The role of the gut microbiota in NAFLD

Abstract

NAFLD is now the most common cause of liver disease in Western countries. This Review explores the links between NAFLD, the metabolic syndrome, dysbiosis, poor diet and gut health. Animal studies in which the gut microbiota are manipulated, and observational studies in patients with NAFLD, have provided considerable evidence that dysbiosis contributes to the pathogenesis of NAFLD. Dysbiosis increases gut permeability to bacterial products and increases hepatic exposure to injurious substances that increase hepatic inflammation and fibrosis. Dysbiosis, combined with poor diet, also changes luminal metabolism of food substrates, such as increased production of certain short-chain fatty acids and alcohol, and depletion of choline. Changes to the microbiome can also cause dysmotility, gut inflammation and other immunological changes in the gut that might contribute to liver injury. Evidence also suggests that certain food components and lifestyle factors, which are known to influence the severity of NAFLD, do so at least in part by changing the gut microbiota. Improved methods of analysis of the gut microbiome, and greater understanding of interactions between dysbiosis, diet, environmental factors and their effects on the gut-liver axis should improve the treatment of this common liver disease and its associated disorders.

Microbial modulation of cardiovascular disease

“…Although still controversial, there is also a growing body of literature suggesting that increased permeability of oral and intestinal epithelial barriers may enable a small number of bacteria to enter into the systemic circulation, where they can ultimately enter into host tissues to promote disease 9–11 . Whether residing in or on exposed surfaces, or when they access the systemic circulation, bacteria can directly engage the innate immune system to not only elicit appropriate bacteriocidal responses, but to also regulate host metabolism and inflammatory pathways relevant to CVD.…”

“…The products of gut microbial fermentation are by far the most well-studied gut microbial metabolites, having key roles in both the maintenance of gut microbial ecology, and in fine-tuning host immunity and metabolic disease 100–104 . The major products of microbial fermentation of dietary fibers are SCFAs, with the most abundant metabolites being acetate, butyrate and proprionate.…”

Developmental origins of NAFLD: a womb with a clue

“…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 .…”

Food Additives and Contaminants: Effects on Human Gut Microbiota—A Review

“…The GM play an important role in several human diseases, such as obesity [4,5], diabetes [6,7], cancer [8,9], cardiovascular diseases [10] metabolic syndrome [1,3,11] non-alcoholic fatty liver disease [12,13] and in several psychiatric disorders [14,15]. Gut microbes produce a large number of bioactive compounds that can influence human health.…”