Microbiota Modulation With Synbiotic Decreases Liver Fibrosis in a High Fat Choline Deficient Diet Mice Model of Non-Alcoholic Steatohepatitis (NASH).

Abstract

BACKGROUND:

Gut microbiota may play a role in non-alcoholic steatohepatitis (NASH). Previous studies showed that prebiotics and probiotics might halt the progression of steatohepatitis.

AIM:

To clarify the potential effect of Synbiotic 2000®Forte (Synb) in preventing or ameliorating diet induced steatohepatitis, particularly in fibrosis progression and how this intervention correlates with gut microbiota composition and endotoxinemia.

METHODS:

Twenty-seven C57BL/6 mice were divided into three groups: chow diet (CD, n = 7); high-fat choline deficient diet (HFCD, n = 10) and HFCD diet supplemented with Synbiotic 2000®Forte (four probiotic strains and four prebiotics mixture) (HFCD + Synb, n = 10). At 6 and 18 weeks, blood samples (lipopolysaccharides assay - LPS), cecal feaces (gut microbiota) and liver tissue (histology) were collected for analysis.

RESULTS:

Both HCFD diet mice developed steatohepatitis with ballooning at 6 and 18 weeks, opposite to CD. Comparison of histological scores in HFCD and HFCD + Synb, at 6 and 18 weeks showed no significant difference regarding steatosis, inflammation, or ballooning. Evaluating fibrosis with Sirius Red, and degree of smooth-muscle cell activation, HFCD mice had significantly more fibrosis; addition of Synb significantly reduced fibrosis at 6 weeks and 18 weeks. Serum endotoxin levels were similarly increased in HFCD and HFCD + Synb at week 6; however at week 18 HFCD + Synb had significantly lower endotoxin levels than HFCD. Gut microbiota of HFCD vs CD, showed no significant differences regarding the phyla Firmicutes and Bacteroidetes, either at 6 or 18 weeks; Proteobacteria increased at 6 week (3.3) and 18 week (7.5), while the addition of Synb resulted in a decrease at week 18 (-3.90). Fusobacteria markedly increase at week 18 (10.0), but less so with the addition of Synb (5.2).

CONCLUSION:

Synbiotic 2000®Forte is able to modulate the mouse gut microbiota reducing the degree of fibrosis while simultaneously decreasing endotoxemia.

• Authors: Helena Cortez-Pinto, Paula Borralho, Jorge Machado, Maria T Lopes, Inês V Gato, António M Santos, António S Guerreiro
• Journal: GE Portuguese journal of gastroenterology (GE Port J Gastroenterol) 2016 May-Jun Vol. 23 Issue 3 Pg. 132-141 ISSN: 2341-4545 [Print] Switzerland
• PMID: 28868449 (Publication Type: Journal Article)