Akkermansia deficiency and mucin depletion are implicated in intestinal barrier dysfunction as earlier event in the development of inflammation in interleukin-10-deficient mice
BackgroundDysbiosis and mucin depletion are related with intestinal barrier dysfunction and seems to be an early pathophysiological event in inflammatory bowel disease (IBD). The objective of this work is to study these parameters in the natural history of colitis in IL-10 deficient mice (IL-10−/−)....
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Frontiers Media S.A.
2023-01-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmicb.2022.1083884/full |
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| author | Beatriz López-Cauce Beatriz López-Cauce Beatriz López-Cauce Marta Puerto Marta Puerto Juan José García Manuel Ponce-Alonso Federico Becerra-Aparicio Rosa del Campo Isabel Peligros María J. Fernández-Aceñero Yésica Gómez-Navarro José M. Lara José Miranda-Bautista José Miranda-Bautista Ignacio Marín-Jiménez Ignacio Marín-Jiménez Rafael Bañares Rafael Bañares Rafael Bañares Luis Menchén Luis Menchén Luis Menchén |
| author_facet | Beatriz López-Cauce Beatriz López-Cauce Beatriz López-Cauce Marta Puerto Marta Puerto Juan José García Manuel Ponce-Alonso Federico Becerra-Aparicio Rosa del Campo Isabel Peligros María J. Fernández-Aceñero Yésica Gómez-Navarro José M. Lara José Miranda-Bautista José Miranda-Bautista Ignacio Marín-Jiménez Ignacio Marín-Jiménez Rafael Bañares Rafael Bañares Rafael Bañares Luis Menchén Luis Menchén Luis Menchén |
| author_sort | Beatriz López-Cauce |
| collection | DOAJ |
| description | BackgroundDysbiosis and mucin depletion are related with intestinal barrier dysfunction and seems to be an early pathophysiological event in inflammatory bowel disease (IBD). The objective of this work is to study these parameters in the natural history of colitis in IL-10 deficient mice (IL-10−/−).MethodsWild type (WT) and IL-10−/−. mice were followed until sacrifice at 3, 5, 10, 20, 57, and 70 weeks. Body weight, colonic weight/length ratio and in vivo intestinal permeability were registered. Expression of inflammatory and adhesion molecules in the colon was explored by qPCR as Mucin-2 (MUC-2) and molecules involved in goblet cell maturation Interleukin-18 (IL-18) and WAP Four-Disulfide Core Domain 2 (WFDC2), the endoplasmic reticulum stress markers X-box-binding protein (Xbp-1) and Reticulon-4B (RTN-4B). Bacterial composition in feces and colonic mucosa was determined by massive sequencing of the V3–V4 regions of 16S rDNA gene.ResultsIL-10-/- mice showed histological inflammation at weeks 20 and 57, but most notably the intestinal permeability was significantly higher from week 10. Concordantly, the number of goblet cells and expression of MUC-2, IL-18, WFDC2 and Xbp-1 were significantly lower in KO from week 10. Nevertheless, no significant differences were found in the mRNA expression of MUC-2 or Xbp-1 between both groups—derived colon organoids. Significant bacterial differences began at week 5, being the Akkermansia deficiency in KO the most relevant result.ConclusionGut microbiota alterations and mucin depletion are associated with early intestinal barrier dysfunction and precede overt gut inflammation in this animal model of IBD. |
| first_indexed | 2024-04-10T23:55:21Z |
| format | Article |
| id | doaj.art-27cefef42f32452d996f96407bc0bb67 |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-04-10T23:55:21Z |
| publishDate | 2023-01-01 |
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| series | Frontiers in Microbiology |
| spelling | doaj.art-27cefef42f32452d996f96407bc0bb672023-01-10T13:27:01ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2023-01-011310.3389/fmicb.2022.10838841083884Akkermansia deficiency and mucin depletion are implicated in intestinal barrier dysfunction as earlier event in the development of inflammation in interleukin-10-deficient miceBeatriz López-Cauce0Beatriz López-Cauce1Beatriz López-Cauce2Marta Puerto3Marta Puerto4Juan José García5Manuel Ponce-Alonso6Federico Becerra-Aparicio7Rosa del Campo8Isabel Peligros9María J. Fernández-Aceñero10Yésica Gómez-Navarro11José M. Lara12José Miranda-Bautista13José Miranda-Bautista14Ignacio Marín-Jiménez15Ignacio Marín-Jiménez16Rafael Bañares17Rafael Bañares18Rafael Bañares19Luis Menchén20Luis Menchén21Luis Menchén22Servicio de Aparato Digestivo, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, SpainCentro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, SpainDepartamento de Microbiología y Parasitología Facultad de Farmacia, Universidad Complutense, Madrid, SpainServicio de Aparato Digestivo, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, SpainCentro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, SpainDepartamento de Microbiología y Parasitología Facultad de Farmacia, Universidad Complutense, Madrid, SpainServicio de Microbiología, Hospital Ramón y Cajal, CIBERINFEC, IRYCIS, Madrid, SpainServicio de Microbiología, Hospital Ramón y Cajal, CIBERINFEC, IRYCIS, Madrid, SpainServicio de Microbiología, Hospital Ramón y Cajal, CIBERINFEC, IRYCIS, Madrid, SpainServicio de Anatomía Patológica, Hospital General Universitario Gregorio Marañón, Madrid, SpainServicio de Anatomía Patológica, Hospital General Universitario Gregorio Marañón, Madrid, SpainServicio de Anatomía Patológica, Hospital General Universitario Gregorio Marañón, Madrid, SpainServicio de Anatomía Patológica, Hospital General Universitario Gregorio Marañón, Madrid, SpainServicio de Aparato Digestivo, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, SpainCentro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, SpainServicio de Aparato Digestivo, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, SpainCentro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, SpainServicio de Aparato Digestivo, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, SpainCentro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, SpainDepartamento de Medicina, Facultad de Medicina, Universidad Complutense, Madrid, SpainServicio de Aparato Digestivo, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, SpainCentro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, SpainDepartamento de Medicina, Facultad de Medicina, Universidad Complutense, Madrid, SpainBackgroundDysbiosis and mucin depletion are related with intestinal barrier dysfunction and seems to be an early pathophysiological event in inflammatory bowel disease (IBD). The objective of this work is to study these parameters in the natural history of colitis in IL-10 deficient mice (IL-10−/−).MethodsWild type (WT) and IL-10−/−. mice were followed until sacrifice at 3, 5, 10, 20, 57, and 70 weeks. Body weight, colonic weight/length ratio and in vivo intestinal permeability were registered. Expression of inflammatory and adhesion molecules in the colon was explored by qPCR as Mucin-2 (MUC-2) and molecules involved in goblet cell maturation Interleukin-18 (IL-18) and WAP Four-Disulfide Core Domain 2 (WFDC2), the endoplasmic reticulum stress markers X-box-binding protein (Xbp-1) and Reticulon-4B (RTN-4B). Bacterial composition in feces and colonic mucosa was determined by massive sequencing of the V3–V4 regions of 16S rDNA gene.ResultsIL-10-/- mice showed histological inflammation at weeks 20 and 57, but most notably the intestinal permeability was significantly higher from week 10. Concordantly, the number of goblet cells and expression of MUC-2, IL-18, WFDC2 and Xbp-1 were significantly lower in KO from week 10. Nevertheless, no significant differences were found in the mRNA expression of MUC-2 or Xbp-1 between both groups—derived colon organoids. Significant bacterial differences began at week 5, being the Akkermansia deficiency in KO the most relevant result.ConclusionGut microbiota alterations and mucin depletion are associated with early intestinal barrier dysfunction and precede overt gut inflammation in this animal model of IBD.https://www.frontiersin.org/articles/10.3389/fmicb.2022.1083884/fullAkkermansia muciniphilagut microbiomemucinintestinal barrierinterleukin-10-deficient miceinflammatory bowel disease |
| spellingShingle | Beatriz López-Cauce Beatriz López-Cauce Beatriz López-Cauce Marta Puerto Marta Puerto Juan José García Manuel Ponce-Alonso Federico Becerra-Aparicio Rosa del Campo Isabel Peligros María J. Fernández-Aceñero Yésica Gómez-Navarro José M. Lara José Miranda-Bautista José Miranda-Bautista Ignacio Marín-Jiménez Ignacio Marín-Jiménez Rafael Bañares Rafael Bañares Rafael Bañares Luis Menchén Luis Menchén Luis Menchén Akkermansia deficiency and mucin depletion are implicated in intestinal barrier dysfunction as earlier event in the development of inflammation in interleukin-10-deficient mice Frontiers in Microbiology Akkermansia muciniphila gut microbiome mucin intestinal barrier interleukin-10-deficient mice inflammatory bowel disease |
| title | Akkermansia deficiency and mucin depletion are implicated in intestinal barrier dysfunction as earlier event in the development of inflammation in interleukin-10-deficient mice |
| title_full | Akkermansia deficiency and mucin depletion are implicated in intestinal barrier dysfunction as earlier event in the development of inflammation in interleukin-10-deficient mice |
| title_fullStr | Akkermansia deficiency and mucin depletion are implicated in intestinal barrier dysfunction as earlier event in the development of inflammation in interleukin-10-deficient mice |
| title_full_unstemmed | Akkermansia deficiency and mucin depletion are implicated in intestinal barrier dysfunction as earlier event in the development of inflammation in interleukin-10-deficient mice |
| title_short | Akkermansia deficiency and mucin depletion are implicated in intestinal barrier dysfunction as earlier event in the development of inflammation in interleukin-10-deficient mice |
| title_sort | akkermansia deficiency and mucin depletion are implicated in intestinal barrier dysfunction as earlier event in the development of inflammation in interleukin 10 deficient mice |
| topic | Akkermansia muciniphila gut microbiome mucin intestinal barrier interleukin-10-deficient mice inflammatory bowel disease |
| url | https://www.frontiersin.org/articles/10.3389/fmicb.2022.1083884/full |
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