Bacteriophage targeting of gut bacterium attenuates alcoholic liver disease

Duan, Yi; Llorente, Cristina; Lang, Sonja; Brandl, Katharina; Chu, Huikuan; Jiang, Lu; White, Richard C.; Clarke, Thomas H.; Nguyen, Kevin; Torralba, Manolito; Shao, Yan; Liu, Jinyuan; Hernandez-Morales, Adriana; Lessor, Lauren; Rahman, Imran R; Miyamoto, Yukiko; Ly, Melissa; Gao, Bei; Sun, Weizhong; Kiesel, Roman; Hutmacher, Felix; Lee, Suhan; Ventura‐Cots, Meritxell; Bosques-Padilla, Francisco; Verna, Elizabeth C.; Abraldes, Juan G.; Brown, Robert S.; Vargas, Vı́ctor; Altamirano, José; Caballería, Juan; Shawcross, Debbie L.; Ho, Samuel B.; Louvet, Alexandre; Lucey, Michael R.; Maury, Philippe; García–Tsao, Guadalupe; Bataller, Ramón; Tu, Xin; Eckmann, Lars; Donk, Wilfred A. van der; Young, Ry; Lawley, Trevor D.; Stärkel, Peter; Pride, David T.; Fouts, Derrick E.; Schnabl, Bernd

doi:10.1038/s41586-019-1742-x

Cited by 601 publications

(587 citation statements)

References 62 publications

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“…itive E faecalis or associations of cytolysin-positivity and worse outcome in NAFLD patients. This is in contrast to what we observed in alcoholic hepatitis patients were cytolysin-positivity was detected in one third of the patients and strongly associated with mortality 2. In our previous study, we investigated mechanisms of how cytolysin might cause liver damage.…”

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confidence: 79%

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Cytolysin‐positive Enterococcus faecalis is not increased in patients with non‐alcoholic steatohepatitis

Lang

Demir

Duan

et al. 2020

Liver International

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Several studies show associations between gut bacterial dysbiosis and chronic liver diseases, but causative mechanisms are largely unclear. We recently identified cytolysin, a bacterial exotoxin expressed and secreted by Enterococcus faecalis to cause liver damage in the setting of alcohol‐related liver disease. Cytolysin was increased and highly correlated with liver disease severity and mortality in alcoholic hepatitis patients. In this study, we investigated if faecal cytolysin‐positivity can be linked to non‐alcoholic fatty liver disease, a highly prevalent disease where new biomarkers and treatment targets are urgently needed. In contrast to what we observed in alcoholic hepatitis, only seven out of 96 non‐alcoholic fatty liver disease patients were cytolysin‐positive, and these patients did not have increased liver disease activity compared with cytolysin‐negative patients. These results indicate that the association of cytolysin carriage with worse clinical outcome might be specific for alcoholic hepatitis.

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confidence: 79%

“…5 Realtime quantitative PCR for E faecalis and cytolysin was done as in our recent publication. 2 Only cylLL and cylLS genes were used.…”

Section: Bacterial Dna Extraction and Real-time Quantitative Pcrmentioning

confidence: 99%

Cytolysin‐positive Enterococcus faecalis is not increased in patients with non‐alcoholic steatohepatitis

Lang

Demir

Duan

et al. 2020

Liver International

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“…Dietary interventions, food compounds that can modify the GM (prebiotics) [59, 63] or metabolites generated from gut bacteria (postbiotics) [64, 65] might be beneficial. Engineering approaches like bacteriophages [66–68] specifically modifying gut bacteria are also suggested. These extensive findings will pave the way to translate GM use for clinical intervention, and more studies are imperative to evaluate its clinical value in the context of AF.…”

Section: Discussionmentioning

confidence: 99%

Shifts in gut microbiome and metabolome are associated with risk of recurrent atrial fibrillation

Zuo

Zhang

et al. 2020

Preprint

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Specific alterations of gut microbiota (GM) in atrial fibrillation (AF) patients, including elevated microbial diversity, particularly perturbed composition, imbalanced microbial function, and associated metabolic pattern modifications have been described in our previous report. The current work aimed to assess the association of GM composition with AF recurrence (RAF) after ablation, and to construct a GM-based predictive model for RAF. Gut microbial composition and metabolic profiles were assessed based on metagenomic sequencing and metabolomic analyses. Compared with non-AF controls (50 individuals), GM composition and metabolomic profile were significantly altered between patients with recurrent AF (17 individuals) and the non-RAF group (23 individuals). Notably, discriminative taxa between the non-RAF and RAF groups, including the families Nitrosomonadaceae and Lentisphaeraceae, the genera Marinitoga and Rufibacter, and the species Faecalibacterium sp. CAG:82, Bacillus gobiensis, and Desulfobacterales bacterium PC51MH44, were selected to construct a taxonomic scoring system based on LASSO analysis. An elevated area under curve (0.954) and positive net reclassification index (1.5601) for predicting RAF compared with traditional clinical scoring (AUC=0.6918) were obtained. The GM-based taxonomic scoring system theoretically improves the model performance. These data provide novel evidence that supports incorporating the GM factor into future recurrent risk stratification.

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“…The suggestions of Veillonella and Klebsiella pneumonia involving in PSC pathogenesis seem convincing [37,40,127], however the chicken-and-the-egg problem remains open, as both microbes seem to be involved in other liver and non-liver diseases and may also appear abundant due to the presence of advanced liver disease. The concept however is interesting, as it opens for the targeting of specific bacteria, as successfully done in murine experiments by specific bacteriophage killing in alcoholic hepatitis and PSC [130,148]. As our understanding of the gut microbiota in human diseases evolves, we are likely to see more specific therapeutic approaches along this thinking, targeting specific bacteria or specific pathways of gut microbial physiology.…”

Section: Probiotics and Bacteriophage Applicationsmentioning

confidence: 99%

Emerging therapies in primary sclerosing cholangitis: pathophysiological basis and clinical opportunities

Vesterhus

Karlsen

2020

J Gastroenterol

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Bacteriophage targeting of gut bacterium attenuates alcoholic liver disease

Abstract: Chronic liver disease due to alcohol use disorder contributes markedly to the global burden of disease and mortality 1-3. Alcoholic hepatitis is a severe and life-threatening form of alcohol-Duan et al.

Cited by 601 publications

References 62 publications

Cytolysin‐positive Enterococcus faecalis is not increased in patients with non‐alcoholic steatohepatitis

Cytolysin‐positive Enterococcus faecalis is not increased in patients with non‐alcoholic steatohepatitis

Shifts in gut microbiome and metabolome are associated with risk of recurrent atrial fibrillation

Emerging therapies in primary sclerosing cholangitis: pathophysiological basis and clinical opportunities

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