Nonalcoholic fatty liver disease is associated with dysbiosis independent of body mass index and insulin resistance

Silva, Hannah E. Da; Teterina, Anastasia; Comelli, Elena M.; Taïbi, Amel; Arendt, Bianca M.; Fischer, Sandra E.; Lou, Wendy; Allard, Johane P.

doi:10.1038/s41598-018-19753-9

Cited by 225 publications

(247 citation statements)

References 61 publications

(88 reference statements)

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“…7 To date, only one study has examined the gut microbiota in non-obese adults and noted a significant reduction in Faecalibacterium 19 , which is consistent with findings in obese NASH. 12, 18 However, Lactobacillus and Ruminococcus were reduced in non-obese NASH, similar to findings in non-obese NAFL, and consistent with findings that these genera may have a role in weight regulation. 24, 25 …”

Section: Human Gut Microbiome Profiles In Clinical Phenotypes Of Naflsupporting

confidence: 83%

“…7–9, 11, 13, 17, 18, 21, 22 Results from fecal and serum metabolite profiling are listed in Table 1. To date, no human studies have functionally profiled the gut microbiome in NAFLD-related HCC.…”

Section: Human Gut Microbiome Profiles In Clinical Phenotypes Of Naflmentioning

confidence: 99%

“…11 Da Silva et al performed targeted profiling of eight fecal metabolites of interest and found that higher concentration of two fecal SCFAs, propionate and isobutyric acid, differentiated adults with NAFL from healthy controls, corroborating findings from Raman et al . 18 …”

Section: Human Gut Microbiome Profiles In Clinical Phenotypes Of Naflmentioning

confidence: 99%

“…11, 18 (Table 1) In both obesity and NAFLD, incongruous findings for the association between clinical phenotypes and SCFAs are likely attributable to the differential abundance of individual SCFAs, each of which may have different effects on host metabolism.…”

Section: Postulated Mechanisms Linking the Gut Microbiome To Nafldmentioning

confidence: 99%

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

Sharpton

Ajmera

Loomba

2019

Clinical Gastroenterology and Hepatology

144

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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.

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Section: Human Gut Microbiome Profiles In Clinical Phenotypes Of Naflsupporting

confidence: 83%

Section: Human Gut Microbiome Profiles In Clinical Phenotypes Of Naflmentioning

confidence: 99%

Section: Human Gut Microbiome Profiles In Clinical Phenotypes Of Naflmentioning

confidence: 99%

Section: Postulated Mechanisms Linking the Gut Microbiome To Nafldmentioning

confidence: 99%

See 2 more Smart Citations

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

Sharpton

Ajmera

Loomba

2019

Clinical Gastroenterology and Hepatology

144

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“…Dysbiosis, beyond the known risk factors for NAFLD, promotes the development of chronic liver diseases and HCC, independent of body mass index (BMI) and insulin resistance, producing a large amount of bioactive molecules, which deeply affect physiological and pathological body status [84] . Interestingly, in a mouse model, drugs able to modify the microbiome (e.g., rifaximin) may prevent HCC development.…”

Section: Pathogenesismentioning

confidence: 99%

Fat and hepatocellular carcinoma

Balsano¹,

Porcu²,

Sideri³

et al. 2018

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Obesity and diabetes are associated with the onset of hepatocellular carcinoma (HCC). These two illnesses correlate also with the development of non-alcoholic fatty liver disease (NAFLD). Currently, NAFL is considered the leading form of chronic liver disease in the Western industrialized countries. Insulin resistance is the common pathogenic factor among these three pathologies. NAFL is characterized by fat accumulation in the liver that involves greater than 5% of the liver parenchyma with no evidence of hepatocyte injury. However, NAFL may progress toward non-alcoholic steatohepatitis that in turn may lead to advanced fibrosis, cirrhosis and HCC. It is alarming that NAFLD related HCC has been, at present, considered as a growing burden worldwide, and its prevalence is tending to further increase together with the increasing incidence of obesity and diabetes. Worthy of note is that in the presence of chronic accumulation of fat in the liver it has been reported the emergence of HCC during chronic liver disease in absence of liver cirrhosis, usually the major risk factor for the development of HCC. Thus, in the future NAFLD related HCCs will place a growing strain on health-care systems from the need for their management. Unfortunately, most of the NAFLD related HCC patients are diagnosed at advanced stages and are characterized by a poor prognosis, because they are ineligible to radical treatments. Thus, it is urgent to boost up new screening policies to make early diagnoses, as well as to develop preventive-therapeutic strategies.

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Microbiomics, Metabolomics, Predicted Metagenomics, and Hepatic Steatosis in a Population‐Based Study of 1,355 Adults

et al. 2021

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Background and Aims Previous small studies have appraised the gut microbiome (GM) in steatosis, but large‐scale studies are lacking. We studied the association of the GM diversity and composition, plasma metabolites, predicted functional metagenomics, and steatosis. Approach and Results This is a cross‐sectional analysis of the prospective population‐based Rotterdam Study. We used 16S ribosomal RNA gene sequencing and determined taxonomy using the SILVA reference database. Alpha diversity and beta diversity were calculated using the Shannon diversity index and Bray–Curtis dissimilarities. Differences were tested across steatosis using permutational multivariate analysis of variance. Hepatic steatosis was diagnosed by ultrasonography. We subsequently selected genera using regularized regression. The functional metagenome was predicted based on the GM using Kyoto Encyclopedia of Genes and Genomes pathways. Serum metabolomics were assessed using high‐throughput proton nuclear magnetic resonance. All analyses were adjusted for age, sex, body mass index, alcohol, diet, and proton‐pump inhibitors. We included 1,355 participants, of whom 472 had steatosis. Alpha diversity was lower in steatosis (P = 1.1∙10−9), and beta diversity varied across steatosis strata (P = 0.001). Lasso selected 37 genera of which three remained significantly associated after adjustment (Coprococcus3: β = −65; Ruminococcus Gauvreauiigroup: β = 62; and Ruminococcus Gnavusgroup: β = 45, Q‐value = 0.037). Predicted metagenome analyses revealed that pathways of secondary bile‐acid synthesis and biotin metabolism were present, and D‐alanine metabolism was absent in steatosis. Metabolic profiles showed positive associations for aromatic and branched chain amino acids and glycoprotein acetyls with steatosis and R. Gnavusgroup, whereas these metabolites were inversely associated with alpha diversity and Coprococcus3. Conclusions We confirmed, on a large‐scale, the lower microbial diversity and association of Coprococcus and Ruminococcus Gnavus with steatosis. We additionally showed that steatosis and alpha diversity share opposite metabolic profiles.

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Nonalcoholic fatty liver disease is associated with dysbiosis independent of body mass index and insulin resistance

Cited by 225 publications

References 61 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

Fat and hepatocellular carcinoma

Microbiomics, Metabolomics, Predicted Metagenomics, and Hepatic Steatosis in a Population‐Based Study of 1,355 Adults

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