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

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

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

3 Citations (Scopus)

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 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.

Original languageEnglish
Article number6
JournalImmunity and Ageing
Volume16
Issue number1
DOIs
Publication statusPublished - 8 Mar 2019

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Mucus
B-Lymphocytes
B-Lymphoid Precursor Cells
Transcriptome
Anti-Inflammatory Agents
Spleen
Lymph Nodes
Inflammation
Lactobacillus plantarum
Peyer's Patches
Health
Peritoneal Macrophages
Insurance Benefits
Ileum
Cell Movement
Monocytes
Colon
Bone Marrow
Bacteria
Gene Expression

Keywords

  • Aging
  • Akkermansia muciniphila
  • Intestinal barrier
  • Intestinal immunity
  • Mucus layer

Cite this

@article{994bb159164c42faa780b9aa5c3def40,
title = "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 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.",
keywords = "Aging, Akkermansia muciniphila, Intestinal barrier, Intestinal immunity, Mucus layer",
author = "{van der Lugt}, Benthe and {van Beek}, {Adriaan A.} and Steven Aalvink and Ben Meijer and Bruno Sovran and Vermeij, {Wilbert P.} and Brandt, {Renata M.C.} and {de Vos}, {Willem M.} and Savelkoul, {Huub F.J.} and Steegenga, {Wilma T.} and Clara Belzer",
year = "2019",
month = "3",
day = "8",
doi = "10.1186/s12979-019-0145-z",
language = "English",
volume = "16",
journal = "Immunity and Ageing",
issn = "1742-4933",
publisher = "BioMed Central",
number = "1",

}

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.

In: Immunity and Ageing, Vol. 16, No. 1, 6, 08.03.2019.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Akkermansia muciniphila ameliorates the age-related decline in colonic mucus thickness and attenuates immune activation in accelerated aging Ercc1 -/Δ7 mice

AU - van der Lugt, Benthe

AU - van Beek, Adriaan A.

AU - Aalvink, Steven

AU - Meijer, Ben

AU - Sovran, Bruno

AU - Vermeij, Wilbert P.

AU - Brandt, Renata M.C.

AU - de Vos, Willem M.

AU - Savelkoul, Huub F.J.

AU - Steegenga, Wilma T.

AU - Belzer, Clara

PY - 2019/3/8

Y1 - 2019/3/8

N2 - 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.

AB - 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.

KW - Aging

KW - Akkermansia muciniphila

KW - Intestinal barrier

KW - Intestinal immunity

KW - Mucus layer

U2 - 10.1186/s12979-019-0145-z

DO - 10.1186/s12979-019-0145-z

M3 - Article

VL - 16

JO - Immunity and Ageing

JF - Immunity and Ageing

SN - 1742-4933

IS - 1

M1 - 6

ER -