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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

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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 3

Colon RNAseq reveals a macrophage signature in the obese gut, with mitigation of these effects by oligofructose.

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Colon RNAseq reveals a macrophage signature in the obese gut, with mitig...
Transcriptome analysis of RNA extracted from colons of lean and obese mice with 4-weeks supplementation with cellulose (C) or oligofructose (OF). (A) The heatmap depicts clustering of 145 differentially expressed genes in obese compared with lean mice. Each column represents the expression profile of an individual mouse in each experimental group. (B) Cell type enrichment analysis was performed, depicting the most represented cell type signatures in the up- and downregulated gene sets. The percent of genes upregulated in obese colon associated with the intestinal, macrophage (MΦ), or other cell clusters is depicted in the inset pie chart. (C) The heatmap depicts clustering of 140 differentially expressed genes in obese-OF compared with obese-C. Each column represents the expression profile of an individual mouse in each experimental group. (D) Cell type enrichment analysis was performed, identifying the most represented cell type signatures in the up- and downregulated gene sets. The percent of genes upregulated in obese colon associated with the intestinal, MΦ, or other cell clusters is depicted in the inset pie chart. In B and D, the enrichment signature for intestinal cell types is denoted with green bars, macrophages with red bars, and stem cells with orange bars.

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