Liver Steatosis, Gut-Liver Axis, Microbiome and Environmental Factors. A Never-Ending Bidirectional Cross-Talk

Abstract

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.

The Relationship between Prebiotic Supplementation and Anthropometric and Biochemical Parameters in Patients with NAFLD—A Systematic Review and Meta-Analysis of Randomized Controlled Trials

“…A meta-analysis of 21 randomized controlled trials found that fiber added to the diet restores bacterial homeostasis and thus promotes weight reduction [ 45 ]. Intestinal bacteria ( Lactobacillus and Bifidobacterium genera) have a positive effect on the reduction of the weight through a few mechanisms [ 45 , 53 , 54 ]: (i) reduction of inflammation and thus improvement of hypothalamic sensitivity to insulin; (ii) biotransformation of primary to secondary bile acids, which play an important role as signaling agents on both nuclear and membrane-associated intestinal and extra-intestinal receptors in enterohepatic circulation; (iii) stimulation of the secretion of certain intestinal hormones—peptide YY (PYYY) and glucagon-like peptide-1 (GLP-1) and GLP-2 (GLP-1 also suppresses the appetite by delaying gastric emptying and centrally promoting satiation) [ 54 , 55 ]; (iv) downregulating the expression of fasting-induced adipocyte factor (Fiaf) from gut epithelial cells, thus resulting in the degradation of lipoproteins and the deposition of free fatty acids in adipose tissue [ 56 ].…”

Regulation of Cholesterol Metabolism by Bioactive Components of Soy Proteins: Novel Translational Evidence

“…The effect of soy proteins might also involve the gut microbiota and bile acid homeostasis [ 65 , 66 ]. It has been found that the peptide IAVPGEVA significantly binds primary bile acid, cholic acid (CA), and secondary bile acid, deoxycholic acid (DCA) converted from CA by colonic microbiota [ 65 , 66 ] ( Figure 4 ).…”

“…The effect of soy proteins might also involve the gut microbiota and bile acid homeostasis [ 65 , 66 ]. It has been found that the peptide IAVPGEVA significantly binds primary bile acid, cholic acid (CA), and secondary bile acid, deoxycholic acid (DCA) converted from CA by colonic microbiota [ 65 , 66 ] ( Figure 4 ). The hypocholesterolemic effect of pepsin hydrolysate likely involves the binding of digested fragments of dietary fiber to bile acids, reducing bile acid reabsorption in the small and large intestines and increasing liver synthesis of bile acids from their precursor, cholesterol [ 67 ].…”

Helicobacter pylori Virulence Factors—Mechanisms of Bacterial Pathogenicity in the Gastric Microenvironment

“…The oral-to-oral and fecal-to-oral routes are two major transmission routes of the bacterium. The adaptation mechanisms of H. pylori include the bacterial and environmental factors that enable its survival in the gastric microenvironment where the acidity is at pH even lower than 3.0 [ 5 , 6 ]. The pathogenicity of H. pylori is associated with several mechanisms, among which the alterations of the host signaling pathways, indirect inflammatory responses induced within the gastric mucosa, and direct epigenetic outcomes on gastric epithelial cells, are of major importance [ 7 ].…”