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

Research output: Contribution to journalArticleAcademicpeer-review

2 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

Fingerprint

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 -