Abstract
Advanced age has been associated with alterations to the microbiome within the intestinal tract as well as intestinal permeability (i.e., “leaky gut”). Prior studies suggest that intestinal permeability may contribute to increases in systemic inflammation—an aging hallmark—possibly via microorganisms entering the circulation. Yet, no studies exist describing the state of the circulating microbiome among older persons. To compare microbiota profiles in serum between healthy young (20–35 years, n = 24) and older adults (60–75 years, n = 24) as well as associations between differential microbial populations and prominent indices of age-related inflammation. Unweighted Unifrac analysis, a measure of β-diversity, revealed that microbial communities clustered differently between young and older adults. Several measures of α-diversity, including chao1 (p = 0.001), observed species (p = 0.001), and phylogenetic diversity (p = 0.002) differed between young and older adults. After correction for false discovery rate (FDR), age groups differed (all p values ≤ 0.016) in the relative abundance of the phyla Bacteroidetes, SR1, Spirochaetes, Bacteria_Other, TM7, and Tenericutes. Significant positive correlations (p values ≤ 0.017 after FDR correction) were observed between IGF1 and Bacteroidetes (ρ = 0.380), Spirochaetes (ρ = 0.528), SR1 (ρ = 0.410), and TM7 (ρ = 0.399). Significant inverse correlations were observed for IL6 with Bacteroidetes (ρ = − 0.398) and TM7 (ρ = − 0.423), as well as for TNFα with Bacteroidetes (ρ = − 0.344). Similar findings were observed at the class taxon. These data are the first to demonstrate that the richness and composition of the serum microbiome differ between young and older adults and that these factors are linked to indices of age-related inflammation.
Highlights
Chronic low-grade inflammation is one of the most consistent biologic features of advanced age, evidenced by over 10,000 publications in this area (Buford 2017)
Aging is associated with several relevant changes to overall gut health including increases in intestinal permeability (Man et al 2015; Nicoletti 2015) as well as changes to the stability of the gut microbiome (Biagi et al 2010; Jeffery et al 2016)—the aggregate genetic material of microorganisms residing within the intestinal tract which contribute to regulating host health (Human Microbiome Project Consortium 2012)
We aimed to identify specific microbial DNA abundances significantly associated with circulating concentrations of interleukin 6 (IL6) and TNFα as well as insulin-like growth factor 1 (IGF1)—a hormone known to be intricately related to inflammatory cytokine production (Maggio et al 2013; Rajpathak et al 2008) and recently reported to be stimulated by microbiota (Yan et al 2016)
Summary
Chronic low-grade inflammation is one of the most consistent biologic features of advanced age, evidenced by over 10,000 publications in this area (Buford 2017). Aging is associated with several relevant changes to overall gut health including increases in intestinal permeability (Man et al 2015; Nicoletti 2015) as well as changes to the stability of the gut microbiome (Biagi et al 2010; Jeffery et al 2016)—the aggregate genetic material of microorganisms residing within the intestinal tract which contribute to regulating host health (Human Microbiome Project Consortium 2012) These changes are relevant in the present context as recent evidence indicates that changes in microbial composition and density can alter immunity and inflammation distal to the intestine (Belkaid and Naik 2013). The mechanisms through which gut dysbiosis could contribute to chronic, low-grade inflammation were unclear
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