in SC-CIP, CIP controls and cirrhosis. In conclusions, observed alterations of the gut–liver axis in SC-CIP cannot solely be attributed to liver disease, but may also be secondary to long-term intensive care treatment.

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Section: Discussionmentioning

confidence: 99%

Secondary Sclerosing Cholangitis in Critically Ill Patients Alters the Gut–Liver Axis: A Case Control Study

et al. 2020

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“…Previous reports have shown that microbiota is changed in liver disease 28 and associated pathologies such as non-alcoholic fatty liver disease (NAFLD), cirrhosis 28 , type 2 diabetes and obesity 29, 30 . Different studies reported associations between Verrucomicrobia and liver related diseases.…”

Section: Discussionmentioning

confidence: 99%

Trem-2 modulation of gut microbiota is blunted during hepatotoxic injury and uncoupled from liver repair responses

Coelho

Duarte

Macedo

et al. 2019

Preprint

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49The involvement of gut microbiota in liver disease has been addressed in the 50 context of the "leaky gut hypothesis" postulating that dysbiosis allow microbial 51 components to elicit liver inflammatory responses and hepatic tissue damage. 52 Conversely, commensal gut microbiota acting on innate immune receptors 53 protect against hepatotoxic insults. Given that mice deficient for the triggering 54 receptor expressed on myeloid cells-2 (Trem-2) show increased vulnerability to 55 experimental drug-induced hepatic damage we explored the possibility that 56 Trem-2 is a modulator of gut microbiota composition. 57We found that microbiota composition in untreated Trem-2 KO mice differs from 58 the wild-type showing overall decrease in microbiota diversity and increased 59 representation of Verrucomicrobia. Interestingly, induction of liver damage with 60 hepatotoxic drugs blunted this microbiota diversity difference and altered phyla 61 composition with increased representation of Verrucomicrobia during acute 62 hepatic injury and Proteobacteria during chronic challenge. Furthermore, co-63 housing experiments that homogenized microbiota diversity showed that the 64 increased liver tissue vulnerability to hepatotoxic insults in Trem-2 KO mice was 65 not dependent on microbiota composition. This work uncouples Trem-2 66 dependent alterations in gut commensal microbiota from Trem-2 pro-recovery 67 effects in the damaged liver tissue. These findings support the possibility that 68 unlinked actions of innate immune receptors contribute to disease association 69 with microbiota alterations, particularly with the Verrucomicrobia phylum.70 4 Importance 71Trem-2 is a mammalian innate immunity receptor involved in development and 72 resolution of tissue damage, namely in the brain and in the liver. Nevertheless, 73 it is not known whether gut microbiota is contributing to these Trem-2 mediated 74 phenotypes. We found that Trem-2 KO mice spontaneously display different gut 75 microbiota composition as compared to wild-type mice, namely with increased 76 abundance of the phylum Verrucomicrobia. Notably these differences do not 77 impact the control of Trem-2 on liver tissue vulnerability to hepatotoxic insults. 78 This work uncouples Trem-2 modulation of gut microbiota and the role of Trem-79 2 on responses to liver damage. This work brings new insights on role of innate 80 immune receptors on the association of organic and systemic diseases with gut 81 microbiota. 82 83 84 85 Susceptibility to inflammatory disease often depends on the interplay of host 87 genetic factors with both immune system activation and microbiota 88 composition 1 . Clinical evidence and experimental models have shown that 89 disruption of gut homeostasis leads to leakage of bacterial products that reach 90 the liver fueling pro-inflammatory responses 2 . Yet, it is still unknown how 91 dysbiosis causes liver disease beyond increasing intestine permeability. The 92 unexpected increased vulnerability of germ-free mice to hepatotoxic treatments 3 93 rai...

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“…Compositional shifts in the gut microbiota are linked with liver disease 1 , 2 . In liver cirrhosis (LC), the alteration in gut microbiota is characterized by an overgrowth of potentially pathogenic bacteria and a decrease in beneficial commensal species 3 .…”

Section: Introductionmentioning

confidence: 99%

Combining amplicon sequencing and metabolomics in cirrhotic patients highlights distinctive microbiota features involved in bacterial translocation, systemic inflammation and hepatic encephalopathy

Iebba

Guerrieri

Gregorio

et al. 2018

Sci Rep

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In liver cirrhosis (LC), impaired intestinal functions lead to dysbiosis and possible bacterial translocation (BT). Bacteria or their byproducts within the bloodstream can thus play a role in systemic inflammation and hepatic encephalopathy (HE). We combined 16S sequencing, NMR metabolomics and network analysis to describe the interrelationships of members of the microbiota in LC biopsies, faeces, peripheral/portal blood and faecal metabolites with clinical parameters. LC faeces and biopsies showed marked dysbiosis with a heightened proportion of Enterobacteriaceae. Our approach showed impaired faecal bacterial metabolism of short-chain fatty acids (SCFAs) and carbon/methane sources in LC, along with an enhanced stress-related response. Sixteen species, mainly belonging to the Proteobacteria phylum, were shared between LC peripheral and portal blood and were functionally linked to iron metabolism. Faecal Enterobacteriaceae and trimethylamine were positively correlated with blood proinflammatory cytokines, while Ruminococcaceae and SCFAs played a protective role. Within the peripheral blood and faeces, certain species (Stenotrophomonas pavanii, Methylobacterium extorquens) and metabolites (methanol, threonine) were positively related to HE. Cirrhotic patients thus harbour a ‘functional dysbiosis’ in the faeces and peripheral/portal blood, with specific keystone species and metabolites related to clinical markers of systemic inflammation and HE.

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How does the microbiome affect liver disease?

Abstract: http://aasldpubs.onlinelibrary.wiley.com/hub/journal/10.1002/(ISSN)2046-2484/video/8-5-reading-tilg.html a video presentation of this article

Cited by 6 publications

References 12 publications

Secondary Sclerosing Cholangitis in Critically Ill Patients Alters the Gut–Liver Axis: A Case Control Study

Secondary Sclerosing Cholangitis in Critically Ill Patients Alters the Gut–Liver Axis: A Case Control Study

Trem-2 modulation of gut microbiota is blunted during hepatotoxic injury and uncoupled from liver repair responses

Combining amplicon sequencing and metabolomics in cirrhotic patients highlights distinctive microbiota features involved in bacterial translocation, systemic inflammation and hepatic encephalopathy

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