Gut microbiome features associated with liver fibrosis in Hispanics, a population at high risk for fatty liver disease

Kwan, Suet-Ying; Jiao, Jingjing; Joon, Aron Y.; Wei, Peng; Petty, Lauren E.; Below, Jennifer E.; Daniel, Carrie R.; Wu, Xiaogang; Zhang, Jianhua; Jenq, Robert R.; Futreal, P. Andrew; Hawk, Ernest T.; McCormick, Joseph B.; Fisher‐Hoch, Susan P.

doi:10.1002/hep.32197

Cited by 29 publications

(31 citation statements)

References 57 publications

(75 reference statements)

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“…[ 15 ] Liver fibrosis is positively correlated with the abundance of Holdemanella biformis in a cohort of patients with high risk for fatty liver disease. [ 16 ] In addition, this species is also associated with colorectal cancer, inflammation‐related gastrointestinal diseases, and host lipid metabolism. [ 17 ] The expansion of Bilophila wadsworthia is associated with increased inflammation, intestinal barrier dysfunction, and bile acid dysmetabolism in host, leading to higher glucose dysmetabolism and hepatic steatosis.…”

Section: Resultsmentioning

confidence: 99%

Multiomics Analysis Reveals the Impact of Microbiota on Host Metabolism in Hepatic Steatosis

Zeybel

Arif

et al. 2022

Advanced Science

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Metabolic dysfunction-associated fatty liver disease (MAFLD) is a complex disease involving alterations in multiple biological processes regulated by the interactions between obesity, genetic background, and environmental factors including the microbiome. To decipher hepatic steatosis (HS) pathogenesis by excluding critical confounding factors including genetic variants and diabetes, 56 heterogenous MAFLD patients are characterized by generating multiomics data including oral and gut metagenomics as well as plasma metabolomics and inflammatory proteomics data. The dysbiosis in the oral and gut microbiome is explored and the host-microbiome interactions based on global metabolic and inflammatory processes are revealed. These multiomics data are integrated using the biological network and HS's key features are identified using multiomics data. HS is finally predicted using these key features and findings are validated in a follow-up cohort, where 22 subjects with varying degree of HS are characterized.

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Section: Resultsmentioning

confidence: 99%

Multiomics Analysis Reveals the Impact of Microbiota on Host Metabolism in Hepatic Steatosis

Zeybel

Arif

et al. 2022

Advanced Science

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“…The controlled attenuation parameter (CAP) has demonstrated good accuracy for reflecting NAFLD severity (18,19). In a recent study on gut microbiome (GM) signatures and the biological functions associated with liver fibrosis, Kwan et al (20) used FibroScan to screen for NAFLD. In the present study, CAP >236 (dB/m) was diagnostic for NAFLD.…”

Section: Inclusion Criteriamentioning

confidence: 99%

Alterations in the Gut Microbiota and Hepatitis-B-Virus Infection in Southern Chinese Patients With Coexisting Non-Alcoholic Fatty Liver Disease and Type-2 Diabetes Mellitus

Han

Huang

et al. 2021

Front. Med.

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Background: Hepatitis B virus (HBV) infection has been reported to affect the bacterial characteristics in the host. We aimed to elucidate the compositional and functional characteristics of the microbiota in southern Chinese patients with coexistent HBV infection, non-alcoholic fatty liver disease (NAFLD), and type-2 diabetes mellitus (T2DM).Methods: Healthy controls (HCs) and patients with coexistent NAFLD and T2DM were enrolled. Patients were divided into two groups: N1 (without HBV infection) and N2 (with HBV infection). Stool samples were collected for 16s RNA gene sequencing and untargeted metabolomics analysis.Results: Bacterial diversity was decreased in the N2 group. There was a significantly lower abundance of bacteria of Faecalibacterium, Gemmiger, and Clostridium_XIVA genera, but a higher abundance of Megamonas and Phascolarctobacterium genera in the N2 group. Compared with the N1 group, the abundance of Gemmiger species was even lower, and alterations in the abundance of Phascolarctobacterium and Clostridium_XIVA genera only occurred in the N2 group. There were significantly different fecal metabolic features, which were enriched in glucose and lipid metabolic pathways (e.g., fatty acid and glycerophospholipid metabolism) between the N2 and HC groups. Metabolites in glycerophospholipid metabolism, such as Sn-3-o-(geranylgeranyl)glycerol1-phosphate, were even higher in the N2 group than in the N1 group. The decreased Faecalibacterium and Gemmiger contributed to the increased level of Sn-3-o-(geranylgeranyl) glycerol1-phosphate, palmitoylcarnitine, and serum triglycerides. Clostridium_XIVA species were positively correlated to 15(s)-hpete. Megamonas species were positively correlated with the serum level of glucose indirectly.Conclusions: The distinct gut-microbiome profile associated with HBV infection has a role in lipid metabolism and glucose metabolism in patients with coexistent NAFLD and T2DM.Clinical Trial Registration:www.ClinicalTrials.gov, identifier: NCT03525769.

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“…Our team has previously described gut microbial signatures with robust diagnostic accuracy for advanced fibrosis and cirrhosis in NAFLD 6–8 . Gut microbial features have also been shown to be closely associated with liver fibrosis in a population‐based cohort of Hispanics, a patient population with high prevalence of NAFLD 12 . A number of the bacterial taxa that comprise our 13‐species microbial signature of decompensated NAFLD‐related cirrhosis overlap with those taxa previously associated with histologic phenotypes of NAFLD and/or cirrhosis 6,7,13–15 .…”

Section: Discussionmentioning

confidence: 99%

Gut metagenome‐derived signature predicts hepatic decompensation and mortality in NAFLD‐related cirrhosis

Sharpton

Madamba

et al. 2022

Aliment Pharmacol Ther

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Summary Background There are limited data on the diagnostic accuracy of gut microbial signatures for predicting hepatic decompensation in patients with cirrhosis. Aims To determine whether a stool metagenome‐derived signature accurately detects hepatic decompensation and mortality risk in cirrhosis secondary to non‐alcoholic fatty liver disease (NAFLD) Methods Shotgun metagenomic sequencing was performed on faecal samples collected at study entry from a prospective cohort of adults with NAFLD‐related cirrhosis. A Random Forest machine learning algorithm was utilised to identify a metagenomic signature of decompensated cirrhosis (defined by ascites, hepatic encephalopathy or variceal haemorrhage) and subsequently validated in an external cohort. A Cox proportional hazards regression model was used to examine predictors of all‐cause mortality. Results In all, 25 adults with NAFLD‐related cirrhosis (training cohort) were included. Among the 16 participants with decompensated cirrhosis, 33% had ascites, 56% had hepatic encephalopathy and 22% had experienced a variceal haemorrhage (not mutually exclusive). We identified a stool metagenomic signature comprising 13 discriminatory species that reliably distinguished decompensated NAFLD‐related cirrhosis (diagnostic accuracy, 0.97, 95% confidence interval [CI] 0.96–0.99). Diagnostic accuracy of the 13‐species signature remained high after adjustment for lactulose (area under the curve [AUC] 0.99) and rifaximin use (AUC 0.93). The discriminative ability of 13‐species metagenomic signature was robust in an independent test cohort (AUC 0.95, 95% CI 0.81–1.00). The 13‐species metagenomic signature (hazard ratio [HR] 1.54, 95% CI 1.10–2.15, p = 0.01) was a stronger predictor of mortality than the Model for End‐Stage Liver Disease score (HR 1.25, 95% CI 1.03–1.53, p = 0.03). Conclusions This study provides evidence for a gut metagenome‐derived signature with high diagnostic accuracy for hepatic decompensation that predicts risk of mortality in NAFLD‐related cirrhosis.

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Gut microbiome features associated with liver fibrosis in Hispanics, a population at high risk for fatty liver disease

Cited by 29 publications

References 57 publications

Multiomics Analysis Reveals the Impact of Microbiota on Host Metabolism in Hepatic Steatosis

Multiomics Analysis Reveals the Impact of Microbiota on Host Metabolism in Hepatic Steatosis

Alterations in the Gut Microbiota and Hepatitis-B-Virus Infection in Southern Chinese Patients With Coexisting Non-Alcoholic Fatty Liver Disease and Type-2 Diabetes Mellitus

Gut metagenome‐derived signature predicts hepatic decompensation and mortality in NAFLD‐related cirrhosis

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