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Age-associated microbial dysbiosis promotes intestinal permeability, systemic inflammation and macrophage dysfunction

Research output: Contribution to journalArticlepeer-review

  • Netusha Thevaranjan
  • Alicja Puchta
  • Christian Schulz
  • Avee Naidoo
  • J C Szamosi
  • Chris P. Verschoor
  • Dessi Loukov
  • Louis P Schenck
  • Jennifer Jury
  • Kevin P Foley
  • Jonathan D Schertzer
  • Maggie J Larche
  • Donald J Davidson
  • Elena F Verdu
  • Michael G Surette
  • Dawn M E Bowdish

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Original languageEnglish
Pages (from-to)455-466.E4
Number of pages16
JournalCell Host & Microbe
Volume21
Issue number4
Early online date12 Apr 2017
DOIs
Publication statusPublished - 12 Apr 2017

Abstract

Levels of inflammatory mediators in circulation are known to increase with age, but the underlying cause of this age-associated inflammation is debated. We find that, when maintained under germ-free conditions, mice do not display an age-related increase in circulating pro-inflammatory cytokine levels. A higher proportion of germ-free mice live to 600 days than their conventional counterparts, and macrophages derived from aged germ-free mice maintain anti-microbial activity. Co-housing germ-free mice with old, but not young, conventionally raised mice increases pro-inflammatory cytokines in the blood. In tumor necrosis factor (TNF)-deficient mice, which are protected from age-associated inflammation, age-related microbiota changes are not observed. Furthermore, age-associated microbiota changes can be reversed by reducing TNF using anti-TNF therapy. These data suggest that aging-associated microbiota promote inflammation and that reversing these age-related microbiota changes represents a potential strategy for reducing age-associated inflammation and the accompanying morbidity.

    Research areas

  • macrophage, immunoscience, microbiota, microbiome, inflammation, inflamm-aging, Streptococcus pneumoniae, host defense, elderly

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