Microbiome linked to arthritis

​Arthritis has long been considered a problem of overuse - particularly in the obese. The idea is that heavy loading of the joints just wears them out. But a new study suggests that we may be blaming the wrong culprit, and that the bacteria in the gut may have more to do with arthritis than the fat that lies over it.

The first hint that this might be the case, according to Michael Zuscik, an arthritis researcher at the University of Rochester, was a paradox.

"We realized that even though we think of overloading of the joints in in the context of obesity as the problem that accelerates degeneration, some joints that don't actually carry any weight actually also degenerate"

This made Dr. Zuscik and his team wonder if the problem of osteoarthritis in the obese was inflammation, rather than overuse, and in particular if it was inflammation caused by a problem with gut bacteria. If this was the case, then it might be possible to stop obesity-related arthritis by manipulating the gut bacteria.

Feeding gut bacteria to fight inflammation

In experiments in obese mice, Zuscik and his group investigated a common gut bacterium that has been known to reduce inflammation called Bifidobacterium pseudolongum. This bacteria is thought to have various health-boosting benefits and is commonly added to probiotic yogurt.

Obesity is a known risk for arthritis, but new research suggests it's inflammation, rather that overloading of the joints, that does the damage.

Rather than add the bacteria to the diet of the mice directly, the team took a different approach. Bifidobacteria thrive on a fibre that is indigestible by mice and humans called oligofructose. By adding oligofructose to the diet of the experimental mice, they were able to boost the population of these beneficial bacteria.

The results were dramatic, says Zuscik. "Molecules that drive inflammatory effects were reduced," and the mice experienced "almost complete protection from the acceleration of arthritis that the high fat diet in obesity causes."

Zuscik suggests two possible mechanisms for how the bacteria might be reducing the inflammation and resulting arthritis. One is that it is out-competing a different bacteria in the gut that is causing the inflammation. The other is that Bifidobacteria produce waste products that act to damp inflammation. "Basically pseudolongum poop — those molecules may actually be very supportive of interesting biological effects in the human system."

The human body is more microbes than human. If we took all the bacteria off and out of a human body and put them in a bucket, they'd weigh three pounds - about as much as the human brain. (Alonnardi, cc-by-sa-3.0)

The next step in the work is to see if the Bifidobacteria produce the same inflammation-damping results in humans. Zuscik thinks this work could be completed quickly, since the bacteria are already available as a nutritional supplement, and work in humans would require no complicated drug approvals.

Research on the microbiome has exploded in recent years, and Zuscik thinks it clearly has enormous potential still.

"I think that we have to open our minds to the relationships that we have with the microbes that live with us and live in us. Two hundred and fifty thousand years of human evolution has set up a set of relationships that we don't fully understand and that may in fact be very important for supporting health, and in those relationships could be the next big therapeutic advances."

Figuring out how to turn gut bacteria into a solid team

One of the big challenges in understanding the microbiome is that it's so complex. Billions of bacteria representing thousands of species and strains all coexist in a complex ecosystem within us.

Increasingly we're understanding that many microbiome associated disorders are a result of this ecosystem going out of balance. This might be because certain species overgrow, or others don't grow enough. It's not always one good or bad actor, but the balance between many different actors.

Understanding the interactions between these different microbes is an enormous task, but a necessary one if we're to understand how to manipulate the bacteria in the interests of our health.

Ophelia Venturelli, a professor of of biochemistry at the University of Wisconsin-Madison and her colleagues have been trying to find ways to disentangle the complex relationships between bacteria by investigating how they interact.

By isolating different species and seeing how they relate to each other one-on-one, she's hoping to gradually build a bigger picture of how many species living together interact in the form of computational model, which so far, she's had moderate success.

Eventually, this should make it possible to predict how interventions, like antibiotics or probiotics, can correct problems with the microbiome that cause health disorders.