Administration of Lactobacillus salivarius LI01 or Pediococcus pentosaceus LI05 prevents CCl4-induced liver cirrhosis by protecting the intestinal barrier in rats

Ding Shi,Feifei Guo,Daiqiong Fang,Lanjuan Li,Longxian Lv,Jianzhong Ye,Yating Li,Ang Li,Dewi Andayani,Wenrui Wu,Chenxia Hu,Lichen Xu,Xinjun Hu,Yanfei Chen,Jing Guo

doi:10.1038/s41598-017-07091-1

Ding Shi, Feifei Guo + Show 13 more

Open Access

https://doi.org/10.1038/s41598-017-07091-1

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Journal: Scientific Reports	Publication Date: Jul 31, 2017
Citations: 68	License type: open-access

Affiliation: Zhejiang University

Abstract

Alterations in the gut microbiome have been reported in liver cirrhosis, and probiotic interventions are considered a potential treatment strategy. This study aimed to evaluate the effects and mechanisms of Lactobacillus salivarius LI01, Pediococcus pentosaceus LI05, Lactobacillus rhamnosus GG, Clostridium butyricum MIYAIRI and Bacillus licheniformis Zhengchangsheng on CCl4-induced cirrhotic rats. Only administration of LI01 or LI05 prevented liver fibrosis and down-regulated the hepatic expression of profibrogenic genes. Serum endotoxins, bacterial translocations (BTs), and destruction of intestinal mucosal ultrastructure were reduced in rats treated with LI01 or LI05, indicating maintenance of the gut barrier as a mechanism; this was further confirmed by the reduction of not only hepatic inflammatory cytokines, such as TNF-α, IL-6, and IL-17A, but also hepatic TLR2, TLR4, TLR5 and TLR9. Metagenomic sequencing of 16S rRNA gene showed an increase in potential beneficial bacteria, such as Elusimicrobium and Prevotella, and a decrease in pathogenic bacteria, such as Escherichia. These alterations in gut microbiome were correlated with profibrogenic genes, gut barrier markers and inflammatory cytokines. In conclusion, L. salivarius LI01 and P. pentosaceus LI05 attenuated liver fibrosis by protecting the intestinal barrier and promoting microbiome health. These results suggest novel strategies for the prevention of liver cirrhosis.

Highlights

Alterations in the gut microbiome have been reported in liver cirrhosis, and probiotic interventions are considered a potential treatment strategy
Using immunohistochemical staining of α-SMA, a specific marker of activated hepatic stellate cell (HSC), we found that the α-SMA-positive areas were substantially reduced by administration of probiotic LI01 or LI05 (Fig. 1C,D), whereas the livers in other strain-treated groups exhibited no differences in α-SMA compared to those of the NS group
The major finding in the present study was that long-term administration of L. salivarius LI01 or P. pentosaceus LI05 prolonged the survival time and substantially ameliorated CCl4-induced liver cirrhosis in rats

Summary

Introduction

Alterations in the gut microbiome have been reported in liver cirrhosis, and probiotic interventions are considered a potential treatment strategy. Metagenomic sequencing of 16S rRNA gene showed an increase in potential beneficial bacteria, such as Elusimicrobium and Prevotella, and a decrease in pathogenic bacteria, such as Escherichia These alterations in gut microbiome were correlated with profibrogenic genes, gut barrier markers and inflammatory cytokines. L. salivarius LI01 and P. pentosaceus LI05 attenuated liver fibrosis by protecting the intestinal barrier and promoting microbiome health These results suggest novel strategies for the prevention of liver cirrhosis. Several opportunistic pathogenic bacteria from the phyla Firmicutes and Proteobacteria were enriched in the gut of primary biliary cirrhosis (PBC) patients and may be critical for the onset or development of PBC by interacting with metabolism and immunity[4]. We performed a comprehensive analysis of the gut flora, intestinal barrier, microbial molecular receptors, and inflammatory pathways to elucidate the mechanisms underlying the effects of specific probiotics on liver cirrhosis

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