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

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

来源：Cell Host & Microbe, 2017, 21(4): 455-+.

DOI：10.1016/j.chom.2017.03.002

• UPPER RESPIRATORY-TRACT
• NECROSIS-FACTOR-ALPHA
• BACTERIAL COMMUNITIES
• ELDERLY POPULATION
• IMMUNE ACTIVATION
• CROHNS-DISEASE
• GUT MICROBIOTA
• HIV-INFECTION
• TNF-ALPHA
• PNEUMONIA

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 germfree 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.

• 出版日期2017-4-12