Systematic review: microbial dysbiosis and nonalcoholic fatty liver disease

Wieland, Amanda; Frank, Daniel N.; Harnke, Ben; Bambha, Kiran

doi:10.1111/apt.13376

Cited by 177 publications

(165 citation statements)

References 80 publications

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“…The human gut microbiota contains more than 100 fold genes than its host [16] and has been suggested to be an important environmental factor involved in the pathogenesis of NAFLD [17,18]. There is an anatomical link between the intestine and liver via the hepatic portal system.…”

Section: Introductionmentioning

confidence: 99%

Microbial Intervention as a Novel Target in Treatment of Non-Alcoholic Fatty Liver Disease Progression

Zhou

Zheng

Chen

et al. 2018

Cell Physiol Biochem

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Background/Aims: Emerging evidence suggests a close link between gut microbiota and non-alcoholic fatty liver disease (NAFLD). In this study, we aimed to investigate the association between gut microbiota and the DNA methylation of adiponectin (an adipocyte-specific adipocytokine) in rats, following diet-induced NAFLD. Methods: 50 male SD rats were randomly divided into five groups with or without a high fat diet (HFD), antibiotics, and probiotics, in order to establish an imbalanced gut microbiota and probiotic treatment model in NAFLD rats. After 13 weeks of treatment, blood, liver, and cecal tissue samples were collected. Serum lipids, liver function indexes by biochemical analyzers, and changes in liver pathology with hematoxylin-eosin (HE) and masson staining were detected. Furthermore, the serum adiponectin by enzyme-linked immunosorbent assay (ELISA) and liver adiponectin methylation levels in the promoter regions by pyrophosphate sequencing were determined. High throughput Illumina sequencing targeted microbial 16S genes, bioinformatics and statistical analysis identified cecal-associated gut microbiota. Results: HFD with antibiotic exposure showed the most severe steatohepatitis and a severe gut microbiota alteration. Reduced bacterial diversity was also seen and the abundances of Firmicutes, Lactobacillus, Cyanobacteria, Acidobacteria, Chlamydiae, Chlamydiales, Rubrobacteria, Verrucomicrobia, Blautia, Shewanella, Bacteroides, Bacteroides acidifaciens, and Bacteroides uniformis, were shown to be partly reversed by probiotic treatment. Decreased serum adiponectin levels and increased DNA methylation levels of adiponectin promoter regions were also markedly associated with the NAFLD progression during gut microbiota alteration. Conclusion: Our results suggested that both gut microbiota alteration and adiponectin variability may be drivers of NAFLD progression and that targeting the gut microbiota, such as via administration of a probiotic, may delay NAFLD progression via adiponectin.

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Section: Introductionmentioning

confidence: 99%

Microbial Intervention as a Novel Target in Treatment of Non-Alcoholic Fatty Liver Disease Progression

Zhou

Zheng

Chen

et al. 2018

Cell Physiol Biochem

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“…Whether the observed increased levels of blood-ethanol in NASH patients are a consequence of endogenous production by gut microbiota is still a subject of debate [98,99]. A recent systematic review addressing the association of dysbiotic microbiota composition with NAFLD concluded an association but no evidence for causality [100]. However, recent animal models demonstrate how the innate immunity (toll-like and NOD-like receptors) of gut epithelium critically regulates the gut microbiota, thereby controlling the progression of NAFLD and NASH.…”

Section: Antibiotics - Friend or Foe In The Pathogenesis And Course Omentioning

confidence: 99%

Effects of Antibiotics on Gut Microbiota

Lange

Buerger²,

Stallmach³

et al. 2016

Dig Dis

474

311

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The gut microbiota influences essential human functions including digestion, energy metabolism, and inflammation by modulating multiple endocrine, neural, and immune pathways of the host. Its composition and complexity varies markedly across individuals and across different sites of the gut, but provides a certain level of resilience against external perturbation. Short-term antibiotic treatment is able to shift the gut microbiota to long-term alternative dysbiotic states, which may promote the development and aggravation of disease. Common features of post-antibiotic dysbiosis include a loss of taxonomic and functional diversity combined with reduced colonization resistance against invading pathogens, which harbors the danger of antimicrobial resistance. This review summarizes the antibiotic-related changes of the gut microbiota and potential consequences in health and disease.

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“…2). Emerging evidence suggests that the severity of NAFLD postnatally is strongly associated with gut dysbiosis 99 and a shift in gut metabolic function, including production and utilization of shortchain fatty acids (SCFAs) and bile acids 100–103 . The functions of SCFAs and bile acids in NAFLD have been reviewed elsewhere 104 .…”

Section: Early Postnatal Factorsmentioning

confidence: 99%

Developmental origins of NAFLD: a womb with a clue

Wesolowski

Kasmi

Jonscher

et al. 2016

Nat Rev Gastroenterol Hepatol

175

167

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Changes in the maternal environment leading to an altered intrauterine milieu can result in subtle insults to the fetus, promoting increased lifetime disease risk and/or disease acceleration in childhood and later in life. Particularly worrisome is that the prevalence of NAFLD is rapidly increasing among children and adults, and is being diagnosed at increasingly younger ages, pointing towards an early-life origin. A wealth of evidence, in humans and non-human primates, suggests that maternal nutrition affects the placenta and fetal tissues, leading to persistent changes in hepatic metabolism, mitochondrial function, the intestinal microbiota, liver macrophage activation and susceptibility to NASH postnatally. Deleterious exposures in utero include fetal hypoxia, increased nutrient supply, inflammation and altered gut microbiota that might produce metabolic clues, including fatty acids, metabolites, endotoxins, bile acids and cytokines, which prime the infant liver for NAFLD in a persistent manner and increase susceptibility to NASH. Mechanistic links to early disease pathways might involve shifts in lipid metabolism, mitochondrial dysfunction, pioneering gut microorganisms, macrophage programming and epigenetic changes that alter the liver microenvironment, favouring liver injury. In this Review, we discuss how maternal, fetal, neonatal and infant exposures provide developmental clues and mechanisms to help explain NAFLD acceleration and increased disease prevalence. Mechanisms identified in clinical and preclinical models suggest important opportunities for prevention and intervention that could slow down the growing epidemic of NAFLD in the next generation.NAFLD is a general term used to describe a broad spectrum of liver abnormalities, ranging from simple, uncomplicated hepatic steatosis to NASH, accompanied by different degrees of Correspondence to J.E.F. jed.friedman@ucdenver.edu. Author contributionsAll authors researched data for the article, provided a substantial contribution to discussion of content, wrote the article, and reviewed and edited the manuscript before submission. Competing interests statementThe authors declare no competing interests. HHS Public AccessAuthor manuscript Nat Rev Gastroenterol Hepatol. Author manuscript; available in PMC 2017 December 12. Author Manuscript Author ManuscriptAuthor ManuscriptAuthor Manuscript inflammation and fibrosis. NAFLD is increasing in prevalence, especially in adolescents 1 , despite the levellingoff of the obesity epidemic from 2003-2004 to 2013-2014 in children and adolescents aged 2-19 years (REF.2). The most common chronic liver disease worldwide, NAFLD increases the risk of cardiovascular events eightfold and type 2 diabetes mellitus (T2DM) threefold 3 , and is a strong risk factor for hepatocellular carcinoma (HCC) 4 . At the time of paediatric NAFLD diagnosis, 25-50% of children have NASH and 10-25% have advanced fibrosis 5 . For many decades, it was thought that NAFLD was predominantly driven by obesity in the setting of genetic suscep...

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Systematic review: microbial dysbiosis and nonalcoholic fatty liver disease

Cited by 177 publications

References 80 publications

Microbial Intervention as a Novel Target in Treatment of Non-Alcoholic Fatty Liver Disease Progression

Microbial Intervention as a Novel Target in Treatment of Non-Alcoholic Fatty Liver Disease Progression

Effects of Antibiotics on Gut Microbiota

Developmental origins of NAFLD: a womb with a clue

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