Intestinal Microbiome Shifts, Dysbiosis, Inflammation, and Non-alcoholic Fatty Liver Disease

Emma T. Saltzman, Talia Palacios, Michael Thomsen, Luis Vitetta

Adverse fluctuations in the distribution of the intestinal microbiome cohort has been associated with the onset of intra- and extra-intestinal inflammatory conditions, like the metabolic syndrome (MetS) and it's hepatic manifestation, non-alcoholic fatty liver disease (NAFLD). The intestinal microbial community of obese compared to lean subjects has been shown to undergo configurational shifts in various genera, including but not limited to increased abundances ofPrevotella, Escherichia, Peptoniphilus, andParabacteroidesand decreased levels ofBifidobacteria, Roseburia, andEubacteriagenera. At the phylum level, decreasedBacteroidetesand increasedFirmicuteshave been reported. The intestinal microbiota therefore presents an important target for designing novel therapeutic modalities that target extra-intestinal inflammatory disorders, such as NAFLD. This review hypothesizes that disruption of the intestinal-mucosal macrophage interface is a key factor in intestinal-liver axis disturbances. Intestinal immune responses implicated in the manifestation, maintenance and progression of NAFLD provide insights into the dialogue between the intestinal microbiome, the epithelia and mucosal immunity. The pro-inflammatory activity and immune imbalances implicated in NAFLD pathophysiology are reported to stem from dysbiosis of the intestinal epithelia which can serve as a source of hepatoxic effects. We posit that the hepatotoxic consequences of intestinal dysbiosis are compounded through intestinal microbiota-mediated inflammation of the local mucosa that encourages mucosal immune dysfunction, thus contributing important plausible insight in NAFLD pathogenesis. The administration of probiotics and prebiotics as a cure-all remedy for all chronic diseases is not advocated, instead, the incorporation of evidence based probiotic/prebiotic formulations as adjunctive modalities may enhance lifestyle modification management strategies for the amelioration of NAFLD.