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 1

Oligofructose converts the obese gut microbiome to a lean diversity profile.

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Oligofructose converts the obese gut microbiome to a lean diversity prof...
(A) Nonmetric multidimensional scaling (NMDS) was applied to the pairwise distance matrix between representative microbial rDNA analyses of fecal samples from lean and obese mice supplemented with cellulose (C) or oligofructose (OF). NMDS 1 and 2 portray similar samples as closer together and dissimilar samples as farther apart. The x axis represents time starting immediately prior to initiation of supplements and progressing to termination of the experiment. (B) Principal coordinate analysis was performed on all samples from each experimental group, excluding the time point prior to initiation of treatment. Each symbol represents 1 sample, with the distance between samples in 3-dimensional space corresponding to the dissimilarity between them. For each of the 4 main phyla identified, biplot analysis was performed. Gray spheres were positioned based on the weighted average of the coordinates of the samples that contained that phylum and were sized based on the weighted average of the phylum’s relative abundance in each sample. (C) The average relative abundance of phyla within in each experimental group (n = 3 at each time point) is depicted in the bar chart. The ratio of the relative abundance of Bacteriodetes to Firmicutes for each group was calculated and averaged over all nonzero time points, as was the percent abundance of the 4 most prevalent phyla (D). Cladograms were constructed showing taxa that are significantly enriched in lean versus obese comparison (E), the lean-C versus lean-OF comparison (F), and the obese-C versus obese-OF comparison (G).