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

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 wit...

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Autores principales: van der Lugt, Benthe, van Beek, Adriaan A., Aalvink, Steven, Meijer, Ben, Sovran, Bruno, Vermeij, Wilbert P., Brandt, Renata M. C., de Vos, Willem M., Savelkoul, Huub F. J., Steegenga, Wilma T., Belzer, Clara
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6408808/
https://www.ncbi.nlm.nih.gov/pubmed/30899315
http://dx.doi.org/10.1186/s12979-019-0145-z
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author van der Lugt, Benthe
van Beek, Adriaan A.
Aalvink, Steven
Meijer, Ben
Sovran, Bruno
Vermeij, Wilbert P.
Brandt, Renata M. C.
de Vos, Willem M.
Savelkoul, Huub F. J.
Steegenga, Wilma T.
Belzer, Clara
author_facet van der Lugt, Benthe
van Beek, Adriaan A.
Aalvink, Steven
Meijer, Ben
Sovran, Bruno
Vermeij, Wilbert P.
Brandt, Renata M. C.
de Vos, Willem M.
Savelkoul, Huub F. J.
Steegenga, Wilma T.
Belzer, Clara
author_sort van der Lugt, Benthe
collection PubMed
description 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 Ly6C(int) 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12979-019-0145-z) contains supplementary material, which is available to authorized users.
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spelling pubmed-64088082019-03-21 Akkermansia muciniphila ameliorates the age-related decline in colonic mucus thickness and attenuates immune activation in accelerated aging Ercc1(−/Δ7) mice van der Lugt, Benthe van Beek, Adriaan A. Aalvink, Steven Meijer, Ben Sovran, Bruno Vermeij, Wilbert P. Brandt, Renata M. C. de Vos, Willem M. Savelkoul, Huub F. J. Steegenga, Wilma T. Belzer, Clara Immun Ageing Research 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 Ly6C(int) 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12979-019-0145-z) contains supplementary material, which is available to authorized users. BioMed Central 2019-03-08 /pmc/articles/PMC6408808/ /pubmed/30899315 http://dx.doi.org/10.1186/s12979-019-0145-z Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
van der Lugt, Benthe
van Beek, Adriaan A.
Aalvink, Steven
Meijer, Ben
Sovran, Bruno
Vermeij, Wilbert P.
Brandt, Renata M. C.
de Vos, Willem M.
Savelkoul, Huub F. J.
Steegenga, Wilma T.
Belzer, Clara
Akkermansia muciniphila ameliorates the age-related decline in colonic mucus thickness and attenuates immune activation in accelerated aging Ercc1(−/Δ7) mice
title 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_short 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
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6408808/
https://www.ncbi.nlm.nih.gov/pubmed/30899315
http://dx.doi.org/10.1186/s12979-019-0145-z
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