Targeting the gut microbiome to treat the osteoarthritis of obesity
Eric M. Schott, … , Robert A. Mooney, Michael J. Zuscik
Eric M. Schott, … , Robert A. Mooney, Michael J. Zuscik
Published April 19, 2018
Citation Information: JCI Insight. 2018;3(8):e95997. https://doi.org/10.1172/jci.insight.95997.
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Research Article Inflammation Microbiology

Targeting the gut microbiome to treat the osteoarthritis of obesity

Abstract

Obesity is a risk factor for osteoarthritis (OA), the greatest cause of disability in the US. The impact of obesity on OA is driven by systemic inflammation, and increased systemic inflammation is now understood to be caused by gut microbiome dysbiosis. Oligofructose, a nondigestible prebiotic fiber, can restore a lean gut microbial community profile in the context of obesity, suggesting a potentially novel approach to treat the OA of obesity. Here, we report that — compared with the lean murine gut — obesity is associated with loss of beneficial Bifidobacteria, while key proinflammatory species gain in abundance. A downstream systemic inflammatory signature culminates with macrophage migration to the synovium and accelerated knee OA. Oligofructose supplementation restores the lean gut microbiome in obese mice, in part, by supporting key commensal microflora, particularly Bifidobacterium pseudolongum. This is associated with reduced inflammation in the colon, circulation, and knee and protection from OA. This observation of a gut microbiome–OA connection sets the stage for discovery of potentially new OA therapeutics involving strategic manipulation of specific microbial species inhabiting the intestinal space.

Authors

Eric M. Schott, Christopher W. Farnsworth, Alex Grier, Jacquelyn A. Lillis, Sarah Soniwala, Gregory H. Dadourian, Richard D. Bell, Madison L. Doolittle, David A. Villani, Hani Awad, John P. Ketz, Fadia Kamal, Cheryl Ackert-Bicknell, John M. Ashton, Steven R. Gill, Robert A. Mooney, Michael J. Zuscik

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Figure 5

Oligofructose protects against accelerated posttraumatic osteoarthritis (PTOA) in obesity.

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Oligofructose protects against accelerated posttraumatic osteoarthritis ...
Two weeks after lean and obese mice were initiated on cellulose or oligofructose, sham or DMM surgery was performed and knee joints were collected 12 weeks later. Representative Safranin O/Fast Green stained sections in lean (A) and obese (B) mice are presented, with black dotted boxes denoting areas that are shown at higher magnification to the immediate right (scale bars: 100 μm) and yellow dotted lines demarcating the tide marks. Sections like those shown in A and B were used to perform histomorphometry on femur (C–F) and tibia (G–J) articular cartilage, as well as OARSI scoring (K). Black dotted lines in the bar graphs depict the value for the respective Sham-lean-cellulose negative control, bars represent the group mean (± SEM), and individual symbols depict the average of measurements made in 3 histologic levels from 6–8 individual joints. Significant differences between groups in C–K were identified via 2-way ANOVA with a Tukey multiple comparison post-test (P values for the obesity effect are reported when significance was achieved; *P < 0.05, **P < 0.01). Similar histology and histomorphometry performed in Sham-operated joints is presented in Supplemental Figure 4.