학술논문
Aging-Associated Augmentation of Gut Microbiome Virulence Capability Drives Sepsis Severity.
Document Type
Academic Journal
Author
Colbert JF; Department of Medicine, University of Colorado School of Medicine, Aurora, Colorado, USA.; Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, Colorado, USA.; Rocky Mountain Regional Veterans Affairs Medical Center, Aurora, Colorado, USA.; Kirsch JM; Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, Colorado, USA.; Erzen CL; Department of Medicine, University of Colorado School of Medicine, Aurora, Colorado, USA.; Langouët-Astrié CJ; Department of Medicine, University of Colorado School of Medicine, Aurora, Colorado, USA.; Thompson GE; University of Colorado, Boulder, Colorado, USA.; McMurtry SA; Department of Medicine, University of Colorado School of Medicine, Aurora, Colorado, USA.; Kofonow JM; Department of Medicine, University of Colorado School of Medicine, Aurora, Colorado, USA.; Robertson CE; Department of Medicine, University of Colorado School of Medicine, Aurora, Colorado, USA.; Kovacs EJ; Department of Surgery, University of Colorado School of Medicine, Aurora, Colorado, USA.; Sullivan RC; Department of Medicine, University of Colorado School of Medicine, Aurora, Colorado, USA.; Hippensteel JA; Department of Medicine, University of Colorado School of Medicine, Aurora, Colorado, USA.; Sawant NV; Department of Biological Sciences, University of Texas at Dallas, Richardson, Texas, USA.; De Nisco NJ; Department of Biological Sciences, University of Texas at Dallas, Richardson, Texas, USA.; Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.; McCollister BD; Department of Medicine, University of Colorado School of Medicine, Aurora, Colorado, USA.; Schwartz RS; Department of Medicine, University of Colorado School of Medicine, Aurora, Colorado, USA.; Rocky Mountain Regional Veterans Affairs Medical Center, Aurora, Colorado, USA.; Horswill AR; Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, Colorado, USA.; Rocky Mountain Regional Veterans Affairs Medical Center, Aurora, Colorado, USA.; Frank DN; Department of Medicine, University of Colorado School of Medicine, Aurora, Colorado, USA.; Duerkop BA; Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, Colorado, USA.; Schmidt EP; Department of Medicine, University of Colorado School of Medicine, Aurora, Colorado, USA.; Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.
Source
Publisher: American Society for Microbiology Country of Publication: United States NLM ID: 101519231 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2150-7511 (Electronic) NLM ISO Abbreviation: mBio Subsets: MEDLINE
Subject
Language
English
Abstract
Prior research has focused on host factors as mediators of exaggerated sepsis-associated morbidity and mortality in older adults. This focus on the host, however, has failed to identify therapies that improve sepsis outcomes in the elderly. We hypothesized that the increased susceptibility of the aging population to sepsis is not only a function of the host but also reflects longevity-associated changes in the virulence of gut pathobionts. We utilized two complementary models of gut microbiota-induced experimental sepsis to establish the aged gut microbiome as a key pathophysiologic driver of heightened disease severity. Further murine and human investigations into these polymicrobial bacterial communities demonstrated that age was associated with only subtle shifts in ecological composition but also an overabundance of genomic virulence factors that have functional consequence on host immune evasion. IMPORTANCE Older adults suffer more frequent and worse outcomes from sepsis, a critical illness secondary to infection. The reasons underlying this unique susceptibility are incompletely understood. Prior work in this area has focused on how the immune response changes with age. The current study, however, focuses instead on alterations in the community of bacteria that humans live with within their gut (i.e., the gut microbiome). The central concept of this paper is that the bacteria in our gut evolve along with the host and "age," making them more efficient at causing sepsis.
Competing Interests: The authors declare no conflict of interest.
Competing Interests: The authors declare no conflict of interest.