Proton Pump Inhibitor Pantoprazole Modulates Intestinal Microbiota and Induces TLR4 Signaling and Fibrosis in Mouse Liver

Autor(es)

Assalin, Heloisa B. ; Gabriel De Almeida, Kelly Cristiane ; Guadagnini, Dioze ; Santos, Andrey ; Teixeira, Caio J. ; Bordin, Silvana ; Rocha, Guilherme Z. ; Saad, Mario J. A.

• Tipo de documento: Artigo Científico
• Fonte: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; v. 23, n. 22, p. 18-pg., 2022-11-01.

Resumo

Proton pump inhibitors (PPIs) are one of the most prescribed drugs around the world. PPIs induce microbiota modulation such as obesity both in humans and in animal models. However, since PPIs can induce microbiota modulation despite the absence of a high-fat diet or weight gain, it is an interesting model to correlate microbiota modulation with the establishment of non-alcoholic fatty liver disease (NAFLD). We investigated the effect of pantoprazole treatment on TLR4 signaling and liver histology in C57BL/6J mice for 60 days, trying to correlate microbiota modulation with some aspects of liver injury. We performed glucose (GTT) and insulin (ITT) tolerance tests, serum lipopolysaccharide (LPS) dosage, liver histology, liver and intestine extraction for Western blot and qPCR. Fecal microbiota were investigated via metagenomics. Chronic treatment with pantoprazole induced microbiota modulation and impaired ileum barrier integrity, without an association with insulin resistance. Furthermore, increased circulating LPS and increased Toll-like receptor 4 (TLR4) and TGF beta downstream signaling may have an important role in the development of the observed liver microvesicular steatosis and fibrosis. Finally, this model of PPI-induced changes in microbiota might be useful to investigate liver microvesicular steatosis and fibrosis. (AU)

• Processo FAPESP: 19/03196-0 - Mecanismos moleculares envolvidos na inflexibilidade metabólica de ratos submetidos à programação fetal por excesso de glicocorticoides
• Beneficiário: Silvana Auxiliadora Bordin da Silva
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 14/50907-5 - INCT 2014 - de obesidade e diabetes
• Beneficiário: Mario Jose Abdalla Saad
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 20/06397-3 - Investigação da senescência celular em roedores submetidos à Obesidade
• Beneficiário: Caio Jordão Teixeira
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado