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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 2

B.pseudolongum is a key microbe lost in obesity and restored following OF supplementation.

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B.pseudolongum is a key microbe lost in obesity and restored following ...
(A) Average species abundance was determined in fecal samples collected across the various time points (n = 3/time point), with relative average abundance for detected species depicted in the bar chart. (B) A heatmap was constructed comparing abundance of species that were either decreased in obesity and significantly restored following oligofructose supplementation (top segment) or increased in obesity and significantly suppressed following oligofructose supplementation (bottom segment). Species highlighted in green or red in A and B are presented quantitatively, with summary statistics calculated for Bifidobacterium pseudolongum (C), an uncharacterized species in the genus Bifidobacterium (D), an unidentifiable species in the family Peptococcaceae (E), and an unidentifiable species in the family Peptostreptococcaceae (F). Since microbial diversity did not significantly change temporally after initiation of prebiotic supplementation (Figure 1A), abundance data for all time points from 14 days and after were averaged for each experimental group for each of these 4 species in order to perform statistical analysis. Significant differences between groups were identified via 2-way ANOVA with a Tukey multiple comparison post-test (P values for the obesity effect are reported; **P < 0.01, ****P < 0.0001).

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