Proton Pump Inhibitor Pantoprazole Modulates Intestinal Microbiota and Induces TLR4 Signaling and Fibrosis in Mouse Liver
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...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-11-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/23/22/13766 |
| _version_ | 1797465143217487872 |
|---|---|
| author | Heloisa B. Assalin Kelly Cristiane Gabriel De Almeida Dioze Guadagnini Andrey Santos Caio J. Teixeira Silvana Bordin Guilherme Z. Rocha Mario J. A. Saad |
| author_facet | Heloisa B. Assalin Kelly Cristiane Gabriel De Almeida Dioze Guadagnini Andrey Santos Caio J. Teixeira Silvana Bordin Guilherme Z. Rocha Mario J. A. Saad |
| author_sort | Heloisa B. Assalin |
| collection | DOAJ |
| description | 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 TGFβ 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. |
| first_indexed | 2024-03-09T18:18:16Z |
| format | Article |
| id | doaj.art-0f34093903454ded8a5c2826b43f796d |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T18:18:16Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-0f34093903454ded8a5c2826b43f796d2023-11-24T08:33:03ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-11-0123221376610.3390/ijms232213766Proton Pump Inhibitor Pantoprazole Modulates Intestinal Microbiota and Induces TLR4 Signaling and Fibrosis in Mouse LiverHeloisa B. Assalin0Kelly Cristiane Gabriel De Almeida1Dioze Guadagnini2Andrey Santos3Caio J. Teixeira4Silvana Bordin5Guilherme Z. Rocha6Mario J. A. Saad7Department of Internal Medicine, School of Medical Sciences, University of Campinas, Campinas 13080-655, SP, BrazilDepartment of Internal Medicine, School of Medical Sciences, University of Campinas, Campinas 13080-655, SP, BrazilDepartment of Internal Medicine, School of Medical Sciences, University of Campinas, Campinas 13080-655, SP, BrazilDepartment of Internal Medicine, School of Medical Sciences, University of Campinas, Campinas 13080-655, SP, BrazilDepartment of Physiology and Biophysics, Institute of Biomedical Science, University of Sao Paulo, Sao Paulo 05508-000, SP, BrazilDepartment of Physiology and Biophysics, Institute of Biomedical Science, University of Sao Paulo, Sao Paulo 05508-000, SP, BrazilDepartment of Internal Medicine, School of Medical Sciences, University of Campinas, Campinas 13080-655, SP, BrazilDepartment of Internal Medicine, School of Medical Sciences, University of Campinas, Campinas 13080-655, SP, BrazilProton 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 TGFβ 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.https://www.mdpi.com/1422-0067/23/22/13766microbiotaproton pump inhibitorsliver steatosis |
| spellingShingle | Heloisa B. Assalin Kelly Cristiane Gabriel De Almeida Dioze Guadagnini Andrey Santos Caio J. Teixeira Silvana Bordin Guilherme Z. Rocha Mario J. A. Saad Proton Pump Inhibitor Pantoprazole Modulates Intestinal Microbiota and Induces TLR4 Signaling and Fibrosis in Mouse Liver International Journal of Molecular Sciences microbiota proton pump inhibitors liver steatosis |
| title | Proton Pump Inhibitor Pantoprazole Modulates Intestinal Microbiota and Induces TLR4 Signaling and Fibrosis in Mouse Liver |
| title_full | Proton Pump Inhibitor Pantoprazole Modulates Intestinal Microbiota and Induces TLR4 Signaling and Fibrosis in Mouse Liver |
| title_fullStr | Proton Pump Inhibitor Pantoprazole Modulates Intestinal Microbiota and Induces TLR4 Signaling and Fibrosis in Mouse Liver |
| title_full_unstemmed | Proton Pump Inhibitor Pantoprazole Modulates Intestinal Microbiota and Induces TLR4 Signaling and Fibrosis in Mouse Liver |
| title_short | Proton Pump Inhibitor Pantoprazole Modulates Intestinal Microbiota and Induces TLR4 Signaling and Fibrosis in Mouse Liver |
| title_sort | proton pump inhibitor pantoprazole modulates intestinal microbiota and induces tlr4 signaling and fibrosis in mouse liver |
| topic | microbiota proton pump inhibitors liver steatosis |
| url | https://www.mdpi.com/1422-0067/23/22/13766 |
| work_keys_str_mv | AT heloisabassalin protonpumpinhibitorpantoprazolemodulatesintestinalmicrobiotaandinducestlr4signalingandfibrosisinmouseliver AT kellycristianegabrieldealmeida protonpumpinhibitorpantoprazolemodulatesintestinalmicrobiotaandinducestlr4signalingandfibrosisinmouseliver AT diozeguadagnini protonpumpinhibitorpantoprazolemodulatesintestinalmicrobiotaandinducestlr4signalingandfibrosisinmouseliver AT andreysantos protonpumpinhibitorpantoprazolemodulatesintestinalmicrobiotaandinducestlr4signalingandfibrosisinmouseliver AT caiojteixeira protonpumpinhibitorpantoprazolemodulatesintestinalmicrobiotaandinducestlr4signalingandfibrosisinmouseliver AT silvanabordin protonpumpinhibitorpantoprazolemodulatesintestinalmicrobiotaandinducestlr4signalingandfibrosisinmouseliver AT guilhermezrocha protonpumpinhibitorpantoprazolemodulatesintestinalmicrobiotaandinducestlr4signalingandfibrosisinmouseliver AT mariojasaad protonpumpinhibitorpantoprazolemodulatesintestinalmicrobiotaandinducestlr4signalingandfibrosisinmouseliver |