Immunonutritional contribution of gut microbiota to fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) is indisputably the most widespread liver disease worldwide, leading to a significant increase in patient morbidity, mortality, and health care utilization. The gut microbiota and its genome (microbiome) have emerged as a novel modulator of the immunometabolic processes that NAFLD implies, but microbiota-targeted interventions have resulted both astounding and at the same time unsuccessful. The most relevant alteration appears to be the overgrowth of Gram-negative bacteria, characterized by an increased ratio of Firmicutes to Bacteroidetes, although current evidence indicates species- and strain-specific effects influencing energy harvest, the host's innate and adaptive immune systems, and epigenetic regulation as determinants of the immunomodulatory milieu in NAFLD. The genera Lactobacillus and Bifidobacterium deserve special attention since many of their probiotic strains are marketed for human consumption, even more so when considering that, in conjunction with prebiotics, they are potential modulators of gut microbiota composition and/or metabolic activity. Here, a better understanding of the major intestinal microbial factors with a detrimental or preventive role in NAFLD, and of the dynamic interplay between gut microbiome and host factors, appears crucial in defining the exposome for the prevention and treatment of NAFLD and associated diseases such as metabolic syndrome, type-2 diabetes, and obesity.