Butyrate reduces adherent-invasive E. coli-evoked disruption of epithelial mitochondrial morphology and barrier function: involvement of free fatty acid receptor 3
ABSTRACTGut bacteria provide benefits to the host and have been implicated in inflammatory bowel disease (IBD), where adherent-invasive E. coli (AIEC) pathobionts (e.g., strain LF82) are associated with Crohn’s disease. E. coli-LF82 causes fragmentation of the epithelial mitochondrial network, leadi...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Taylor & Francis Group
2023-12-01
|
| Series: | Gut Microbes |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/19490976.2023.2281011 |
| _version_ | 1797320548030611456 |
|---|---|
| author | Samira A. Hamed Armaan Mohan Saranya Navaneetha Krishnan Arthur Wang Marija Drikic Nicole L. Prince Ian A. Lewis Jane Shearer Åsa V. Keita Johan D. Söderholm Timothy E. Shutt Derek M. McKay |
| author_facet | Samira A. Hamed Armaan Mohan Saranya Navaneetha Krishnan Arthur Wang Marija Drikic Nicole L. Prince Ian A. Lewis Jane Shearer Åsa V. Keita Johan D. Söderholm Timothy E. Shutt Derek M. McKay |
| author_sort | Samira A. Hamed |
| collection | DOAJ |
| description | ABSTRACTGut bacteria provide benefits to the host and have been implicated in inflammatory bowel disease (IBD), where adherent-invasive E. coli (AIEC) pathobionts (e.g., strain LF82) are associated with Crohn’s disease. E. coli-LF82 causes fragmentation of the epithelial mitochondrial network, leading to increased epithelial permeability. We hypothesized that butyrate would limit the epithelial mitochondrial disruption caused by E. coli-LF82. Human colonic organoids and the T84 epithelial cell line infected with E. coli-LF82 (MOI = 100, 4 h) showed a significant increase in mitochondrial network fission that was reduced by butyrate (10 mM) co-treatment. Butyrate reduced the loss of mitochondrial membrane potential caused by E. coli-LF82 and increased expression of PGC-1[Formula: see text] mRNA, the master regulator of mitochondrial biogenesis. Metabolomics revealed that butyrate significantly altered E. coli-LF82 central carbon metabolism leading to diminished glucose uptake and increased succinate secretion. Correlating with preservation of mitochondrial network form/function, butyrate reduced E. coli-LF82 transcytosis across T84-cell monolayers. The use of the G-protein inhibitor, pertussis toxin, implicated GPCR signaling as critical to the effect of butyrate, and the free fatty acid receptor three (FFAR3, GPR41) agonist, AR420626, reproduced butyrate’s effect in terms of ameliorating the loss of barrier function and reducing the mitochondrial fragmentation observed in E. coli-LF82 infected T84-cells and organoids. These data indicate that butyrate helps maintain epithelial mitochondrial form/function when challenged by E. coli-LF82 and that this occurs, at least in part, via FFAR3. Thus, loss of butyrate-producing bacteria in IBD in the context of pathobionts would contribute to loss of epithelial mitochondrial and barrier functions that could evoke disease and/or exaggerate a low-grade inflammation. |
| first_indexed | 2024-03-08T04:40:45Z |
| format | Article |
| id | doaj.art-4210087e373c4f0c8ae7f8feeb913bb8 |
| institution | Directory Open Access Journal |
| issn | 1949-0976 1949-0984 |
| language | English |
| last_indexed | 2024-03-08T04:40:45Z |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Gut Microbes |
| spelling | doaj.art-4210087e373c4f0c8ae7f8feeb913bb82024-02-08T12:02:08ZengTaylor & Francis GroupGut Microbes1949-09761949-09842023-12-0115210.1080/19490976.2023.2281011Butyrate reduces adherent-invasive E. coli-evoked disruption of epithelial mitochondrial morphology and barrier function: involvement of free fatty acid receptor 3Samira A. Hamed0Armaan Mohan1Saranya Navaneetha Krishnan2Arthur Wang3Marija Drikic4Nicole L. Prince5Ian A. Lewis6Jane Shearer7Åsa V. Keita8Johan D. Söderholm9Timothy E. Shutt10Derek M. McKay11Gastrointestinal Research Group, Inflammation Research Network, Host-Parasite Interactions Program, Department of Physiology & Pharmacology, Calvin, Phoebe and Joan Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, CanadaDepartments of Medical Genetics and Biochemistry & Molecular Biology, Alberta Children’s Hospital Research Institute, Hotchkiss Brain Institute, Snyder Institute, Cumming School of Medicine, University of Calgary, Calgary, CanadaGastrointestinal Research Group, Inflammation Research Network, Host-Parasite Interactions Program, Department of Physiology & Pharmacology, Calvin, Phoebe and Joan Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, CanadaGastrointestinal Research Group, Inflammation Research Network, Host-Parasite Interactions Program, Department of Physiology & Pharmacology, Calvin, Phoebe and Joan Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, CanadaCalgary Metabolomics Research Facility, Department of Biological Sciences, Faculty of Science, University of Calgary, Calgary, CanadaGastrointestinal Research Group, Inflammation Research Network, Host-Parasite Interactions Program, Department of Physiology & Pharmacology, Calvin, Phoebe and Joan Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, CanadaCalgary Metabolomics Research Facility, Department of Biological Sciences, Faculty of Science, University of Calgary, Calgary, CanadaDepartment of Biochemistry and Molecular Biology, Faculty of Kinesiology, University of Calgary, Calgary, CanadaDepartment of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology, Linköping University, Linköping, SwedenDepartment of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology, Linköping University, Linköping, SwedenDepartments of Medical Genetics and Biochemistry & Molecular Biology, Alberta Children’s Hospital Research Institute, Hotchkiss Brain Institute, Snyder Institute, Cumming School of Medicine, University of Calgary, Calgary, CanadaGastrointestinal Research Group, Inflammation Research Network, Host-Parasite Interactions Program, Department of Physiology & Pharmacology, Calvin, Phoebe and Joan Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, CanadaABSTRACTGut bacteria provide benefits to the host and have been implicated in inflammatory bowel disease (IBD), where adherent-invasive E. coli (AIEC) pathobionts (e.g., strain LF82) are associated with Crohn’s disease. E. coli-LF82 causes fragmentation of the epithelial mitochondrial network, leading to increased epithelial permeability. We hypothesized that butyrate would limit the epithelial mitochondrial disruption caused by E. coli-LF82. Human colonic organoids and the T84 epithelial cell line infected with E. coli-LF82 (MOI = 100, 4 h) showed a significant increase in mitochondrial network fission that was reduced by butyrate (10 mM) co-treatment. Butyrate reduced the loss of mitochondrial membrane potential caused by E. coli-LF82 and increased expression of PGC-1[Formula: see text] mRNA, the master regulator of mitochondrial biogenesis. Metabolomics revealed that butyrate significantly altered E. coli-LF82 central carbon metabolism leading to diminished glucose uptake and increased succinate secretion. Correlating with preservation of mitochondrial network form/function, butyrate reduced E. coli-LF82 transcytosis across T84-cell monolayers. The use of the G-protein inhibitor, pertussis toxin, implicated GPCR signaling as critical to the effect of butyrate, and the free fatty acid receptor three (FFAR3, GPR41) agonist, AR420626, reproduced butyrate’s effect in terms of ameliorating the loss of barrier function and reducing the mitochondrial fragmentation observed in E. coli-LF82 infected T84-cells and organoids. These data indicate that butyrate helps maintain epithelial mitochondrial form/function when challenged by E. coli-LF82 and that this occurs, at least in part, via FFAR3. Thus, loss of butyrate-producing bacteria in IBD in the context of pathobionts would contribute to loss of epithelial mitochondrial and barrier functions that could evoke disease and/or exaggerate a low-grade inflammation.https://www.tandfonline.com/doi/10.1080/19490976.2023.2281011Pathobiontmitochondrial dynamicsgut epitheliumorganoidT84 cellspermeability |
| spellingShingle | Samira A. Hamed Armaan Mohan Saranya Navaneetha Krishnan Arthur Wang Marija Drikic Nicole L. Prince Ian A. Lewis Jane Shearer Åsa V. Keita Johan D. Söderholm Timothy E. Shutt Derek M. McKay Butyrate reduces adherent-invasive E. coli-evoked disruption of epithelial mitochondrial morphology and barrier function: involvement of free fatty acid receptor 3 Gut Microbes Pathobiont mitochondrial dynamics gut epithelium organoid T84 cells permeability |
| title | Butyrate reduces adherent-invasive E. coli-evoked disruption of epithelial mitochondrial morphology and barrier function: involvement of free fatty acid receptor 3 |
| title_full | Butyrate reduces adherent-invasive E. coli-evoked disruption of epithelial mitochondrial morphology and barrier function: involvement of free fatty acid receptor 3 |
| title_fullStr | Butyrate reduces adherent-invasive E. coli-evoked disruption of epithelial mitochondrial morphology and barrier function: involvement of free fatty acid receptor 3 |
| title_full_unstemmed | Butyrate reduces adherent-invasive E. coli-evoked disruption of epithelial mitochondrial morphology and barrier function: involvement of free fatty acid receptor 3 |
| title_short | Butyrate reduces adherent-invasive E. coli-evoked disruption of epithelial mitochondrial morphology and barrier function: involvement of free fatty acid receptor 3 |
| title_sort | butyrate reduces adherent invasive e coli evoked disruption of epithelial mitochondrial morphology and barrier function involvement of free fatty acid receptor 3 |
| topic | Pathobiont mitochondrial dynamics gut epithelium organoid T84 cells permeability |
| url | https://www.tandfonline.com/doi/10.1080/19490976.2023.2281011 |
| work_keys_str_mv | AT samiraahamed butyratereducesadherentinvasiveecolievokeddisruptionofepithelialmitochondrialmorphologyandbarrierfunctioninvolvementoffreefattyacidreceptor3 AT armaanmohan butyratereducesadherentinvasiveecolievokeddisruptionofepithelialmitochondrialmorphologyandbarrierfunctioninvolvementoffreefattyacidreceptor3 AT saranyanavaneethakrishnan butyratereducesadherentinvasiveecolievokeddisruptionofepithelialmitochondrialmorphologyandbarrierfunctioninvolvementoffreefattyacidreceptor3 AT arthurwang butyratereducesadherentinvasiveecolievokeddisruptionofepithelialmitochondrialmorphologyandbarrierfunctioninvolvementoffreefattyacidreceptor3 AT marijadrikic butyratereducesadherentinvasiveecolievokeddisruptionofepithelialmitochondrialmorphologyandbarrierfunctioninvolvementoffreefattyacidreceptor3 AT nicolelprince butyratereducesadherentinvasiveecolievokeddisruptionofepithelialmitochondrialmorphologyandbarrierfunctioninvolvementoffreefattyacidreceptor3 AT ianalewis butyratereducesadherentinvasiveecolievokeddisruptionofepithelialmitochondrialmorphologyandbarrierfunctioninvolvementoffreefattyacidreceptor3 AT janeshearer butyratereducesadherentinvasiveecolievokeddisruptionofepithelialmitochondrialmorphologyandbarrierfunctioninvolvementoffreefattyacidreceptor3 AT asavkeita butyratereducesadherentinvasiveecolievokeddisruptionofepithelialmitochondrialmorphologyandbarrierfunctioninvolvementoffreefattyacidreceptor3 AT johandsoderholm butyratereducesadherentinvasiveecolievokeddisruptionofepithelialmitochondrialmorphologyandbarrierfunctioninvolvementoffreefattyacidreceptor3 AT timothyeshutt butyratereducesadherentinvasiveecolievokeddisruptionofepithelialmitochondrialmorphologyandbarrierfunctioninvolvementoffreefattyacidreceptor3 AT derekmmckay butyratereducesadherentinvasiveecolievokeddisruptionofepithelialmitochondrialmorphologyandbarrierfunctioninvolvementoffreefattyacidreceptor3 |