Akkermansia muciniphila ameliorates the age-related decline in colonic mucus thickness and attenuates immune activation in accelerated aging Ercc1 −/Δ7 mice

Abstract Background The use of Akkermansia muciniphila as potential therapeutic intervention is receiving increasing attention. Health benefits attributed to this bacterium include an improvement of metabolic disorders and exerting anti-inflammatory effects. The abundance of A. muciniphila is associ...

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Main Authors: Benthe van der Lugt, Adriaan A. van Beek, Steven Aalvink, Ben Meijer, Bruno Sovran, Wilbert P. Vermeij, Renata M. C. Brandt, Willem M. de Vos, Huub F. J. Savelkoul, Wilma T. Steegenga, Clara Belzer
Format: Article
Language:English
Published: BMC 2019-03-01
Series:Immunity & Ageing
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Online Access:http://link.springer.com/article/10.1186/s12979-019-0145-z
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spelling doaj-2009f81821734aafbf450b1122f78a112020-11-25T00:07:14ZengBMCImmunity & Ageing1742-49332019-03-0116111710.1186/s12979-019-0145-zAkkermansia muciniphila ameliorates the age-related decline in colonic mucus thickness and attenuates immune activation in accelerated aging Ercc1 −/Δ7 miceBenthe van der Lugt0Adriaan A. van Beek1Steven Aalvink2Ben Meijer3Bruno Sovran4Wilbert P. Vermeij5Renata M. C. Brandt6Willem M. de Vos7Huub F. J. Savelkoul8Wilma T. Steegenga9Clara Belzer10Division of Human Nutrition and Health, Wageningen University and ResearchDepartment of Immunology, Erasmus University Medical CenterLaboratory of Microbiology, Wageningen University and ResearchCell Biology and Immunology Group, Wageningen University and ResearchHost Microbe Interactomics, Wageningen University and ResearchDepartment of Molecular Genetics, Erasmus University Medical CenterDepartment of Molecular Genetics, Erasmus University Medical CenterLaboratory of Microbiology, Wageningen University and ResearchCell Biology and Immunology Group, Wageningen University and ResearchDivision of Human Nutrition and Health, Wageningen University and ResearchLaboratory of Microbiology, Wageningen University and ResearchAbstract Background The use of Akkermansia muciniphila as potential therapeutic intervention is receiving increasing attention. Health benefits attributed to this bacterium include an improvement of metabolic disorders and exerting anti-inflammatory effects. The abundance of A. muciniphila is associated with a healthy gut in early mid- and later life. However, the effects of A. muciniphila on a decline in intestinal health during the aging process are not investigated yet. We supplemented accelerated aging Ercc1 −/Δ7 mice with A. muciniphila for 10 weeks and investigated histological, transcriptional and immunological aspects of intestinal health. Results The thickness of the colonic mucus layer increased about 3-fold after long-term A. muciniphila supplementation and was even significantly thicker compared to mice supplemented with Lactobacillus plantarum WCFS1. Colonic gene expression profiles pointed towards a decreased expression of genes and pathways related to inflammation and immune function, and suggested a decreased presence of B cells in colon. Total B cell frequencies in spleen and mesenteric lymph nodes were not altered after A. muciniphila supplementation. Mature and immature B cell frequencies in bone marrow were increased, whereas B cell precursors were unaffected. These findings implicate that B cell migration rather than production was affected by A. muciniphila supplementation. Gene expression profiles in ileum pointed toward a decrease in metabolic- and immune-related processes and antimicrobial peptide production after A. muciniphila supplementation. Besides, A. muciniphila decreased the frequency of activated CD80+CD273− B cells in Peyer’s patches. Additionally, the increased numbers of peritoneal resident macrophages and a decrease in Ly6Cint monocyte frequencies in spleen and mesenteric lymph nodes add evidence for the potentially anti-inflammatory properties of A. muciniphila. Conclusions Altogether, we show that supplementation with A. muciniphila prevented the age-related decline in thickness of the colonic mucus layer and attenuated inflammation and immune-related processes at old age. This study implies that A. muciniphila supplementation can contribute to a promotion of healthy aging.http://link.springer.com/article/10.1186/s12979-019-0145-zAgingAkkermansia muciniphilaIntestinal immunityMucus layerIntestinal barrier
collection DOAJ
language English
format Article
sources DOAJ
author Benthe van der Lugt
Adriaan A. van Beek
Steven Aalvink
Ben Meijer
Bruno Sovran
Wilbert P. Vermeij
Renata M. C. Brandt
Willem M. de Vos
Huub F. J. Savelkoul
Wilma T. Steegenga
Clara Belzer
spellingShingle Benthe van der Lugt
Adriaan A. van Beek
Steven Aalvink
Ben Meijer
Bruno Sovran
Wilbert P. Vermeij
Renata M. C. Brandt
Willem M. de Vos
Huub F. J. Savelkoul
Wilma T. Steegenga
Clara Belzer
Akkermansia muciniphila ameliorates the age-related decline in colonic mucus thickness and attenuates immune activation in accelerated aging Ercc1 −/Δ7 mice
Immunity & Ageing
Aging
Akkermansia muciniphila
Intestinal immunity
Mucus layer
Intestinal barrier
author_facet Benthe van der Lugt
Adriaan A. van Beek
Steven Aalvink
Ben Meijer
Bruno Sovran
Wilbert P. Vermeij
Renata M. C. Brandt
Willem M. de Vos
Huub F. J. Savelkoul
Wilma T. Steegenga
Clara Belzer
author_sort Benthe van der Lugt
title Akkermansia muciniphila ameliorates the age-related decline in colonic mucus thickness and attenuates immune activation in accelerated aging Ercc1 −/Δ7 mice
title_short Akkermansia muciniphila ameliorates the age-related decline in colonic mucus thickness and attenuates immune activation in accelerated aging Ercc1 −/Δ7 mice
title_full Akkermansia muciniphila ameliorates the age-related decline in colonic mucus thickness and attenuates immune activation in accelerated aging Ercc1 −/Δ7 mice
title_fullStr Akkermansia muciniphila ameliorates the age-related decline in colonic mucus thickness and attenuates immune activation in accelerated aging Ercc1 −/Δ7 mice
title_full_unstemmed Akkermansia muciniphila ameliorates the age-related decline in colonic mucus thickness and attenuates immune activation in accelerated aging Ercc1 −/Δ7 mice
title_sort akkermansia muciniphila ameliorates the age-related decline in colonic mucus thickness and attenuates immune activation in accelerated aging ercc1 −/δ7 mice
publisher BMC
series Immunity & Ageing
issn 1742-4933
publishDate 2019-03-01
description Abstract Background The use of Akkermansia muciniphila as potential therapeutic intervention is receiving increasing attention. Health benefits attributed to this bacterium include an improvement of metabolic disorders and exerting anti-inflammatory effects. The abundance of A. muciniphila is associated with a healthy gut in early mid- and later life. However, the effects of A. muciniphila on a decline in intestinal health during the aging process are not investigated yet. We supplemented accelerated aging Ercc1 −/Δ7 mice with A. muciniphila for 10 weeks and investigated histological, transcriptional and immunological aspects of intestinal health. Results The thickness of the colonic mucus layer increased about 3-fold after long-term A. muciniphila supplementation and was even significantly thicker compared to mice supplemented with Lactobacillus plantarum WCFS1. Colonic gene expression profiles pointed towards a decreased expression of genes and pathways related to inflammation and immune function, and suggested a decreased presence of B cells in colon. Total B cell frequencies in spleen and mesenteric lymph nodes were not altered after A. muciniphila supplementation. Mature and immature B cell frequencies in bone marrow were increased, whereas B cell precursors were unaffected. These findings implicate that B cell migration rather than production was affected by A. muciniphila supplementation. Gene expression profiles in ileum pointed toward a decrease in metabolic- and immune-related processes and antimicrobial peptide production after A. muciniphila supplementation. Besides, A. muciniphila decreased the frequency of activated CD80+CD273− B cells in Peyer’s patches. Additionally, the increased numbers of peritoneal resident macrophages and a decrease in Ly6Cint monocyte frequencies in spleen and mesenteric lymph nodes add evidence for the potentially anti-inflammatory properties of A. muciniphila. Conclusions Altogether, we show that supplementation with A. muciniphila prevented the age-related decline in thickness of the colonic mucus layer and attenuated inflammation and immune-related processes at old age. This study implies that A. muciniphila supplementation can contribute to a promotion of healthy aging.
topic Aging
Akkermansia muciniphila
Intestinal immunity
Mucus layer
Intestinal barrier
url http://link.springer.com/article/10.1186/s12979-019-0145-z
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