Microbiota in the pathogenesis of systemic autoinflammatory and metabolic disorders

Changes in gut-microbiota–host interactions, due to impaired NLRP3 and NLRP6 inflammasome sensing, could explain the rate of progression of multiple abnormalities associated with the metabolic syndrome, such as the progression from nonalcoholic fatty liver disease to nonalcoholic steatohepatitis. In mice, alterations caused by inflammasome deficiency were associated with exacerbated hepatic steatosis and inflammation, through influx of TLR4 and TLR9 agonists into the portal circulation, which increased hepatic TNF expression and induced progression to nonalcoholic steatohepatitis.