Liver steatosis, gut-liver axis, microbiome and environmental factors. A never-ending bidirectional cross-talk

Agostino Di Ciaula, Jacek Baj, Gabriella Garruti, Giuseppe Celano, Maria De Angelis, Helen H. Wang, Domenica Maria Di Palo, Leonilde Bonfrate, David Q.H. Wang, Piero Portincasa

Research output: Contribution to journalReview articlepeer-review

85 Scopus citations


The prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing worldwide and parallels comorbidities such as obesity, metabolic syndrome, dyslipidemia, and diabetes. Recent studies describe the presence of NAFLD in non-obese individuals, with mechanisms partially independent from excessive caloric intake. Increasing evidences, in particular, point towards a close interaction between dietary and environmental factors (including food contaminants), gut, blood flow, and liver metabolism, with pathways involving intestinal permeability, the composition of gut microbiota, bacterial products, immunity, local, and systemic inflammation. These factors play a critical role in the maintenance of intestinal, liver, and metabolic homeostasis. An anomalous or imbalanced gut microbial composition may favor an increased intestinal permeability, predisposing to portal translocation of microorganisms, microbial products, and cell wall components. These components form microbial-associated molecular patterns (MAMPs) or pathogen-associated molecular patterns (PAMPs), with potentials to interact in the intestine lamina propria enriched in immune cells, and in the liver at the level of the immune cells, i.e., Kupffer cells and stellate cells. The resulting inflammatory environment ultimately leads to liver fibrosis with potentials to progression towards necrotic and fibrotic changes, cirrhosis. and hepatocellular carcinoma. By contrast, measures able to modulate the composition of gut microbiota and to preserve gut vascular barrier might prevent or reverse NAFLD.

Original languageEnglish (US)
Article number2648
Pages (from-to)1-44
Number of pages44
JournalJournal of Clinical Medicine
Issue number8
StatePublished - Aug 2020


  • Body weight
  • Fat
  • Fatty liver
  • Genetics
  • Intestinal permeability
  • Leaky gut

ASJC Scopus subject areas

  • General Medicine


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