In patients with metabolic syndrome, nonalcoholic fatty liver disease can lead to cirrhosis and other hepatic disorders. In Nature, Flavell and colleagues show that the NLRP3 and NLRP6 inflammasomes and the effector cytokine IL-18 regulate the progression of nonalcoholic fatty liver disease. Various mouse models show that inflammasome deficiency induces changes in the gut microbiota that are associated with more influx of bacterial products into the portal circulation, activation of the Toll-like receptors TLR5 and TLR9 and enhanced expression of tumor necrosis factor in the liver. The changes in microbiota composition involve over-representation of bacteria of the family Porphyromonadaceae, combined with alterations in organisms of other taxa. Some metabolic aberrations associated with the altered gut microbiota, such as obesity, can be horizontally transferred to other mice. These results demonstrate a complex and cooperative effect of two families of sensors, the NLRs and TLRs, in shaping metabolic events.

Nature 482, 179–185 (2012)