PMID- 36699599 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20230202 IS - 1664-302X (Print) IS - 1664-302X (Electronic) IS - 1664-302X (Linking) VI - 13 DP - 2022 TI - Akkermansia deficiency and mucin depletion are implicated in intestinal barrier dysfunction as earlier event in the development of inflammation in interleukin-10-deficient mice. PG - 1083884 LID - 10.3389/fmicb.2022.1083884 [doi] LID - 1083884 AB - BACKGROUND: Dysbiosis 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(-/-)). METHODS: Wild 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. RESULTS: IL-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. CONCLUSION: Gut microbiota alterations and mucin depletion are associated with early intestinal barrier dysfunction and precede overt gut inflammation in this animal model of IBD. CI - Copyright (c) 2023 Lopez-Cauce, Puerto, Garcia, Ponce-Alonso, Becerra-Aparicio, del Campo, Peligros, Fernandez-Acenero, Gomez-Navarro, Lara, Miranda-Bautista, Marin-Jimenez, Banares and Menchen. FAU - Lopez-Cauce, Beatriz AU - Lopez-Cauce B AD - Servicio de Aparato Digestivo, Hospital General Universitario Gregorio Maranon, Instituto de Investigacion Sanitaria Gregorio Maranon, Madrid, Spain. AD - Centro de Investigacion Biomedica en Red de Enfermedades Hepaticas y Digestivas (CIBEREHD), Madrid, Spain. AD - Departamento de Microbiologia y Parasitologia Facultad de Farmacia, Universidad Complutense, Madrid, Spain. FAU - Puerto, Marta AU - Puerto M AD - Servicio de Aparato Digestivo, Hospital General Universitario Gregorio Maranon, Instituto de Investigacion Sanitaria Gregorio Maranon, Madrid, Spain. AD - Centro de Investigacion Biomedica en Red de Enfermedades Hepaticas y Digestivas (CIBEREHD), Madrid, Spain. FAU - Garcia, Juan Jose AU - Garcia JJ AD - Departamento de Microbiologia y Parasitologia Facultad de Farmacia, Universidad Complutense, Madrid, Spain. FAU - Ponce-Alonso, Manuel AU - Ponce-Alonso M AD - Servicio de Microbiologia, Hospital Ramon y Cajal, CIBERINFEC, IRYCIS, Madrid, Spain. FAU - Becerra-Aparicio, Federico AU - Becerra-Aparicio F AD - Servicio de Microbiologia, Hospital Ramon y Cajal, CIBERINFEC, IRYCIS, Madrid, Spain. FAU - Del Campo, Rosa AU - Del Campo R AD - Servicio de Microbiologia, Hospital Ramon y Cajal, CIBERINFEC, IRYCIS, Madrid, Spain. FAU - Peligros, Isabel AU - Peligros I AD - Servicio de Anatomia Patologica, Hospital General Universitario Gregorio Maranon, Madrid, Spain. FAU - Fernandez-Acenero, Maria J AU - Fernandez-Acenero MJ AD - Servicio de Anatomia Patologica, Hospital General Universitario Gregorio Maranon, Madrid, Spain. FAU - Gomez-Navarro, Yesica AU - Gomez-Navarro Y AD - Servicio de Anatomia Patologica, Hospital General Universitario Gregorio Maranon, Madrid, Spain. FAU - Lara, Jose M AU - Lara JM AD - Servicio de Anatomia Patologica, Hospital General Universitario Gregorio Maranon, Madrid, Spain. FAU - Miranda-Bautista, Jose AU - Miranda-Bautista J AD - Servicio de Aparato Digestivo, Hospital General Universitario Gregorio Maranon, Instituto de Investigacion Sanitaria Gregorio Maranon, Madrid, Spain. AD - Centro de Investigacion Biomedica en Red de Enfermedades Hepaticas y Digestivas (CIBEREHD), Madrid, Spain. FAU - Marin-Jimenez, Ignacio AU - Marin-Jimenez I AD - Servicio de Aparato Digestivo, Hospital General Universitario Gregorio Maranon, Instituto de Investigacion Sanitaria Gregorio Maranon, Madrid, Spain. AD - Centro de Investigacion Biomedica en Red de Enfermedades Hepaticas y Digestivas (CIBEREHD), Madrid, Spain. FAU - Banares, Rafael AU - Banares R AD - Servicio de Aparato Digestivo, Hospital General Universitario Gregorio Maranon, Instituto de Investigacion Sanitaria Gregorio Maranon, Madrid, Spain. AD - Centro de Investigacion Biomedica en Red de Enfermedades Hepaticas y Digestivas (CIBEREHD), Madrid, Spain. AD - Departamento de Medicina, Facultad de Medicina, Universidad Complutense, Madrid, Spain. FAU - Menchen, Luis AU - Menchen L AD - Servicio de Aparato Digestivo, Hospital General Universitario Gregorio Maranon, Instituto de Investigacion Sanitaria Gregorio Maranon, Madrid, Spain. AD - Centro de Investigacion Biomedica en Red de Enfermedades Hepaticas y Digestivas (CIBEREHD), Madrid, Spain. AD - Departamento de Medicina, Facultad de Medicina, Universidad Complutense, Madrid, Spain. LA - eng PT - Journal Article DEP - 20230109 PL - Switzerland TA - Front Microbiol JT - Frontiers in microbiology JID - 101548977 PMC - PMC9869054 OTO - NOTNLM OT - Akkermansia muciniphila OT - gut microbiome OT - inflammatory bowel disease OT - interleukin-10-deficient mice OT - intestinal barrier OT - mucin COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2023/01/27 06:00 MHDA- 2023/01/27 06:01 PMCR- 2023/01/09 CRDT- 2023/01/26 02:47 PHST- 2022/10/31 00:00 [received] PHST- 2022/12/23 00:00 [accepted] PHST- 2023/01/26 02:47 [entrez] PHST- 2023/01/27 06:00 [pubmed] PHST- 2023/01/27 06:01 [medline] PHST- 2023/01/09 00:00 [pmc-release] AID - 10.3389/fmicb.2022.1083884 [doi] PST - epublish SO - Front Microbiol. 2023 Jan 9;13:1083884. doi: 10.3389/fmicb.2022.1083884. eCollection 2022.