Hepatocellular carcinoma is associated with gut microbiota profile and inflammation in nonalcoholic fatty liver disease

Francesca Romana Ponziani, Sherrie Bhoori, Chiara Castelli, Lorenza Putignani, Licia Rivoltini, Federica Del Chierico, Maurizio Sanguinetti, Daniele Morelli, Francesco Paroni Sterbini, Valentina Petito, Sofia Reddel, Riccardo Calvani, Chiara Camisaschi, Anna Picca, Alessandra Tuccitto, Antonio Gasbarrini, Maurizio Pompili, Vincenzo Mazzaferro

Research output: Contribution to journalArticle

Abstract

The gut-liver axis plays a pivotal role in the pathogenesis of nonalcoholic fatty liver disease (NAFLD), which is the third leading cause of hepatocellular carcinoma (HCC) worldwide. However, the link between gut microbiota and hepatocarcinogenesis remains to be clarified. The aim of this study was to explore what features of the gut microbiota are associated with HCC in patients with cirrhosis and NAFLD. A consecutive series of patients with NAFLD-related cirrhosis and HCC (group 1, 21 patients), NAFLD-related cirrhosis without HCC (group 2, 20 patients), and healthy controls (group 3, 20 patients) was studied for gut microbiota profile, intestinal permeability, inflammatory status, and circulating mononuclear cells. We finally constructed a model depicting the most relevant correlations among these features, possibly involved in hepatocarcinogenesis. Patients with HCC showed increased levels of fecal calprotectin, while intestinal permeability was similar to patients with cirrhosis but without HCC. Plasma levels of interleukin 8 (IL8), IL13, chemokine (C-C motif) ligand (CCL) 3, CCL4, and CCL5 were higher in the HCC group and associated with an activated status of circulating monocytes. The fecal microbiota of the whole group of patients with cirrhosis showed higher abundance of Enterobacteriaceae and Streptococcus and a reduction in Akkermansia. Bacteroides and Ruminococcaceae were increased in the HCC group, while Bifidobacterium was reduced. Akkermansia and Bifidobacterium were inversely correlated with calprotectin concentration, which in turn was associated with humoral and cellular inflammatory markers. A similar behavior was also observed for Bacteroides.

CONCLUSION: Our results suggest that in patients with cirrhosis and NAFLD the gut microbiota profile and systemic inflammation are significantly correlated and can concur in the process of hepatocarcinogenesis. (Hepatology 2018).

Original languageEnglish
Number of pages14
JournalHepatology
DOIs
Publication statusE-pub ahead of print - Apr 17 2018

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Hepatocellular Carcinoma
Inflammation
Fibrosis
Leukocyte L1 Antigen Complex
Bacteroides
Bifidobacterium
Permeability
Chemokine CCL3
Gastrointestinal Microbiome
Non-alcoholic Fatty Liver Disease
Interleukin-13
Microbiota
Gastroenterology
Enterobacteriaceae
Streptococcus
Interleukin-8
Monocytes
Control Groups
Liver

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Hepatocellular carcinoma is associated with gut microbiota profile and inflammation in nonalcoholic fatty liver disease. / Ponziani, Francesca Romana; Bhoori, Sherrie; Castelli, Chiara; Putignani, Lorenza; Rivoltini, Licia; Del Chierico, Federica; Sanguinetti, Maurizio; Morelli, Daniele; Paroni Sterbini, Francesco; Petito, Valentina; Reddel, Sofia; Calvani, Riccardo; Camisaschi, Chiara; Picca, Anna; Tuccitto, Alessandra; Gasbarrini, Antonio; Pompili, Maurizio; Mazzaferro, Vincenzo.

In: Hepatology, 17.04.2018.

Research output: Contribution to journalArticle

Ponziani, Francesca Romana ; Bhoori, Sherrie ; Castelli, Chiara ; Putignani, Lorenza ; Rivoltini, Licia ; Del Chierico, Federica ; Sanguinetti, Maurizio ; Morelli, Daniele ; Paroni Sterbini, Francesco ; Petito, Valentina ; Reddel, Sofia ; Calvani, Riccardo ; Camisaschi, Chiara ; Picca, Anna ; Tuccitto, Alessandra ; Gasbarrini, Antonio ; Pompili, Maurizio ; Mazzaferro, Vincenzo. / Hepatocellular carcinoma is associated with gut microbiota profile and inflammation in nonalcoholic fatty liver disease. In: Hepatology. 2018.
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abstract = "The gut-liver axis plays a pivotal role in the pathogenesis of nonalcoholic fatty liver disease (NAFLD), which is the third leading cause of hepatocellular carcinoma (HCC) worldwide. However, the link between gut microbiota and hepatocarcinogenesis remains to be clarified. The aim of this study was to explore what features of the gut microbiota are associated with HCC in patients with cirrhosis and NAFLD. A consecutive series of patients with NAFLD-related cirrhosis and HCC (group 1, 21 patients), NAFLD-related cirrhosis without HCC (group 2, 20 patients), and healthy controls (group 3, 20 patients) was studied for gut microbiota profile, intestinal permeability, inflammatory status, and circulating mononuclear cells. We finally constructed a model depicting the most relevant correlations among these features, possibly involved in hepatocarcinogenesis. Patients with HCC showed increased levels of fecal calprotectin, while intestinal permeability was similar to patients with cirrhosis but without HCC. Plasma levels of interleukin 8 (IL8), IL13, chemokine (C-C motif) ligand (CCL) 3, CCL4, and CCL5 were higher in the HCC group and associated with an activated status of circulating monocytes. The fecal microbiota of the whole group of patients with cirrhosis showed higher abundance of Enterobacteriaceae and Streptococcus and a reduction in Akkermansia. Bacteroides and Ruminococcaceae were increased in the HCC group, while Bifidobacterium was reduced. Akkermansia and Bifidobacterium were inversely correlated with calprotectin concentration, which in turn was associated with humoral and cellular inflammatory markers. A similar behavior was also observed for Bacteroides.CONCLUSION: Our results suggest that in patients with cirrhosis and NAFLD the gut microbiota profile and systemic inflammation are significantly correlated and can concur in the process of hepatocarcinogenesis. (Hepatology 2018).",
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T1 - Hepatocellular carcinoma is associated with gut microbiota profile and inflammation in nonalcoholic fatty liver disease

AU - Ponziani, Francesca Romana

AU - Bhoori, Sherrie

AU - Castelli, Chiara

AU - Putignani, Lorenza

AU - Rivoltini, Licia

AU - Del Chierico, Federica

AU - Sanguinetti, Maurizio

AU - Morelli, Daniele

AU - Paroni Sterbini, Francesco

AU - Petito, Valentina

AU - Reddel, Sofia

AU - Calvani, Riccardo

AU - Camisaschi, Chiara

AU - Picca, Anna

AU - Tuccitto, Alessandra

AU - Gasbarrini, Antonio

AU - Pompili, Maurizio

AU - Mazzaferro, Vincenzo

N1 - © 2018 by the American Association for the Study of Liver Diseases.

PY - 2018/4/17

Y1 - 2018/4/17

N2 - The gut-liver axis plays a pivotal role in the pathogenesis of nonalcoholic fatty liver disease (NAFLD), which is the third leading cause of hepatocellular carcinoma (HCC) worldwide. However, the link between gut microbiota and hepatocarcinogenesis remains to be clarified. The aim of this study was to explore what features of the gut microbiota are associated with HCC in patients with cirrhosis and NAFLD. A consecutive series of patients with NAFLD-related cirrhosis and HCC (group 1, 21 patients), NAFLD-related cirrhosis without HCC (group 2, 20 patients), and healthy controls (group 3, 20 patients) was studied for gut microbiota profile, intestinal permeability, inflammatory status, and circulating mononuclear cells. We finally constructed a model depicting the most relevant correlations among these features, possibly involved in hepatocarcinogenesis. Patients with HCC showed increased levels of fecal calprotectin, while intestinal permeability was similar to patients with cirrhosis but without HCC. Plasma levels of interleukin 8 (IL8), IL13, chemokine (C-C motif) ligand (CCL) 3, CCL4, and CCL5 were higher in the HCC group and associated with an activated status of circulating monocytes. The fecal microbiota of the whole group of patients with cirrhosis showed higher abundance of Enterobacteriaceae and Streptococcus and a reduction in Akkermansia. Bacteroides and Ruminococcaceae were increased in the HCC group, while Bifidobacterium was reduced. Akkermansia and Bifidobacterium were inversely correlated with calprotectin concentration, which in turn was associated with humoral and cellular inflammatory markers. A similar behavior was also observed for Bacteroides.CONCLUSION: Our results suggest that in patients with cirrhosis and NAFLD the gut microbiota profile and systemic inflammation are significantly correlated and can concur in the process of hepatocarcinogenesis. (Hepatology 2018).

AB - The gut-liver axis plays a pivotal role in the pathogenesis of nonalcoholic fatty liver disease (NAFLD), which is the third leading cause of hepatocellular carcinoma (HCC) worldwide. However, the link between gut microbiota and hepatocarcinogenesis remains to be clarified. The aim of this study was to explore what features of the gut microbiota are associated with HCC in patients with cirrhosis and NAFLD. A consecutive series of patients with NAFLD-related cirrhosis and HCC (group 1, 21 patients), NAFLD-related cirrhosis without HCC (group 2, 20 patients), and healthy controls (group 3, 20 patients) was studied for gut microbiota profile, intestinal permeability, inflammatory status, and circulating mononuclear cells. We finally constructed a model depicting the most relevant correlations among these features, possibly involved in hepatocarcinogenesis. Patients with HCC showed increased levels of fecal calprotectin, while intestinal permeability was similar to patients with cirrhosis but without HCC. Plasma levels of interleukin 8 (IL8), IL13, chemokine (C-C motif) ligand (CCL) 3, CCL4, and CCL5 were higher in the HCC group and associated with an activated status of circulating monocytes. The fecal microbiota of the whole group of patients with cirrhosis showed higher abundance of Enterobacteriaceae and Streptococcus and a reduction in Akkermansia. Bacteroides and Ruminococcaceae were increased in the HCC group, while Bifidobacterium was reduced. Akkermansia and Bifidobacterium were inversely correlated with calprotectin concentration, which in turn was associated with humoral and cellular inflammatory markers. A similar behavior was also observed for Bacteroides.CONCLUSION: Our results suggest that in patients with cirrhosis and NAFLD the gut microbiota profile and systemic inflammation are significantly correlated and can concur in the process of hepatocarcinogenesis. (Hepatology 2018).

U2 - 10.1002/hep.30036

DO - 10.1002/hep.30036

M3 - Article

C2 - 29665135

JO - Hepatology

JF - Hepatology

SN - 0270-9139

ER -