Age-Associated Microbial Dysbiosis Promotes Intestinal Permeability, Systemic Inflammation, and Macrophage Dysfunction

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. Larché, Donald J. Davidson, Elena F. Verdú, Michael G. Surette, Dawn M.E. Bowdish

Research output: Contribution to journalArticlepeer-review

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.
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

Keywords

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

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