Meaningful Mouse Droppings

Taneja and her colleagues studied the fecal matter of 86 mice, including 41 with the 0401 allele and 45 with the 0402 allele, all given the same diet and kept in the same controlled environment. “Everything was the same except the genes they were carrying. We studied their stool samples and looked at what kind of immune response they had,” she says. What they confirmed was that the droppings of the mice with the 0401 gene were dominated by a number of Clostridium-like bacteria, especially allobaculum stercoricanis and parabacteroides distasonis. In contrast, the 0402-carrying mice were rich in two other types of bacteria, Porphyromonadaceae and Bifidobacteria.

“What we have shown is that there is an imbalance to begin with in mice with the gene,” Taneja says. These foreign organisms that we are all carrying around in our bodies may trigger the production of inflammatory cytokines, she notes. 

Altering that mix of bugs – possibly through dietary changes but more likely through targeted drug therapy someday – could help halt that RA-triggering process, she speculates. “We are trying to do something to rebalance what we already have in our guts. Scientists are realizing this more than ever before. We could treat arthritis by altering the bugs in the gut and making them in balance.”

Could dietary changes have a meaningful effect on gut bacteria? Another group of researchers at the University of Illinois’ department of animal sciences recently examined the intestinal flora in adult male humans who ate various types of dietary fiber. Twenty men were given three snack bars a day to eat in addition to their normal, controlled diets. One group of men were given bars with no dietary fiber, another group was given bars with polydextrose, and a third group was given bars with soluble corn fiber.

After examining the men’s fecal matter, the scientists found that the type of fiber the men ate had a strong effect on the levels of certain gut bacteria in their bodies. Eating more fiber significantly boosted the levels of different bacteria in the body, the researchers found. The men who ate soluble corn fiber had higher levels of Lactobacillus, a probiotic believed to be beneficial to digestive health. Both groups eating higher fiber had higher levels of Faecalibacterium prausnitzii, a bacteria believed to have anti-inflammatory properties also. Yet they also had higher levels of Clostridiaceae, the bacteria found in the guts of mice in Taneja’s study that might correlate to susceptibility to RA.

Gut bacteria’s possible connections to inflammation or the triggering of autoimmune disease is a “fascinating field of research,” says Dr. Scher. More research obviously is needed to determine how these findings may relate to the triggering of RA in humans, he says.

Guts and Gums

Dr. Scher and his colleagues examined the bacteria present in the inflamed gums of people with RA and concluded that there may be an increase in certain bugs in people with RA. Scher presented his findings at the 2011 Annual Meeting of the American College of Rheumatology in Chicago. His current research, funded by the National Institutes of Health, looks at microbiota, or bacteria living within various body cavities, and the development of diseases like RA.

“Gut bacteria have been associated to many autoimmune and rheumatic diseases. Intestinal microbiota are extremely helpful in providing humans with metabolic functions we do not have,” he says, functions like processing vitamins and complex sugars. These bugs also play a role in helping our immune systems mature. 

“Moreover, many mouse and rat models have proved that gut microbiota are sufficient to trigger joint disease,” Dr. Scher adds, including Whipple’s disease and reactive arthritis in humans. “Surveying the gut bacterial populations in different diseases such as RA is a first step into understanding whether they may act as triggering factors for joint disease.”

Despite the intriguing headlines, Dr. Scher says it is too early to firmly say whether certain gut bacteria predicts a risk for RA development in humans. “We are only looking at the tip of the iceberg,” he says. 

We don’t yet understand what processes those bacteria may kick into motion in a human body. “The association with bacteria will be by no means synonymous to causation. Understanding what are those bacteria doing, and how they differ in their metabolic and enzymatic functions will be needed,” he adds.