Abstract
AbstractCartilage microbial DNA patterns have been recently characterized in osteoarthritis (OA). The objectives of this study were to evaluate the gut origins of cartilage microbial DNA, to characterize cartilage microbial changes with age, obesity, and OA in mice, and correlate these to gut microbiome changes. We used 16S rRNA sequencing performed longitudinally on articular knee cartilage from germ-free (GF) mice following oral microbiome inoculation and cartilage and cecal samples from young and old wild-type mice with/without high-fat diet-induced obesity (HFD) and with/without OA induced by destabilization of the medial meniscus (DMM) to evaluate gut and cartilage microbiota. Microbial diversity was assessed, groups compared, and functional metagenomic profiles reconstructed. Findings were confirmed in an independent cohort by clade-specific qPCR. We found that cartilage microbial patterns developed at 48 h and later timepoints following oral microbiome inoculation of GF mice. Alpha diversity was increased in SPF mouse cartilage samples with age (P = 0.013), HFD (P = 5.6E-4), and OA (P = 0.029) but decreased in cecal samples with age (P = 0.014) and HFD (P = 1.5E-9). Numerous clades were altered with aging, HFD, and OA, including increases in Verrucomicrobia in both cartilage and cecal samples. Functional analysis suggested changes in dihydroorotase, glutamate-5-semialdehyde dehydrogenase, glutamate-5-kinase, and phosphoribosylamine-glycine ligase, in both cecum and cartilage, with aging, HFD, and OA. In conclusion, cartilage microbial DNA patterns develop rapidly after the introduction of a gut microbiome and change in concert with the gut microbiome during aging, HFD, and OA in mice. DMM-induced OA causes shifts in both cartilage and cecal microbiome patterns independent of other factors.
Funder
National Institute of Arthritis and Musculoskeletal and Skin Diseases
National Institute of General Medical Sciences
Congressionally Directed Medical Research Programs
Publisher
Springer Science and Business Media LLC
Subject
Geriatrics and Gerontology,Aging
Reference57 articles.
1. Centers for Disease Control and Prevention (CDC). Prevalence of doctor-diagnosed arthritis and arthritis-attributable activity limitation--United States, 2010-2012. MMWR Morb Mortal Wkly Rep. 2013;62:869–73.
2. O’Toole PW, Jeffery IB. Gut microbiota and aging. Science. 2015;350:1214–5.
3. John GK, Mullin GE. The gut microbiome and obesity. Curr Oncol Rep. 2016;18:45.
4. Boer CG, Radjabzadeh D, Uitterlinden AG, Kraaij R, van Meurs JB. The role of the gut microbiome in osteoarthritis and joint pain. Osteoarthritis Cartilage. 2017;25:S10.
5. Clarke SF, Murphy EF, O’Sullivan O, Ross RP, O’Toole PW, Shanahan F, et al. Targeting the microbiota to address diet-induced obesity: a time dependent challenge. PLoS One. 2013;8:e65790.