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

By Netusha Thevaranjan, Alicja Puchta, Christian Schulz, Avee Naidoo, J. Szamosi, C. Verschoor, Dessi Loukov, L. P. Schenck, J. Jury, K. Foley and 6 more. Cell Host and Microbe, 2017

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Summary 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.

Subfields: Biological Psychiatry, Molecular Biology, Physiology

View Paper: https://www.semanticscholar.org/paper/db1685efdfc5254c79c71d5fd8adbc1df38a0275

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Citations in the corpus

The Continuum of Aging and Age-Related Diseases: Common Mechanisms but Different Rates (2018, background): “On the other hand, GM dysbiosis has been associated with several diseases suggesting that alteration of its composition may be involved in disease-related mechanisms (268).”
Age and Age-Related Diseases: Role of Inflammation Triggers and Cytokines (2018, background): “Aging leads to changes in intestinal permeability in gut bacterial milieu (362), and the increased circulatory bacterial DNA observed associated with atherosclerosis support further investigation of the microbiome as a contributory factor to age-related inflammation and atherosclerosis.”
The gut microbiome: Relationships with disease and opportunities for therapy (2018, background): “A direct link between age-related gut microbiota changes and age-associated systemic inflammation has been established in a recent study, in which cohousing germ-free (GF) mice with old, but not young, microbiome-replete mice increased intestinal permeability and age-related inflammation (Thevaranja”
Inflammation and aging: signaling pathways and intervention therapies (2023, result): “Interestingly, two previous studies have indicated that changes in the relative abundance of gut microbiota are more likely to be influenced by inflammation rather than age, with TNF playing a significant role.(185,186) This suggests that the changes in gut microbiota are more closely related with i”