Abstract
Non-alcoholic fatty liver disease (NAFLD) is a spectrum of disorders, ranging from fatty liver to a more insulin resistant, inflammatory and fibrotic state collectively termed non-alcoholic steatohepatitis (NASH). In the United States, 30%–40% of the adult population has fatty liver and 3%–12% has NASH, making it a major public health concern. Consumption of diets high in fat, obesity and Type II diabetes (T2D) are well-established risk factors; however, there is a growing body of literature suggesting a role for the gut microbiome in the development and progression of NAFLD. The gut microbiota is separated from the body by a monolayer of intestinal epithelial cells (IECs) that line the small intestine and colon. The IEC layer is exposed to luminal contents, participates in selective uptake of nutrients and acts as a barrier to passive paracellular permeability of luminal contents through the expression of tight junctions (TJs) between adjacent IECs. A dysbiotic gut microbiome also leads to decreased gut barrier function by disrupting TJs and the gut vascular barrier (GVB), thus exposing the liver to microbial endotoxins. These endotoxins activate hepatic Toll-like receptors (TLRs), further promoting the progression of fatty liver to a more inflammatory and fibrotic NASH phenotype. This review will summarize major findings pertaining to aforementioned gut-liver interactions and its role in the pathophysiology of NAFLD.
Highlights
Non-alcoholic fatty liver disease (NAFLD), once known as the “un-named” disease, afflicts 80–100 million Americans and is currently the most common cause of chronic liver disease [1]
In addition to carbon tracing, another angle would be examining the effect of short chain fatty acids (SCFAs) on inhibition of histone deacetylases (HDACs), as it has been demonstrated that SCFAs like butyrate inhibit HDACs to activatethe transcription of activators of fatty acid oxidation such as peroxisome proliferator-activated receptor (PPAR)-a
Alterations in the gut microbiome have been correlated with NAFLD progression
Summary
Non-alcoholic fatty liver disease (NAFLD), once known as the “un-named” disease, afflicts 80–100 million Americans and is currently the most common cause of chronic liver disease [1]. About 20%– 30% of NAFLD cases in the United States fall under the more severe category of non-alcoholic steatohepatitis (NASH) [1]. No therapies are currently approved for treatment or prevention of NAFLD/NASH. Development of such a therapeutic requires more in depth understanding of this disease, including answers to questions such as: What factors influence progression of steatosis to NASH, to NASH with fibrosis? What predisposes 30% of NAFLD patients to develop NASH? Can we harness pre-disposing factors and other non-invasive methods to accurately predict disease progression? Development of such a therapeutic requires more in depth understanding of this disease, including answers to questions such as: What factors influence progression of steatosis to NASH, to NASH with fibrosis? What predisposes 30% of NAFLD patients to develop NASH? Can we harness pre-disposing factors and other non-invasive methods to accurately predict disease progression?
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