In other words, it is possible that broad societal changes have altered the gut microbiota in humans in a way that has driven the increased incidence of metabolic syndrome, including NAFLD. Evidence to support this possibility comes from studies in mice, in which loss of genes involved in innate immune detection of the microbiota result in altered gut microbiota composition that drives

increased activation of compensatory innate immune signaling pathways. These phenomena are associated with development of various aspects of metabolic syndrome that, in the context of a Western diet, result in NAFLD. For example, in the TLR5-deficient mice, an altered microbiota including

numerous bacterial species that were overrepresented or underrepresented was observed.[11] The role of specific INCB024360 order species was not evaluated but, overall, such altered microbiotas were shown to be sufficient to cause disease in that they could drive low-grade inflammation and metabolic disease upon transfer to wild-type germfree mice. Such transfer of microbiota to germfree mice simulates the acquisition of a microbiota at birth and thus these studies may reflect that see more acquired alterations in microbiota could be inherited and thus may be playing a role in the increased incidence of metabolic disease. While the extent to which the human microbiota has actually changed amid the increased incidence of NAFLD is not clear, one can point to one clear example of an altered microbiota over the last 75 years. Specifically, carriage rates of Helicobacter pylori have dropped

dramatically from about 80% to less than 5% of the native-born 20-year-olds. While medchemexpress loss of this one specific microbe, which of course has potential to cause disease, may or may not have any consequences relating to NAFLD, it may reflect that increased use of antibiotics and/or changes in hygiene/behavioral practices have resulted in broad changes in the microbiota that have played a role in increased incidence of NAFLD and other chronic inflammatory diseases. A related possibility is that the increased incidence of NAFLD may be analogous to a traditional infectious disease in that microbes that promote the disease may not be inherited but can be acquired from other persons. Various aspects of the epidemiology of NAFLD and other aspects of metabolic syndrome, particularly obesity, suggest that these disorders have characteristics of infectious disease and studies have associated carriage of select strains of adenoviruses with obesity.[50] Some of the strongest evidence that altered microbiota can promote NAFLD comes from recent mice studies by Flavell and colleagues.