<i>Akkermansia muciniphila</i> Reduces Peritonitis and Improves Intestinal Tissue Wound Healing after a Colonic Transmural Defect by a MyD88-Dependent Mechanism
Anastomotic leakage is a major complication following colorectal surgery leading to peritonitis, complications, and mortality. <i>Akkermansia muciniphila</i> has shown beneficial effects on the gut barrier function. Whether <i>A. muciniphila</i> reduces peritonitis and mortal...
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MDPI AG
2022-08-01
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| Online Access: | https://www.mdpi.com/2073-4409/11/17/2666 |
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| author | Radu Bachmann Matthias Van Hul Pamela Baldin Daniel Léonard Nathalie M. Delzenne Clara Belzer Janneke P. Ouwerkerk Dirk Repsilber Ignacio Rangel Alex Kartheuser Robert Jan Brummer Willem M. De Vos Patrice D. Cani |
| author_facet | Radu Bachmann Matthias Van Hul Pamela Baldin Daniel Léonard Nathalie M. Delzenne Clara Belzer Janneke P. Ouwerkerk Dirk Repsilber Ignacio Rangel Alex Kartheuser Robert Jan Brummer Willem M. De Vos Patrice D. Cani |
| author_sort | Radu Bachmann |
| collection | DOAJ |
| description | Anastomotic leakage is a major complication following colorectal surgery leading to peritonitis, complications, and mortality. <i>Akkermansia muciniphila</i> has shown beneficial effects on the gut barrier function. Whether <i>A. muciniphila</i> reduces peritonitis and mortality during colonic leakage is unknown. Whether <i>A. muciniphila</i> can directly modulate the expression of genes in the colonic mucosa in humans has never been studied. We investigated the effects of a pretreatment (14 days) with live <i>A. muciniphila</i> prior to surgical colonic perforation on peritonitis, mortality, and wound healing. We used mice with an inducible intestinal-epithelial-cell-specific deletion of MyD88 (IEC-MyD88 KO) to investigate the role of the innate immune system in this context. In a proof-of-concept pilot study, healthy humans were exposed to <i>A. muciniphila</i> for 2 h and colonic biopsies taken before and after colonic instillation for transcriptomic analysis. Seven days after colonic perforation, <i>A.-muciniphila</i>-treated mice had significantly lower mortality and severity of peritonitis. This effect was associated with significant improvements of wound histological healing scores, higher production of IL22, but no changes in the mucus layer thickness or genes involved in cell renewal, proliferation, or differentiation. All these effects were abolished in IEC-MyD88 KO mice. Finally, human subjects exposed to <i>A. muciniphila</i> exhibited an increased level of the bacterium at the mucus level 2 h after instillation and significant changes in the expression of different genes involved in the regulation of cell cycling, gene transcription, immunity, and inflammation in their colonic mucosa. <i>A. muciniphila</i> improves wound healing during transmural colonic wall defect through mechanisms possibly involving IL22 signaling and requiring MyD88 in the intestinal cells. In healthy humans, colonic administration of <i>A. muciniphila</i> is well tolerated and changes the expression of genes involved in the immune pathways. |
| first_indexed | 2024-03-10T01:57:02Z |
| format | Article |
| id | doaj.art-9b01dcb48c2a48068fcce6134fe473cd |
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| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T01:57:02Z |
| publishDate | 2022-08-01 |
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| spelling | doaj.art-9b01dcb48c2a48068fcce6134fe473cd2023-11-23T12:54:54ZengMDPI AGCells2073-44092022-08-011117266610.3390/cells11172666<i>Akkermansia muciniphila</i> Reduces Peritonitis and Improves Intestinal Tissue Wound Healing after a Colonic Transmural Defect by a MyD88-Dependent MechanismRadu Bachmann0Matthias Van Hul1Pamela Baldin2Daniel Léonard3Nathalie M. Delzenne4Clara Belzer5Janneke P. Ouwerkerk6Dirk Repsilber7Ignacio Rangel8Alex Kartheuser9Robert Jan Brummer10Willem M. De Vos11Patrice D. Cani12Metabolism and Nutrition Research Group, Louvain Drug Research Institute, Walloon Excellence in Life Sciences and BIOtechnology (WELBIO), UCLouvain, Université Catholique de Louvain, 1200 Brussels, BelgiumMetabolism and Nutrition Research Group, Louvain Drug Research Institute, Walloon Excellence in Life Sciences and BIOtechnology (WELBIO), UCLouvain, Université Catholique de Louvain, 1200 Brussels, BelgiumPathology Department, Cliniques Universitaires Saint-Luc, UCLouvain, 1200 Brussels, BelgiumColorectal Surgery Unit, Cliniques Universitaires Saint-Luc, 1200 Brussels, BelgiumMetabolism and Nutrition Research Group, Louvain Drug Research Institute, Walloon Excellence in Life Sciences and BIOtechnology (WELBIO), UCLouvain, Université Catholique de Louvain, 1200 Brussels, BelgiumLaboratory of Microbiology, Wageningen University, 6700 EH Wageningen, The NetherlandsLaboratory of Microbiology, Wageningen University, 6700 EH Wageningen, The NetherlandsNutrition-Gut-Brain Interactions Research Centre, School of Medical Sciences, Faculty of Medicine and Health, Örebro University, S-701 82 Örebro, SwedenNutrition-Gut-Brain Interactions Research Centre, School of Medical Sciences, Faculty of Medicine and Health, Örebro University, S-701 82 Örebro, SwedenColorectal Surgery Unit, Cliniques Universitaires Saint-Luc, 1200 Brussels, BelgiumNutrition-Gut-Brain Interactions Research Centre, School of Medical Sciences, Faculty of Medicine and Health, Örebro University, S-701 82 Örebro, SwedenLaboratory of Microbiology, Wageningen University, 6700 EH Wageningen, The NetherlandsMetabolism and Nutrition Research Group, Louvain Drug Research Institute, Walloon Excellence in Life Sciences and BIOtechnology (WELBIO), UCLouvain, Université Catholique de Louvain, 1200 Brussels, BelgiumAnastomotic leakage is a major complication following colorectal surgery leading to peritonitis, complications, and mortality. <i>Akkermansia muciniphila</i> has shown beneficial effects on the gut barrier function. Whether <i>A. muciniphila</i> reduces peritonitis and mortality during colonic leakage is unknown. Whether <i>A. muciniphila</i> can directly modulate the expression of genes in the colonic mucosa in humans has never been studied. We investigated the effects of a pretreatment (14 days) with live <i>A. muciniphila</i> prior to surgical colonic perforation on peritonitis, mortality, and wound healing. We used mice with an inducible intestinal-epithelial-cell-specific deletion of MyD88 (IEC-MyD88 KO) to investigate the role of the innate immune system in this context. In a proof-of-concept pilot study, healthy humans were exposed to <i>A. muciniphila</i> for 2 h and colonic biopsies taken before and after colonic instillation for transcriptomic analysis. Seven days after colonic perforation, <i>A.-muciniphila</i>-treated mice had significantly lower mortality and severity of peritonitis. This effect was associated with significant improvements of wound histological healing scores, higher production of IL22, but no changes in the mucus layer thickness or genes involved in cell renewal, proliferation, or differentiation. All these effects were abolished in IEC-MyD88 KO mice. Finally, human subjects exposed to <i>A. muciniphila</i> exhibited an increased level of the bacterium at the mucus level 2 h after instillation and significant changes in the expression of different genes involved in the regulation of cell cycling, gene transcription, immunity, and inflammation in their colonic mucosa. <i>A. muciniphila</i> improves wound healing during transmural colonic wall defect through mechanisms possibly involving IL22 signaling and requiring MyD88 in the intestinal cells. In healthy humans, colonic administration of <i>A. muciniphila</i> is well tolerated and changes the expression of genes involved in the immune pathways.https://www.mdpi.com/2073-4409/11/17/2666<i>Akkermansia muciniphila</i>wound healingcolonic leakageperitonitisMyd88 |
| spellingShingle | Radu Bachmann Matthias Van Hul Pamela Baldin Daniel Léonard Nathalie M. Delzenne Clara Belzer Janneke P. Ouwerkerk Dirk Repsilber Ignacio Rangel Alex Kartheuser Robert Jan Brummer Willem M. De Vos Patrice D. Cani <i>Akkermansia muciniphila</i> Reduces Peritonitis and Improves Intestinal Tissue Wound Healing after a Colonic Transmural Defect by a MyD88-Dependent Mechanism Cells <i>Akkermansia muciniphila</i> wound healing colonic leakage peritonitis Myd88 |
| title | <i>Akkermansia muciniphila</i> Reduces Peritonitis and Improves Intestinal Tissue Wound Healing after a Colonic Transmural Defect by a MyD88-Dependent Mechanism |
| title_full | <i>Akkermansia muciniphila</i> Reduces Peritonitis and Improves Intestinal Tissue Wound Healing after a Colonic Transmural Defect by a MyD88-Dependent Mechanism |
| title_fullStr | <i>Akkermansia muciniphila</i> Reduces Peritonitis and Improves Intestinal Tissue Wound Healing after a Colonic Transmural Defect by a MyD88-Dependent Mechanism |
| title_full_unstemmed | <i>Akkermansia muciniphila</i> Reduces Peritonitis and Improves Intestinal Tissue Wound Healing after a Colonic Transmural Defect by a MyD88-Dependent Mechanism |
| title_short | <i>Akkermansia muciniphila</i> Reduces Peritonitis and Improves Intestinal Tissue Wound Healing after a Colonic Transmural Defect by a MyD88-Dependent Mechanism |
| title_sort | i akkermansia muciniphila i reduces peritonitis and improves intestinal tissue wound healing after a colonic transmural defect by a myd88 dependent mechanism |
| topic | <i>Akkermansia muciniphila</i> wound healing colonic leakage peritonitis Myd88 |
| url | https://www.mdpi.com/2073-4409/11/17/2666 |
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