1Division of Gastroenterology and Hepatology, Houston Methodist Hospital and Weill Cornell Medical College, Houston, Texas.
With the recognition of the various metabolic functions of the gut microbiome and of its putative role in obesity, an investigation of the contribution of the bacterial populations of the gastrointestinal tract to the metabolic syndrome and its hepatic manifestation-nonalcoholic liver disease (NAFLD)-became inevitable. Furthermore, the central role of an altered microbiome in the precipitation of infectious and noninfectious complications of liver disease was described decades ago. The contribution of the microbiome to the pathogenesis of NAFLD has been extensively studied in animal models. Convincing evidence for a central role for an altered microbiome (through multiple mechanisms), coupled with such phenomena as impaired gut barrier function and an aberrant host immune response, has been amply demonstrated. The accumulation of a similar level of evidence from human studies has proven more challenging; however, incriminating data accumulate. Although animal studies have demonstrated the benefits of interventions that modulate the microbiome and of probiotics, in particular, in reducing steatosis and preventing progression to steatohepatitis, data in man are scanty and high-quality clinical trials of probiotics and other strategies are needed.