Abstract
Method This study included 74 Chinese male patients with HCC. They were divided into early (n = 19), intermediate (n = 37), and terminal (n = 18) groups, referred to as Barcelona Clinic Liver Cancer stage 0+A, B, and C+D, respectively. Paired fecal and plasma samples were collected. Microbial composition and profiles were analyzed by 16S rRNA gene sequencing. The levels of gut damage marker (regenerating islet-derived protein 3α (REG3α)) and microbial translocation markers (soluble CD14 (sCD14), lipopolysaccharide-binding protein (LBP), peptidoglycan recognition proteins (PGRPs)) were determined in plasma samples of patients by ELISA. Twenty plasma cytokine and chemokines were determined by Luminex. Results In early, intermediate, and terminal groups, the abundance of the Bifidobacteriaceae family decreased significantly (3.52%, 1.55%, and 0.56%, respectively, P = 0.003), while the abundance of the Enterococcaceae family increased significantly (1.6%, 2.9%, and 13.4%, respectively, P = 0.022). Levels of REG3α and sCD14 were markedly elevated only in the terminal group compared with the early (P = 0.025 and P = 0.048) and intermediate groups (P = 0.023 and P = 0.046). The level of LBP significantly increased in the intermediate (P = 0.035) and terminal (P = 0.025) groups compared with the early group. The PGRP levels were elevated only in the terminal group compared with the early group (P = 0.018). The ratio of Enterococcaceae to Bifidobacteriaceae was significantly associated with the levels of REG3α, LBP, sCD14, and PGRPs. With HCC progression, increased levels of inflammatory cytokines accompanied by a T cell-immunosuppressive response and microbial translocation were observed. Conclusion Gut microbiota compositional and functional shift, together with elevated gut damage and microbial translocation, may promote HCC development by stimulating inflammatory response and suppressing T cell response.
Highlights
Hepatocellular carcinoma (HCC) is the third leading cause of cancer mortality worldwide [1]
These results suggested that hepatocellular carcinoma (HCC) progression was characterized by an elevated inflammatory response and suppressed T cell immune responses
The ratio of Enterococcaceae to Bifidobacteriaceae was associated with the expression of gut damage marker Regenerating islet-derived protein 3α Soluble CD14 (sCD14) (REG3α) (r = 0:366, P = 0:003) and bacterial translocation markers, sCD14 (r = 0:322, P = 0:008), lipopolysaccharide-binding protein (LBP) (r = 0:386, P = 0:001), and peptidoglycan recognition proteins (PGRPs) (r = 0:405, P = 0:001; Table 2)
Summary
Hepatocellular carcinoma (HCC) is the third leading cause of cancer mortality worldwide [1]. Increasing evidence has indicated the relationship between dysbiosis of gut microbiome and HCC development [2,3,4]. Gut permeability was found to correlate with HCC. A recent study reported that gut permeability was significantly higher in patients with. The effect of microbial translocation on cirrhosis was well studied [10], but was not researched in HCC. This crosssectional study is aimed at evaluating microbiome dysbiosis, gut damage, and microbial translocation in 74 male patients in different stages of HCC. It was speculated that dysbiosis together with increased microbial translocation might impact HCC progression by regulating systemic inflammation and immune response
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