A Universal Gut-Microbiome-Derived Signature Predicts Cirrhosis

Oh, Tae Gyu; Kim, Susy M.; Caussy, Cyrielle; Fu, Ting; Guo, Jian; Bassirian, Shirin; Singh, Seema; Madamba, Egbert; Bettencourt, Ricki; Richards, Lisa; Yu, Ruth T.; Atkins, Annette R.; Huan, Tao; Brenner, David A.; Sirlin, Claude B.; Downes, Michael; Evans, Ronald M.; Loomba, Rohit

doi:10.1016/j.cmet.2020.06.005

Cited by 222 publications

(162 citation statements)

References 45 publications

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“…Currently, machine learning such as random forest analysis is increasingly used in the medical diagnostics field. 27,28 Using this strategy, here we found that separate microbial or metabolic markers could effectively discriminate the GDM individuals from HCs. Moreover, a combinatorial marker panel could distinguish GDM individuals from HCs with a positive predictive value of 82.6%, and a negative predictive value of 94.7%.…”

Section: Discussionmentioning

confidence: 88%

Altered gut bacterial and metabolic signatures and their interaction in gestational diabetes mellitus

Wang

Liu

et al. 2020

Gut Microbes

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Emerging evidence indicates that the gut microbiome can modulate metabolic homeostasis, and thus may influence the development of gestational diabetes mellitus (GDM). However, whether and how the gut microbiome and its correlated metabolites change in GDM is uncertain. Herein we compare the gut microbial compositions, and fecal and urine metabolomes, of 59 patients with GDM versus 48 pregnant healthy controls (HCs). We showed that the microbial and metabolic signatures of GDM patients were significantly different from those of HCs. Compared to HCs, the GDM subjects were characterized by enriched bacterial operational taxonomic units (OTUs) of the family Lachnospiraceae, and depleted OTUs of the families Enterobacteriaceae and Ruminococcaceae. Some altered gut microbes were significantly correlated with glucose values and fetal ultrasonography indexes. Moreover, we identified four fecal and 15 urine metabolites that discriminate GDM from HC. These differential metabolites are mainly involved in carbohydrate and amino acid metabolism. Significantly, co-occurrence network analysis revealed that Lachnospiraceae and Enterobacteriaceae bacterial OTUs formed strong co-occurring relationships with metabolites involved in carbohydrate and amino acid metabolism, suggesting that disturbed gut microbiome may mediate GDM. Furthermore, we identified a novel combinatorial marker panel that could distinguish GDM from HC subjects with high accuracy. Together our findings demonstrate that altered microbial composition and metabolic function may be relevant to the pathogenesis and pathophysiology of GDM.

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Section: Discussionmentioning

confidence: 88%

Altered gut bacterial and metabolic signatures and their interaction in gestational diabetes mellitus

Wang

Liu

et al. 2020

Gut Microbes

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“…Emerging data support a microbiome signature that defines liver cirrhosis and correlates with markers of liver disease severity [4][5][6][7] . Human studies are now attempting to define HCC microbial and metabolite signatures 8,9 whilst animal studies have implicated the gut microbiota and its metabolites in HCC pathogenesis through various mechanisms related to peripheral and intrahepatic inflammatory and immune responses [10][11][12] .…”

mentioning

confidence: 89%

Gut microbiota impact on the peripheral immune response in non-alcoholic fatty liver disease related hepatocellular carcinoma

et al. 2021

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The gut microbiota is reported to modulate the immune response in hepatocellular carcinoma (HCC). Here, we employ metagenomic and metabolomic studies to characterise gut microbiota in patients with non-alcoholic fatty liver disease (NAFLD) related cirrhosis, with or without HCC, and evaluate its effect on the peripheral immune response in an ex vivo model. We find that dysbiosis characterises the microbiota of patients with NAFLD-cirrhosis, with compositional and functional shifts occurring with HCC development. Gene function of the microbiota in NAFLD-HCC supports short chain fatty acid production, and this is confirmed by metabolomic studies. Ex vivo studies show that bacterial extracts from the NAFLD-HCC microbiota, but not from the control groups, elicit a T cell immunosuppressive phenotype, characterised by expansion of regulatory T cells and attenuation of CD8 + T cells. Our study suggest that the gut microbiota in NAFLD-HCC is characterised by a distinctive microbiome/metabolomic profile, and can modulate the peripheral immune response.

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“…A recent study by Oh T.G. et al demonstrated that a core gut microbiome signature can identify cirrhosis across separated cohorts, independent of disease etiology, host genetic, and environmental factors [ 131 ]. The identified disease microbiome included the elevated relative abundance of Veillonella parvula , Veillonella atypica , Ruminococcus gnavus , Clostridium bolteae , and Acidaminococcus sp.…”

Section: Potential Therapeutic Strategies and Non-invasive Diagnosmentioning

confidence: 99%

“…The identified disease microbiome included the elevated relative abundance of Veillonella parvula , Veillonella atypica , Ruminococcus gnavus , Clostridium bolteae , and Acidaminococcus sp. D21 and decreased abundance of Eubacterium eligens , Eubacterium rectale , and Faecalibacterium prausnitzii [ 131 ]. Although the results indicated the improved diagnostic accuracy in several cohorts, the authors claimed that these diagnostic methods need multi-center studies and well-phenotyped patients in order to be validated.…”

Section: Potential Therapeutic Strategies and Non-invasive Diagnosmentioning

confidence: 99%

Microbiota-Associated Therapy for Non-Alcoholic Steatohepatitis-Induced Liver Cancer: A Review

Chen

2020

IJMS

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Even though advancement in medicine has contributed to the control of many diseases to date, cancer therapy continues to pose several challenges. Hepatocellular carcinoma (HCC) etiology is multifactorial. Recently, non-alcoholic fatty liver disease (NAFLD) has been considered as an important risk factor of HCC. NAFLD can be divided into non-alcoholic simple fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH) based on histopathological features. Recently, studies have indicated that the gut microbiota is associated with NAFLD and HCC. Therefore, in this review, we have discussed the effects of gut microbiota-related mechanisms, including dysbiosis and gut barrier function, and gut microbiota-derived metabolites on NAFLD and HCC pathogenesis and the potential therapeutic strategies for NAFLD and HCC. With a better understanding of the gut microbiota composition and function, new and improved diagnostic, prognostic, and therapeutic strategies for common liver diseases can be developed.

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A Universal Gut-Microbiome-Derived Signature Predicts Cirrhosis

Cited by 222 publications

References 45 publications

Altered gut bacterial and metabolic signatures and their interaction in gestational diabetes mellitus

Altered gut bacterial and metabolic signatures and their interaction in gestational diabetes mellitus

Gut microbiota impact on the peripheral immune response in non-alcoholic fatty liver disease related hepatocellular carcinoma

Microbiota-Associated Therapy for Non-Alcoholic Steatohepatitis-Induced Liver Cancer: A Review

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