Targeting gut-liver axis for the treatment of nonalcoholic steatohepatitis: translational and clinical evidence

• Published in: Translational research : the journal of laboratory and clinical medicine Vol. 167; no. 1; pp. 116 - 124
• Main Authors: Federico, Alessandro, Dallio, Marcello, Godos, Justyna, Loguercio, Carmela, Salomone, Federico
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-01-2016
• Subjects: Gastrointestinal Microbiome; Humans; Inflammation; Internal Medicine; Intestines - metabolism; Intestines - microbiology; Liver - metabolism; Liver - pathology; Non-alcoholic Fatty Liver Disease - etiology; Non-alcoholic Fatty Liver Disease - metabolism; Non-alcoholic Fatty Liver Disease - therapy; RES; NAFLD; nuclear transcriptional factor kappa-B; toll-like receptors; SIBO; transforming growth factor β; NF-kB; alanine aminotransferase; FIAF; fasting-induced adipose factor; ALT; damage associated molecular patterns; LPS; nonalcoholic steatohepatitis; BT; intestinal permeability; CFU; tumor necrosis factor alpha; bacterial translocation; PAMPs; TGF-β; TLR; tight junction; hepatic stellate cells; BMP; IM; IP; small intestinal bacteria overgrowth; NASH; bone morphogenetic protein; reticulumendothelial system; metabolic syndrome; intestinal microbiota; nonalcoholic fatty liver disease; pathogen-associated molecular patterns; MetS; TNF-α; TJ; colony-forming unit; HSCs; lipopolysaccharide; DAMP
• ISSN: 1931-5244; 1878-1810
• DOI: 10.1016/j.trsl.2015.08.002

Nonalcoholic fatty liver disease (NAFLD) is widely emerging as the most prevalent liver disorder and is associated with increased risk of liver-related and cardiovascular mortality. Recent experimental and clinical studies have revealed the pivotal role played by the alteration of gut-liver axis in the onset of fatty liver and related metabolic disturbances. Gut-liver cross talk is implicated not only in the impairment of lipid and glucose homeostasis leading to steatogenesis, but also in the initiation of inflammation and fibrogenesis, which characterize nonalcoholic steatohepatitis (NASH), the evolving form of NAFLD. The gut microbiota has been recognized as the key player in the gut-liver liaison and because of its complexity can act as a villain or a victim. Gut microbiota not only influences absorption and disposal of nutrients to the liver, but also conditions hepatic inflammation by supplying toll-like receptor ligands, which can stimulate liver cells to produce proinflammatory cytokines. Thus, the modification of intestinal bacterial flora by specific probiotics has been proposed as a therapeutic approach for the treatment of NASH. In this review, we summarized the evidence regarding the role of gut-liver axis in the pathogenesis of NASH and discussed the potential therapeutic role of gut microbiota modulation in the clinical setting.