Potential Beneficial Effect of Rifaximin in the Prevention of Hepatocellular Carcinoma through the Modulation of the Microbiota in an Experimental Model of Non-alcoholic Fatty Liver Disease

Authors

  • Jéssica Tonin Ferrari Graduate Program in Gastroenterology and Hepatology, Universidade Federal do Rio Grande do Sul, Porto Alegre. Rio Grande do Sul, Brazil. https://orcid.org/0000-0003-4022-5362
  • Gabriel Tayguara Silveira Guerreiro Graduate Program in Gastroenterology and Hepatology, Universidade Federal do Rio Grande do Sul, Porto Alegre. Rio Grande do Sul, Brazil. https://orcid.org/0000-0002-0550-4561
  • Larisse Graduate Program in Gastroenterology and Hepatology, Universidade Federal do Rio Grande do Sul, Porto Alegre. Rio Grande do Sul, Brazil. https://orcid.org/0000-0002-4453-7227
  • Themis Reverbel da Silveira Experimental Laboratory of Hepatology and Gastroenterology, Center for Experimental Research, Hospital de Clínicas de Porto Alegre, Porto Alegre. Rio Grande do Sul, Brazil.
  • Carlos Thadeu Schmidt Cerski Graduate Program in Gastroenterology and Hepatology, Universidade Federal do Rio Grande do Sul, Porto Alegre. Rio Grande do Sul, Brazil.
  • Erica Tozawa Unit of Surgical Pathology, Hospital de Clínicas de Porto Alegre, Porto Alegre. Rio Grande do Sul, Brazil. https://orcid.org/0000-0002-3021-4435
  • Cláudia P Oliveira Department of Gastroenterology (LIM07), Faculdade de Medicina da Universidade de São Paulo. São Paulo, Brazil. https://orcid.org/0000-0002-2848-417X
  • Mário Reis Álvares-da-Silva Graduate Program in Gastroenterology and Hepatology, Universidade Federal do Rio Grande do Sul, Porto Alegre. Rio Grande do Sul, Brazil. https://orcid.org/0000-0002-5001-246X
  • Carolina Uribe-Cruz Graduate Program in Gastroenterology and Hepatology, Universidade Federal do Rio Grande do Sul, Porto Alegre. Rio Grande do Sul, Brazil. https://orcid.org/0000-0002-0526-3067

DOI:

https://doi.org/10.52787/agl.v53i3.329

Keywords:

Gut microbiota, hepatocellular carcinoma, non-alcoholic fatty liver disease, rifaximin

Abstract

Aim. To evaluate the effects of rifaximin through microbiota modulation in a model of hepatocellular carcinoma secondary to non-alcoholic fatty liver disease.

Methods. Three groups of 8 adult male Sprague-Dawley rats each were divided as follows: the HCC group: rats fed a high-fat and choline-deficient diet plus diethylnitrosamine as a carcinogen, the hepatocellular carcinoma treated group: rats fed a high-fat and choline-deficient diet plus diethylnitrosamine and treated with rifaximin and the control group: animals fed standard diet and water. The rats were euthanized after 16 weeks. We performed analyses of liver pathology for non-alcoholic fatty liver disease severity and cancer grading, gene expression in intestinal and hepatic tissues and fecal microbiota.

Results. All animals in the hepatocellular carcinoma group had non-alcoholic fatty liver disease and developed hepatocellular carcinoma lesions. Rifaximin animals showed less intense non-alcoholic fatty liver disease (assessed by non-alcoholic fatty liver disease activity score [NAS]) compared to the hepatocellular carcinoma group. Both the hepatocellular carcinoma and hepatocellular carcinoma + rifaximin groups showed areas of fibrosis as assessed by picrosirius red. Three animals in the rifaximin group did not develop cancerous lesions. Gut microbiota analyses revealed differences in diversity and composition in the control group vs hepatocellular carcinoma and rifaximin groups. Twelve differentially abundant genera were identified between the hepatocellular carcinoma and rifaximin groups. In the rifaximin group, gene expression of intestinal tight junctions decreased.

Conclusions. In a rodent model of non-alcoholic fatty liver disease-related hepatocellular carcinoma, rifaximin reduces the histological severity of non-alcoholic fatty liver dis-
ease and the occurrence of hepatocellular carcinoma, probably by modulating the gut microbiota independently of markers of intestinal permeability.

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2023-09-30

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Tonin Ferrari, J., Tayguara Silveira Guerreiro, G., Longo, L., Reverbel da Silveira, T., Thadeu Schmidt Cerski, C., Tozawa, E., P Oliveira, C., Reis Álvares-da-Silva, M., & Uribe-Cruz, C. (2023). Potential Beneficial Effect of Rifaximin in the Prevention of Hepatocellular Carcinoma through the Modulation of the Microbiota in an Experimental Model of Non-alcoholic Fatty Liver Disease. Acta Gastroenterológica Latinoamericana, 53(3), 265–282. https://doi.org/10.52787/agl.v53i3.329

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Vol. 53 No. 3 (2023): Acta Gastroenterológica Latinoamericana

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Copyright (c) 2023 Jéssica Tonin Ferrari, Gabriel Tayguara Silveira Guerreiro, Larisse Longo, Themis Reverbel da Silveira, Carlos Thadeu Schmidt Cerski, Erica Tozawa, Cláudia P Oliveira, Mário Reis Álvares-da-Silva, Carolina Uribe-Cruz

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