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Intestinal Osteopontin Protects From Alcohol-induced Liver Injury by Preserving the Gut Microbiome and the Intestinal Barrier Function
BACKGROUND & AIMS: The gut-liver axis plays a key role in the pathogenesis of alcohol-associated liver disease (ALD). We demonstrated that Opn(-/-) develop worse ALD than wild-type (WT) mice; however, the role of intestinal osteopontin (OPN) in ALD remains unknown. We hypothesized that overexpre...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9425038/ https://www.ncbi.nlm.nih.gov/pubmed/35811073 http://dx.doi.org/10.1016/j.jcmgh.2022.06.012 |
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author | Das, Sukanta Song, Zhuolun Han, Hui Ge, Xiaodong Desert, Romain Athavale, Dipti Babu Komakula, Sai Santosh Magdaleno, Fernando Chen, Wei Lantvit, Daniel Guzman, Grace Nieto, Natalia |
author_facet | Das, Sukanta Song, Zhuolun Han, Hui Ge, Xiaodong Desert, Romain Athavale, Dipti Babu Komakula, Sai Santosh Magdaleno, Fernando Chen, Wei Lantvit, Daniel Guzman, Grace Nieto, Natalia |
author_sort | Das, Sukanta |
collection | PubMed |
description | BACKGROUND & AIMS: The gut-liver axis plays a key role in the pathogenesis of alcohol-associated liver disease (ALD). We demonstrated that Opn(-/-) develop worse ALD than wild-type (WT) mice; however, the role of intestinal osteopontin (OPN) in ALD remains unknown. We hypothesized that overexpression of OPN in intestinal epithelial cells (IECs) could ameliorate ALD by preserving the gut microbiome and the intestinal barrier function. METHODS: Opn(KI IEC), Opn(ΔIEC), and WT mice were fed control or ethanol Lieber-DeCarli diet for 6 weeks. RESULTS: Opn(KI IEC) but not Opn(ΔIEC) mice showed improved intestinal barrier function and protection from ALD. There were less pathogenic and more beneficial bacteria in ethanol-fed Opn(KI IEC) than in WT mice. Fecal microbiome transplant (FMT) from Opn(KI IEC) to WT mice protected from ALD. FMT from ethanol-fed WT to Opn(KI IEC) mice failed to induce ALD. Antimicrobial peptides, Il33, pSTAT3, aryl hydrocarbon receptor (Ahr), and tight-junction protein expression were higher in IECs from jejunum of ethanol-fed Opn(KI IEC) than of WT mice. Ethanol-fed Opn(KI IEC) showed more tryptophan metabolites and short-chain fatty acids in portal serum than WT mice. FMT from Opn(KI IEC) to WT mice enhanced IECs Ahr and tight-junction protein expression. Oral administration of milk OPN replicated the protective effect of Opn(KI IEC) mice in ALD. CONCLUSION: Overexpression of OPN in IECs or administration of milk OPN maintain the intestinal microbiome by intestinal antimicrobial peptides. The increase in tryptophan metabolites and short-chain fatty acids signaling through the Ahr in IECs, preserve the intestinal barrier function and protect from ALD. |
format | Online Article Text |
id | pubmed-9425038 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-94250382022-08-31 Intestinal Osteopontin Protects From Alcohol-induced Liver Injury by Preserving the Gut Microbiome and the Intestinal Barrier Function Das, Sukanta Song, Zhuolun Han, Hui Ge, Xiaodong Desert, Romain Athavale, Dipti Babu Komakula, Sai Santosh Magdaleno, Fernando Chen, Wei Lantvit, Daniel Guzman, Grace Nieto, Natalia Cell Mol Gastroenterol Hepatol Original Research BACKGROUND & AIMS: The gut-liver axis plays a key role in the pathogenesis of alcohol-associated liver disease (ALD). We demonstrated that Opn(-/-) develop worse ALD than wild-type (WT) mice; however, the role of intestinal osteopontin (OPN) in ALD remains unknown. We hypothesized that overexpression of OPN in intestinal epithelial cells (IECs) could ameliorate ALD by preserving the gut microbiome and the intestinal barrier function. METHODS: Opn(KI IEC), Opn(ΔIEC), and WT mice were fed control or ethanol Lieber-DeCarli diet for 6 weeks. RESULTS: Opn(KI IEC) but not Opn(ΔIEC) mice showed improved intestinal barrier function and protection from ALD. There were less pathogenic and more beneficial bacteria in ethanol-fed Opn(KI IEC) than in WT mice. Fecal microbiome transplant (FMT) from Opn(KI IEC) to WT mice protected from ALD. FMT from ethanol-fed WT to Opn(KI IEC) mice failed to induce ALD. Antimicrobial peptides, Il33, pSTAT3, aryl hydrocarbon receptor (Ahr), and tight-junction protein expression were higher in IECs from jejunum of ethanol-fed Opn(KI IEC) than of WT mice. Ethanol-fed Opn(KI IEC) showed more tryptophan metabolites and short-chain fatty acids in portal serum than WT mice. FMT from Opn(KI IEC) to WT mice enhanced IECs Ahr and tight-junction protein expression. Oral administration of milk OPN replicated the protective effect of Opn(KI IEC) mice in ALD. CONCLUSION: Overexpression of OPN in IECs or administration of milk OPN maintain the intestinal microbiome by intestinal antimicrobial peptides. The increase in tryptophan metabolites and short-chain fatty acids signaling through the Ahr in IECs, preserve the intestinal barrier function and protect from ALD. Elsevier 2022-07-08 /pmc/articles/PMC9425038/ /pubmed/35811073 http://dx.doi.org/10.1016/j.jcmgh.2022.06.012 Text en © 2022 The Authors https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Original Research Das, Sukanta Song, Zhuolun Han, Hui Ge, Xiaodong Desert, Romain Athavale, Dipti Babu Komakula, Sai Santosh Magdaleno, Fernando Chen, Wei Lantvit, Daniel Guzman, Grace Nieto, Natalia Intestinal Osteopontin Protects From Alcohol-induced Liver Injury by Preserving the Gut Microbiome and the Intestinal Barrier Function |
title | Intestinal Osteopontin Protects From Alcohol-induced Liver Injury by Preserving the Gut Microbiome and the Intestinal Barrier Function |
title_full | Intestinal Osteopontin Protects From Alcohol-induced Liver Injury by Preserving the Gut Microbiome and the Intestinal Barrier Function |
title_fullStr | Intestinal Osteopontin Protects From Alcohol-induced Liver Injury by Preserving the Gut Microbiome and the Intestinal Barrier Function |
title_full_unstemmed | Intestinal Osteopontin Protects From Alcohol-induced Liver Injury by Preserving the Gut Microbiome and the Intestinal Barrier Function |
title_short | Intestinal Osteopontin Protects From Alcohol-induced Liver Injury by Preserving the Gut Microbiome and the Intestinal Barrier Function |
title_sort | intestinal osteopontin protects from alcohol-induced liver injury by preserving the gut microbiome and the intestinal barrier function |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9425038/ https://www.ncbi.nlm.nih.gov/pubmed/35811073 http://dx.doi.org/10.1016/j.jcmgh.2022.06.012 |
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