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

Publication date: 12 April 2017
Source:Cell Host & Microbe, Volume 21, Issue 4
Author(s): 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
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.

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Teaser

Systemic inflammation increases with age, but the underlying causes are debated. Using young and old germ-free and conventional mice, Thevaranjan et al. demonstrate that age-related microbiota changes drive intestinal permeability, age-associated inflammation, and decreased macrophage function. Reducing TNF levels rescues microbiota changes and protects old mice from intestinal permeability.


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