Microbiome Signatures Associated With Steatohepatitis and Moderate to Severe Fibrosis in Children With Nonalcoholic Fatty Liver Disease

Schwimmer, Jeffrey B.; Johnson, Jethro; Ángeles, Jorge; Behling, Cynthia; Belt, Patricia; Borecki, Ingrid B.; Bross, Craig; Durelle, Janis; Goyal, Nidhi; Hamilton, Gavin; Holtz, Mary L.; Lavine, Joel E.; Mitreva, Makedonka; Newton, Kimberly P.; Pan, Amy; Simpson, Pippa; Sirlin, Claude B.; Sodergren, Erica; Tyagi, Rahul; Yates, Katherine P.; Weinstock, George M.; Salzman, Nita H.

doi:10.1053/j.gastro.2019.06.028

Cited by 209 publications

(209 citation statements)

References 55 publications

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“…Moreover, the authors found an elevated production of secondary bile acids from CRC metagenomes, suggesting a metabolic link between cancer-associated gut microbes and a fat-and meat-rich diet. In line with other studies showing gut microbiome signatures driven by specific diseases [160,161], Wirbel et al established CRC-specific microbiome signatures distinct from other conditions such as type 2 diabetes, Parkinson's disease, and inflammatory bowel disease. Notably, the gut microbiome of CRC cases showed a higher diversity as compared to controls, which was explained by the translocation of microbes from the oral cavity into the colon.…”

Section: Consequences Of Altered Intestinal Homeostasis: Correlationsupporting

confidence: 76%

Dietary Factors in the Control of Gut Homeostasis, Intestinal Stem Cells, and Colorectal Cancer

2019

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Colorectal cancer (CRC) is the third commonly diagnosed cancer and the second leading cause of cancer-related deaths worldwide. Global CRC burden is expected to increase by 60% in the next decade, with low-income countries experiencing an escalation of CRC incidence and mortality in parallel to the adoption of western lifestyles. CRC incidence is also sharply increasing in individuals younger than 50 years, often presenting at advanced stages and with aggressive features. Both genetic and environmental factors have been recognized as major contributors for the development of CRC, the latter including diet-related conditions such as chronic inflammation and obesity. In particular, a diet rich in fat and sugars (Western-style diet, WSD) has been shown to induce multiple pathophysiological changes in the intestine linked to an increased risk of CRC. In this scenario, dietary factors have been recently shown to play novel unexpected roles in the regulation of intestinal stem cells (ISCs) and of the gut microbiota, which represent the two main biological systems responsible for intestinal homeostasis. Furthermore, diet is increasingly recognized to play a key role in the neoplastic transformation of ISCs and in the metabolic regulation of colorectal cancer stem cells. This review illustrates novel discoveries on the role of dietary components in regulating intestinal homeostasis and colorectal tumorigenesis. Particular focus is dedicated to new areas of research with potential clinical relevance including the effect of food components on ISCs and cancer stem cells (CSCs), the existence of CRC-specific microbial signatures and the alterations of intestinal homeostasis potentially involved in early-onset CRC. New insights on the role of dietary factors in intestinal regulation will provide new tools not only for the prevention and early diagnosis of CRC but also for improving the effectiveness of current CRC therapies.

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Section: Consequences Of Altered Intestinal Homeostasis: Correlationsupporting

confidence: 76%

Dietary Factors in the Control of Gut Homeostasis, Intestinal Stem Cells, and Colorectal Cancer

2019

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“…Therefore, studies that have compared individuals with biopsy-proven NASH to a no-biopsy obese control group might have been biased by un-diagnosed NASH among the controls. Currently, there are few studies with biopsy-proven NAFL or NASH [15][16][17][18], and only one study was conducted with biopsy-proven healthy individuals [15]. Therefore, the present study has a homogeneous, well characterized and correctly diagnosed population by biopsy-proven NAFL patients, NASH patients, and healthy individuals in Asia that gives value to the results.…”

Section: Discussionmentioning

confidence: 93%

“…Animal experiments in which the microbiome has been manipulated have shown that the gut microbiota plays an important role in the pathogenesis of NAFLD [13,14]. Nevertheless, only a few studies have linked gut dysbiosis with the severity of NAFLD in humans [15][16][17][18]. These studies had small sample sizes, heterogeneous populations, and divergent tools for gut microbiota analysis.…”

Section: Introductionmentioning

confidence: 99%

Gut Microbiota Dysbiosis in Patients with Biopsy-Proven Nonalcoholic Fatty Liver Disease: A Cross-Sectional Study in Taiwan

et al. 2020

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The gut microbiota plays a role in nonalcoholic fatty liver disease (NAFLD), but data about gut dysbiosis in Asians with NAFLD remains scarce. We analyzed the differences in fecal microbiota between adults with and without NAFLD. This cross-sectional study examined adults with histology-proven NAFLD (25 nonalcoholic fatty liver (NAFL) patients, 25 nonalcoholic steatohepatitis (NASH) patients, and 25 living liver donors (healthy controls)). The taxonomic composition of the gut microbiota was determined by 16S ribosomal RNA gene sequencing of stool samples. The NAFL and NASH groups showed lower total bacterial diversity and richness than the controls. NAFLD patients had higher levels of the phylum Bacteroidetes and lower levels of Firmicutes than controls. The genus Ruminococcaceae UCG-010, family Ruminococcaceae, order Clostridiales, and class Clostridia were less abundant in patients with NAFL or NASH than healthy individuals. The lipopolysaccharide biosynthesis pathway was differentially enriched in the NASH group. This study examined the largest number of Asian patients with biopsy-proven NAFL and NASH in terms of dysbiosis of the gut microbiota in NAFLD patients. NAFLD patients had higher levels of Bacteroidetes and lower levels of Firmicutes. These results are different from research from western countries and could provide different targets for therapies by region.

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“…There is increasing reports that the intestinal microbiome plays an important role in the pathogenesis of NAFLD. Animal models and human volunteer clinical studies have provided considerable information on the association between dysbiosis and NAFLD pathogenesis 57‐60 . However, less is known about the mechanisms involved in the bidirectional liver‐gut microbiome axis and how dysbiosis in the gastrointestinal tract contributes to the incidence of NAFLD.…”

Section: Discussionmentioning

confidence: 99%

Characterization of the variability in the extent of nonalcoholic fatty liver induced by a high‐fat diet in the genetically diverse Collaborative Cross mouse model

et al. 2020

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Interindividual variability and sexual dimorphisms in the development of nonalcoholic fatty liver disease (NAFLD) are still poorly understood. In the present study, male and female strains of Collaborative Cross (CC) mice were fed a high‐fat and high‐sucrose (HF/HS) diet or a control diet for 12 weeks to investigate interindividual‐ and sex‐specific variations in the development of NAFLD. The severity of liver steatosis varied between sexes and individual strains and was accompanied by an elevation of serum markers of insulin resistance, including increases in total cholesterol, low‐density lipoproteins, high‐density lipoproteins, phospholipids, and glucose. The development of NAFLD was associated with overexpression of the critical fatty acid uptake and de novo lipogenesis genes Pparg, Mogat1, Cd36, Acaab1, Fabp2, and Gdf15 in male and female mice. The expression of Pparg, Mogat1, and Cd36 was positively correlated with liver triglycerides in male mice, and Mogat1 and Cd36 expression were positively correlated with liver triglycerides in female mice. Our results indicate the value of CC mice in combination with HF/HS diet‐induced alterations as an approach to study the susceptibility and interindividual variabilities in the pathogenesis of nonalcoholic fatty liver and early nonalcoholic steatohepatitis at the population level, uncovering of susceptible and resistant cohorts, and identifying sex‐specific molecular determinants of disease susceptibility.

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Microbiome Signatures Associated With Steatohepatitis and Moderate to Severe Fibrosis in Children With Nonalcoholic Fatty Liver Disease

Cited by 209 publications

References 55 publications

Dietary Factors in the Control of Gut Homeostasis, Intestinal Stem Cells, and Colorectal Cancer

Dietary Factors in the Control of Gut Homeostasis, Intestinal Stem Cells, and Colorectal Cancer

Gut Microbiota Dysbiosis in Patients with Biopsy-Proven Nonalcoholic Fatty Liver Disease: A Cross-Sectional Study in Taiwan

Characterization of the variability in the extent of nonalcoholic fatty liver induced by a high‐fat diet in the genetically diverse Collaborative Cross mouse model

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