Aged gut microbiota contributes to systemical inflammaging after transfer to germ-free mice

Floris Fransen*, Adriaan A. van Beek, Theo Borghuis, Sahar El Aidy, Floor Hugenholtz, Christa van der Gaast - de Jongh, Huub F.J. Savelkoul, Marien I. de Jonge, Mark V. Boekschoten, Hauke Smidt, Marijke M. Faas, Paul de Vos

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

47 Citations (Scopus)

Abstract

Advanced age is associated with chronic low-grade inflammation, which is usually referred to as inflammaging. Elderly are also known to have an altered gut microbiota composition. However, whether inflammaging is a cause or consequence of an altered gut microbiota composition is not clear. In this study, gut microbiota from young or old conventional mice was transferred to young germ-free (GF) mice. Four weeks after gut microbiota transfer immune cell populations in spleen, Peyer's patches, and mesenteric lymph nodes from conventionalized GF mice were analyzed by flow cytometry. In addition, whole-genome gene expression in the ileum was analyzed by microarray. Gut microbiota composition of donor and recipient mice was analyzed with 16S rDNA sequencing. Here, we show by transferring aged microbiota to young GF mice that certain bacterial species within the aged microbiota promote inflammaging. This effect was associated with lower levels of Akkermansia and higher levels of TM7 bacteria and Proteobacteria in the aged microbiota after transfer. The aged microbiota promoted inflammation in the small intestine in the GF mice and enhanced leakage of inflammatory bacterial components into the circulation was observed. Moreover, the aged microbiota promoted increased T cell activation in the systemic compartment. In conclusion, these data indicate that the gut microbiota from old mice contributes to inflammaging after transfer to young GF mice.
Original languageEnglish
Article number1385
JournalFrontiers in Immunology
Volume8
DOIs
Publication statusPublished - 2 Nov 2017

Fingerprint

Microbiota
Inflammation
Proteobacteria
Peyer's Patches
Gastrointestinal Microbiome
Ribosomal DNA
Ileum
Small Intestine
Flow Cytometry
Spleen
Lymph Nodes
Tissue Donors
Genome
Bacteria
T-Lymphocytes
Gene Expression
Population

Keywords

  • Aging
  • Germ-free mice
  • Gut microbiome
  • Immune system
  • Inflammaging

Cite this

Fransen, F., van Beek, A. A., Borghuis, T., El Aidy, S., Hugenholtz, F., van der Gaast - de Jongh, C., ... de Vos, P. (2017). Aged gut microbiota contributes to systemical inflammaging after transfer to germ-free mice. Frontiers in Immunology, 8, [1385]. https://doi.org/10.3389/fimmu.2017.01385
Fransen, Floris ; van Beek, Adriaan A. ; Borghuis, Theo ; El Aidy, Sahar ; Hugenholtz, Floor ; van der Gaast - de Jongh, Christa ; Savelkoul, Huub F.J. ; de Jonge, Marien I. ; Boekschoten, Mark V. ; Smidt, Hauke ; Faas, Marijke M. ; de Vos, Paul. / Aged gut microbiota contributes to systemical inflammaging after transfer to germ-free mice. In: Frontiers in Immunology. 2017 ; Vol. 8.
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abstract = "Advanced age is associated with chronic low-grade inflammation, which is usually referred to as inflammaging. Elderly are also known to have an altered gut microbiota composition. However, whether inflammaging is a cause or consequence of an altered gut microbiota composition is not clear. In this study, gut microbiota from young or old conventional mice was transferred to young germ-free (GF) mice. Four weeks after gut microbiota transfer immune cell populations in spleen, Peyer's patches, and mesenteric lymph nodes from conventionalized GF mice were analyzed by flow cytometry. In addition, whole-genome gene expression in the ileum was analyzed by microarray. Gut microbiota composition of donor and recipient mice was analyzed with 16S rDNA sequencing. Here, we show by transferring aged microbiota to young GF mice that certain bacterial species within the aged microbiota promote inflammaging. This effect was associated with lower levels of Akkermansia and higher levels of TM7 bacteria and Proteobacteria in the aged microbiota after transfer. The aged microbiota promoted inflammation in the small intestine in the GF mice and enhanced leakage of inflammatory bacterial components into the circulation was observed. Moreover, the aged microbiota promoted increased T cell activation in the systemic compartment. In conclusion, these data indicate that the gut microbiota from old mice contributes to inflammaging after transfer to young GF mice.",
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author = "Floris Fransen and {van Beek}, {Adriaan A.} and Theo Borghuis and {El Aidy}, Sahar and Floor Hugenholtz and {van der Gaast - de Jongh}, Christa and Savelkoul, {Huub F.J.} and {de Jonge}, {Marien I.} and Boekschoten, {Mark V.} and Hauke Smidt and Faas, {Marijke M.} and {de Vos}, Paul",
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Fransen, F, van Beek, AA, Borghuis, T, El Aidy, S, Hugenholtz, F, van der Gaast - de Jongh, C, Savelkoul, HFJ, de Jonge, MI, Boekschoten, MV, Smidt, H, Faas, MM & de Vos, P 2017, 'Aged gut microbiota contributes to systemical inflammaging after transfer to germ-free mice', Frontiers in Immunology, vol. 8, 1385. https://doi.org/10.3389/fimmu.2017.01385

Aged gut microbiota contributes to systemical inflammaging after transfer to germ-free mice. / Fransen, Floris; van Beek, Adriaan A.; Borghuis, Theo; El Aidy, Sahar; Hugenholtz, Floor; van der Gaast - de Jongh, Christa; Savelkoul, Huub F.J.; de Jonge, Marien I.; Boekschoten, Mark V.; Smidt, Hauke; Faas, Marijke M.; de Vos, Paul.

In: Frontiers in Immunology, Vol. 8, 1385, 02.11.2017.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Aged gut microbiota contributes to systemical inflammaging after transfer to germ-free mice

AU - Fransen, Floris

AU - van Beek, Adriaan A.

AU - Borghuis, Theo

AU - El Aidy, Sahar

AU - Hugenholtz, Floor

AU - van der Gaast - de Jongh, Christa

AU - Savelkoul, Huub F.J.

AU - de Jonge, Marien I.

AU - Boekschoten, Mark V.

AU - Smidt, Hauke

AU - Faas, Marijke M.

AU - de Vos, Paul

PY - 2017/11/2

Y1 - 2017/11/2

N2 - Advanced age is associated with chronic low-grade inflammation, which is usually referred to as inflammaging. Elderly are also known to have an altered gut microbiota composition. However, whether inflammaging is a cause or consequence of an altered gut microbiota composition is not clear. In this study, gut microbiota from young or old conventional mice was transferred to young germ-free (GF) mice. Four weeks after gut microbiota transfer immune cell populations in spleen, Peyer's patches, and mesenteric lymph nodes from conventionalized GF mice were analyzed by flow cytometry. In addition, whole-genome gene expression in the ileum was analyzed by microarray. Gut microbiota composition of donor and recipient mice was analyzed with 16S rDNA sequencing. Here, we show by transferring aged microbiota to young GF mice that certain bacterial species within the aged microbiota promote inflammaging. This effect was associated with lower levels of Akkermansia and higher levels of TM7 bacteria and Proteobacteria in the aged microbiota after transfer. The aged microbiota promoted inflammation in the small intestine in the GF mice and enhanced leakage of inflammatory bacterial components into the circulation was observed. Moreover, the aged microbiota promoted increased T cell activation in the systemic compartment. In conclusion, these data indicate that the gut microbiota from old mice contributes to inflammaging after transfer to young GF mice.

AB - Advanced age is associated with chronic low-grade inflammation, which is usually referred to as inflammaging. Elderly are also known to have an altered gut microbiota composition. However, whether inflammaging is a cause or consequence of an altered gut microbiota composition is not clear. In this study, gut microbiota from young or old conventional mice was transferred to young germ-free (GF) mice. Four weeks after gut microbiota transfer immune cell populations in spleen, Peyer's patches, and mesenteric lymph nodes from conventionalized GF mice were analyzed by flow cytometry. In addition, whole-genome gene expression in the ileum was analyzed by microarray. Gut microbiota composition of donor and recipient mice was analyzed with 16S rDNA sequencing. Here, we show by transferring aged microbiota to young GF mice that certain bacterial species within the aged microbiota promote inflammaging. This effect was associated with lower levels of Akkermansia and higher levels of TM7 bacteria and Proteobacteria in the aged microbiota after transfer. The aged microbiota promoted inflammation in the small intestine in the GF mice and enhanced leakage of inflammatory bacterial components into the circulation was observed. Moreover, the aged microbiota promoted increased T cell activation in the systemic compartment. In conclusion, these data indicate that the gut microbiota from old mice contributes to inflammaging after transfer to young GF mice.

KW - Aging

KW - Germ-free mice

KW - Gut microbiome

KW - Immune system

KW - Inflammaging

U2 - 10.3389/fimmu.2017.01385

DO - 10.3389/fimmu.2017.01385

M3 - Article

VL - 8

JO - Frontiers in Immunology

JF - Frontiers in Immunology

SN - 1664-3224

M1 - 1385

ER -

Fransen F, van Beek AA, Borghuis T, El Aidy S, Hugenholtz F, van der Gaast - de Jongh C et al. Aged gut microbiota contributes to systemical inflammaging after transfer to germ-free mice. Frontiers in Immunology. 2017 Nov 2;8. 1385. https://doi.org/10.3389/fimmu.2017.01385