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Symbiotic formulation in experimentally induced liver fibrosis in rats: intestinal microbiota as a key point to treat liver damage?
Author(s) -
D'Argenio Giuseppe,
Cariello Rita,
Tuccillo Concetta,
Mazzone Giovanna,
Federico Alessandro,
Funaro Annalisa,
Magistris Laura,
Grossi Enzo,
Callegari Maria L.,
Chirico Marilena,
Caporaso Nicola,
Romano Marco,
Morelli Lorenzo,
Loguercio Carmela
Publication year - 2013
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/liv.12117
Subject(s) - fibrosis , intestinal permeability , medicine , cytokine , basal (medicine) , liver fibrosis , biology , endocrinology , insulin
Aim Evidence indicates that intestinal microbiota may participate in both the induction and the progression of liver damage. The aim of our research was the detection and evaluation of the effects of chronic treatment with a symbiotic formulation on CCl 4 ‐induced rat liver fibrosis. Results CCl 4 significantly increased gastric permeability in respect to basal values, and the treatment with symbiotic significantly decreased it. CCl 4 per se induced a decrease in intestinal permeability. This effect was also seen in fibrotic rats treated with symbiotic and was still evident when normal rats were treated with symbiotic alone ( P < 0.001 in all cases). Circulating levels of pro‐inflammatory cytokine TNF ‐α were significantly increased in rats with liver fibrosis as compared with normal rats, while symbiotic treatment normalized the plasma levels of TNF ‐α and significantly enhanced anti‐inflammatory cytokine IL 10. TNF ‐α, TGF ‐β, TLR 4, TLR 2, i NOS and α‐ SMA m RNA expression in the liver were up‐regulated in rats with CCl 4 ‐induced liver fibrosis and down‐regulated by symbiotic treatment. Moreover, IL ‐10 and e NOS m RNA levels were increased in the CCL 4 + symbiotic group. Symbiotic treatment of fibrotic rats normalized serum ALT , AST and improved histology and liver collagen deposition. DGGE analysis of faecal samples revealed that CCl 4 administration and symbiotic treatment either alone or in combination produced modifications in faecal profiles vs controls. Conclusions Our results provide evidence that in CCl 4 ‐induced liver fibrosis, significant changes in gastro‐intestinal permeability and in faecal flora occur. Treatment with a specific symbiotic formulation significantly affects these changes, leading to improvement in both liver inflammation and fibrosis.