May 1, 2018

Dietary fiber protects obese mice from arthritis

At a Glance

  • A study in obese mice found that boosting the growth of certain gut bacteria with a fiber known as oligofructose reduced osteoarthritis.
  • The results suggest new approaches for treating osteoarthritis in people who are obese.

Being obese puts you at risk for many health problems, such as heart disease and diabetes. Having excess weight also increases the risk of osteoarthritis. Osteoarthritis is an inflammatory disease that involves the breakdown of cartilage, the tissue that covers the ends where two bones meet to form a joint. This allows the bones to rub together, causing pain and swelling. Other than replacing the joint, there’s no effective treatment for osteoarthritis.

Researchers have long thought that obese people were at risk of osteoarthritis because of the extra strain on their joints, such as the knees. Recent studies have found that the high-fat diets that obese people may consume can cause changes in gut microbe populations, allowing inflammation-promoting microbes to flourish. The immune cells and molecules involved in inflammation can spread from the gut to all tissues of the body through the bloodstream. That system-wide inflammation might contribute to osteoarthritis.

Changes in diet can enhance the growth of helpful microbes in your gut and crowd out inflammation-promoting microbes. Certain bacteria, such as some bifidobacteria, can reduce inflammation in the body through their byproducts. These microbes can ferment oligofructose, a type of dietary fiber found in bananas and other plants. In contrast, some other dietary fibers, such as cellulose, pass out of the body without being touched.

A team of scientists led by Drs. Michael J. Zuscik, Robert A. Mooney, and Steven R. Gill at the University of Rochester investigated whether promoting the growth of helpful microbes with oligofructose in obese mice would reduce knee osteoarthritis. The work was funded by NIH’s National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) and National Center for Advancing Translational Sciences (NCATS). Results were published online on April 19, 2018, in JCI Insight.

The researchers supplemented the diets of obese and lean mice with either oligofructose or cellulose as a control. Three months later, neither fiber had reduced obesity. However, for both obese and lean mice, the overall diversity of microbes in the gut shifted after receiving oligofructose. Notably, Bifidobacterium pseudolongum thrived with oligofructose while the proportion of inflammation-promoting microbes dropped.

The researchers analyzed the gut’s transcriptome—the complete set of active genes (expressed RNA). Obesity seemed to ramp up immune cell activity, suggesting an inflammatory effect in the gut. This effect was reduced in mice provided oligofructose. Blood tests also revealed a reduction in levels of immune system chemicals linked to obesity or inflammation in the mice treated with oligofructose. This suggests that oligofructose may reduce the widespread inflammation associated with obesity.

The team also looked for signs of inflammation and tissue degeneration in the knee joints of mice after surgical injury. Whereas the knees of obese mice had inflammation and osteoarthritis, the knees of oligofructose-treated obese mice did not and were similar to those of the lean mice. Taken together, these findings suggest that giving obese mice oligofructose can reduce inflammation and tissue degeneration at the knee joint.

“There are no treatments that can slow progression of osteoarthritis—and definitely nothing reverses it,” explains lead author Dr. Eric M. Schott. “But this study sets the stage to develop therapies that target the microbiome and actually treat the disease.”

—by Geri Piazza

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References: Targeting the gut microbiome to treat the osteoarthritis of obesity. Schott EM, Farnsworth CW, Grier A, Lillis JA, Soniwala S, Dadourian GH, Bell RD, Doolittle ML, Villani DA, Awad H, Ketz JP, Kamal F, Ackert-Bicknell C, Ashton JM, Gill SR, Mooney RA, Zuscik MJ. JCI Insight. 2018 Apr 19;3(8). pii: 95997. doi: 10.1172/jci.insight.95997. [Epub ahead of print]. PMID: 29669931.

Funding: NIH’s National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) and National Center for Advancing Translational Sciences (NCATS).