Gut Microbiome-Based Metagenomic Signature for Non-invasive Detection of Advanced Fibrosis in Human Nonalcoholic Fatty Liver Disease

Loomba, Rohit; Seguritan, Victor; Li, Weizhong; Long, Tao; Klitgord, Niels; Bhatt, Archana; Dulai, Parambir S.; Caussy, Cyrielle; Bettencourt, Richele; Highlander, Sarah K.; Jones, Marcus B.; Sirlin, Claude B.; Schnabl, Bernd; Brinkac, Lauren; Schork, Nicholas J.; Chen, Chi‐Hua; Brenner, David A.; Biggs, William H.; Yooseph, Shibu; Venter, J. Craig; Nelson, Karen E.

doi:10.1016/j.cmet.2017.04.001

Cited by 855 publications

(903 citation statements)

References 46 publications

Supporting

Mentioning

837

Contrasting

Unclassified

Order By: Relevance

“…utilized shotgun metagenomic sequencing, thus allowing for species level resolution, and noted that Bacteroides vulgatus and Escherichia coli were the most abundant species in patients with NAFLD-related advanced fibrosis. 17 This finding is concordant with a prior observation that Bacteroides vulgatus is a contributor to insulin resistance. 28 Due to utilization of 16S rRNA sequencing in other human studies examining advanced fibrosis, comparisons with these species-level findings are not feasible.…”

Section: Human Gut Microbiome Profiles In Clinical Phenotypes Of Naflsupporting

confidence: 91%

Emerging Role of the Gut Microbiome in Nonalcoholic Fatty Liver Disease: From Composition to Function

Sharpton

Ajmera

Loomba

2019

Clinical Gastroenterology and Hepatology

Self Cite

144

View full text Add to dashboard Cite

The gut microbiome, a diverse microbial community in the gastrointestinal tract, plays a pivotal role in the maintenance of health. The gut microbiome metabolizes dietary and host-derived molecules to produce bioactive metabolites, which have a wide array of effects on host metabolism and immunity. 'Dysbiosis' of the gut microbiome, commonly considered as perturbation of microbiome diversity and composition, has been associated with intestinal and extra-intestinal diseases, including nonalcoholic fatty liver disease (NAFLD). A number of endogenous and exogenous factors, such as nutritional intake and xenobiotic exposure, can alter the gut microbiome. We will review the evolving methods for studying the gut microbiome and how these profiling techniques have been utilized to further our understanding of the gut microbial community composition and functional potential in the clinical spectrum of NAFLD. We will highlight microbiome-host interactions that may contribute to the pathogenesis of NAFLD, with a primary focus on mechanisms related to the metabolic output of the gut microbiome. Finally, we will discuss potential therapeutic implications of the gut microbiome in NAFLD.

show abstract

Section: Human Gut Microbiome Profiles In Clinical Phenotypes Of Naflsupporting

confidence: 91%

Emerging Role of the Gut Microbiome in Nonalcoholic Fatty Liver Disease: From Composition to Function

Sharpton

Ajmera

Loomba

2019

Clinical Gastroenterology and Hepatology

Self Cite

144

View full text Add to dashboard Cite

show abstract

“…Inosine and hypoxanthine (associated with nucleoside metabolism) are enriched in serum samples from patients with mild or moderate NAFLD (stage 0–2 fibrosis), whereas succinate, malate, α-ketoglutarate, glutamine, serine, fumarate, α-ketobutyrate, glutamate and lactate (associated with amino acid and carbon metabolism) are enriched in serum samples from patients with advanced fibrosis (stages 3–4) 44. A recent study also showed that severity of liver steatosis correlates with phenylacetic acid in humans 50.…”

Section: Metabolomic Studies Of Nafldmentioning

confidence: 99%

“…Clinical studies demonstrate that formate and acetate are enriched in faecal samples from adults with advanced fibrosis, whereas butyrate and propionate are enriched in faecal samples from adults with mild or moderate NAFLD 44. It therefore appears that levels and subtypes of SCFAs correlate with the severity of fatty liver disease.…”

Section: Microbiota-derived Metabolites In Nafldmentioning

confidence: 99%

Small metabolites, possible big changes: a microbiota-centered view of non-alcoholic fatty liver disease

Chu

Duan

Yang

et al. 2018

Gut

Self Cite

271

209

View full text Add to dashboard Cite

The spectrum of non-alcoholic fatty liver disease (NAFLD) ranges from simple hepatic steatosis, commonly associated with obesity, to non-alcoholic steatohepatitis, which can progress to fibrosis, cirrhosis and hepatocellular carcinoma. NAFLD pathophysiology involves environmental, genetic and metabolic factors, as well as changes in the intestinal microbiota and their products. Dysfunction of the intestinal barrier can contribute to NAFLD development and progression. Although there are technical limitations in assessing intestinal permeability in humans and the number of patients in these studies is rather small, fewer than half of the patients have increased intestinal permeability and translocation of bacterial products. Microbe-derived metabolites and the signalling pathways they affect might play more important roles in development of NAFLD. We review the microbial metabolites that contribute to the development of NAFLD, such as trimethylamine, bile acids, short-chain fatty acids and ethanol. We discuss the mechanisms by which metabolites produced by microbes might affect disease progression and/or serve as therapeutic targets or biomarkers for NAFLD.

show abstract

“…They included 86 biopsy-proven NAFLD patietns (14 with stage 3 or 4 fibrosis). Using a metagenomic profile of 37 selected species along with age, BMI and diversity, they generated a model with an AUC of 0.936 to differentiate between early and advanced fibrosis in NAFLD 18 . The predicted metabolite functional change was not significant between groups but advanced fibrosis NAFLD patients had higher 3-phenylpropanoate, a product of anaerobic bacterial metabolism.…”

Section: Introductionmentioning

confidence: 99%

Altered Microbiome in Patients With Cirrhosis and Complications

Acharya

Bajaj

2019

Clinical Gastroenterology and Hepatology

123

View full text Add to dashboard Cite

The microbiome in cirrhosis is affected by multiple processes occurring at the level of the gut and systemically. This dysbiosis, or unfavorable microbiota profile, is present at several body sites and is associated with higher systemic inflammation, bacterial infections and poor outcomes. This increased morbidity in cirrhosis stems from an immune paralysis state that is partly related to the constant stimulation of the immune system by this dysbiosis. Dysbiosis as a dynamic event worsens with decompensation such as with hepatic encephalopathy, infections or acute-on-chronic liver failure (ACLF). These microbial patterns could be applied as diagnostic and prognostic measures in cirrhosis in the outpatient and inpatient setting. Current therapies for cirrhosis have differing impacts on gut microbial composition and functionality. Dietary modifications and the oral cavity have emerged as newer targetable factors to modulate the microbiome, which could affect inflammation and, potentially improve outcomes. Additionally, fecal microbial transplant is being increasingly studied to provide compositional and functional modulation of the microbiome. Ultimately, a combination of targeted therapies may be needed to provide an optimal gut milieu to improve outcomes in cirrhosis.

show abstract

Gut Microbiome-Based Metagenomic Signature for Non-invasive Detection of Advanced Fibrosis in Human Nonalcoholic Fatty Liver Disease

Cited by 855 publications

References 46 publications

Emerging Role of the Gut Microbiome in Nonalcoholic Fatty Liver Disease: From Composition to Function

Emerging Role of the Gut Microbiome in Nonalcoholic Fatty Liver Disease: From Composition to Function

Small metabolites, possible big changes: a microbiota-centered view of non-alcoholic fatty liver disease

Altered Microbiome in Patients With Cirrhosis and Complications

Contact Info

Product

Resources

About