Analysis of the Relationship Between the Degree of Dysbiosis in Gut Microbiota and Prognosis at Different Stages of Primary Hepatocellular Carcinoma.

Jiajia Ni,Min Yu,Qiao Li,Xiaoping Xu,Baohua Hou,Xiaoxia Chen,Mei Ge,Huifang Zhou,Peihua Cao,Kebo Zhong,Rong Huang,Yi Gao,Baogang Peng,Peng Zhang,Yang Li

doi:10.3389/fmicb.2019.01458

Abstract

Gut microbiota dysbiosis is closely associated with primary hepatocellular carcinoma (HCC). Recent studies have evaluated the early diagnosis of primary HCC through analysis of gut microbiota dysbiosis. However, the relationship between the degree of dysbiosis and the prognosis of primary HCC remains unclear. Because primary HCC is accompanied by dysbiosis and dysbiosis usually increases the circulatory concentrations of endotoxin and other harmful bacterial substances, which further increases liver damage, we hypothesized that level of dysbiosis associated with primary HCC increases with the stage of cancer progression. To test this hypothesis, we introduced a more integrated index referred to as the degree of dysbiosis (Ddys); and we investigated Ddys of the gut microbiota with the development of primary HCC through high-throughput sequencing of 16S rRNA gene amplicons. Our results showed that compared with healthy individuals, patients with primary HCC showed increased pro-inflammatory bacteria in their fecal microbiota. The Ddys increased significantly in patients with primary HCC compared with that in healthy controls. Moreover, there was a tendency for the Ddys to increase with the development of primary HCC, although no significant difference was detected between different stages of primary HCC. Our findings provide important insights into the use of gut microbiota analysis during the treatment of primary HCC.

Highlights

Disruption of the gut microbiota is closely associated with the development of chronic liver diseases (CLDs) in humans and rodent models (Aron-Wisnewsky et al, 2013; Grice and Segre, 2013; Kamada et al, 2013; Schnabl, 2013; Bajaj et al, 2014a; Grat et al, 2016; Houghton et al, 2016; Shen et al, 2017)
Proteobacteria Were Increased in the Gut Microbiota of Patients With Primary hepatocellular carcinoma (HCC)
The increase in degree of dysbiosis (Ddys) was continued, and a tendency of Ddys to increase emerged with the progression of primary HCC, no significant difference was detected between patients with different stages of primary HCC (Figure 3D)

Summary

Introduction

Disruption of the gut microbiota (termed “dysbiosis”) is closely associated with the development of chronic liver diseases (CLDs) in humans and rodent models (Aron-Wisnewsky et al, 2013; Grice and Segre, 2013; Kamada et al, 2013; Schnabl, 2013; Bajaj et al, 2014a; Grat et al, 2016; Houghton et al, 2016; Shen et al, 2017). Patients with chronic hepatitis or decompensated cirrhosis secondary to hepatitis B infection showed reduced numbers of probiotic Bifidobacteria and lactic acid-producing bacteria in the feces, whereas Enterococcus faecalis and Enterobacteriaceae numbers were higher than those in asymptomatic carriers and healthy controls (Lu et al, 2011). Increases in Streptococcaceae, Veillonellaceae, and Enterobacteriaceae, accompanied by a decrease in Lachnospiraceae, characterize the gut microbiota in cirrhosis. The relative abundances of the Lachnospiraceae and Streptococcaceae families were negatively and positively related with the ChildPugh score in patients with cirrhosis, respectively (Chen et al, 2011)

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Discussion

Conclusion