Microbiome: How your bacteria affects psoriatic disease

| Melissa Leavitt

When Sylvia was 14, she ran for student council. The campaign brought on a lot of stress. It also brought on her first bout with psoriasis.

"I went to the doctor and they gave me some awful, milky white thing to try," said Sylvia, who asked that her last name not be used.

The topical medication didn't really work, she said, but eventually her plaques went away. Then, last August, more than 40 years later, they resurfaced on her scalp. On a friend's recommendation, she decided to try probiotics.

Within a day, she said, "my head stopped tingling." A few days later, her psoriasis disappeared, even a persistent patch in her eyebrow. She credits probiotics. "I am blown away," she said. "I'm not giving up on this."

Sylvia's not alone in her enthusiasm. Researchers are investigating how the microbes living on and in our bodies — known as our microbiome — could play a role in inflammatory diseases. Their interest is prompting many people with psoriasis and psoriatic arthritis to think about their own microbiome. Some take probiotics, which introduce new bacteria into the gut. Others eat certain foods to modify their microbiome.

On any given day, you can find thousands of posts about bacteria, probiotics and the microbiome on message boards such as NPF's online community, TalkPsoriasis.org. Patients share research and trade stories, trying to understand how it all relates to psoriatic disease.

Scientists are wondering the same thing, navigating the field with new discoveries.

"The microbiome in psoriasis is a new frontier," said Dr. Martin Blaser, the director of the Human Microbiome Program at New York University and author of "Missing Microbes: How the Overuse of Antibiotics Is Fueling Our Modern Plagues." He hopes that microbiome research will lead to better ways of diagnosing, treating and even preventing psoriasis.

"The outlook is promising," he said.

Microbes: Vital to our immune system

Microbes outnumber us. Our bodies have about 10 trillion cells each, but we host approximately 100 trillion microbial cells. The gut alone, which includes our stomach and intestines, is home to about three pounds of bacteria. Microbes also are, in some ways, smarter than us. They're not just taking up space; many actually tell parts of our immune system what to do.

We already know that our immune system targets microbes — that's how it defends us from harmful pathogens. Researchers now realize that some microbes are actually an important part of our immune defenses, controlling the development of key components of our immune system.

"Microbes have figured out our immune system in ways that we, as scientists, still don't fully understand," said Dr. Sarkis Mazmanian, a microbiologist at the California Institute of Technology.

We rely on our immune system to distinguish between microbial invaders that might make us sick and the harmless bacteria that are always inside us, said Mazmanian. Based on this distinction, the immune system decides when and when not to attack. But the immune system doesn't make this decision by itself.

"Part of the decision-making process is actually controlled by specific gut microbes," said Mazmanian.

In other words, the bugs are pulling the strings.

"Microbes have learned to flip certain switches in our bodies," Mazmanian said, explaining that some microbes induce immune cells called T-cells to promote inflammatory responses, and others induce T-cells to suppress inflammatory responses.

That means that microbes contribute to our body's decision on whether to launch an immune attack.

Dr. Yasmine Belkaid, an immunologist at the National Institutes of Health, described it as an educational process.

"A lot of what the microbes are doing is preparing the cells for subsequent encounters with pathogens," Belkaid said. "You constantly need these microbes to educate, to stimulate and to control the form of immunity that we're going to develop."

The immune system connection

If you don't get a good education, it's tough to do your job. That's why scientists are asking whether immune-mediated disorders such as psoriasis and psoriatic arthritis — when the body misfires and launches an inflammatory response against itself — could be caused by a disturbance in the microbiome.

To understand why the immune system needs microbes, you have to understand what happens to an immune system without any microbes. So scientists remove microbes from mice by raising them in germ-free conditions.

Then they watch what happens when these mice encounter certain germs. Several pivotal studies have found that the immune systems of these germ-free mice don't work very well.

An experiment involving germ-free mice engineered to have arthritis showed that, if they stayed in germ-free conditions, they only developed mild arthritis. However, when they ingested a certain kind of bacterium, they quickly developed a more severe form of the disease.

From this study, published in the June 2010 issue of the journal Immunity, scientists learned two important things: that throwing our bacteria off-balance can lead to inflammatory disease, and that this disease doesn't necessarily have to occur where the bacteria are located. That is, bacteria in the gut can trigger inflammation outside the gut.

Scientists can't create bug-free people to see if they develop immune system disorders. But they can look at the bugs that people with immune system disorders have to see whether any particular microbes might correlate to disease development.

Focus on psoriatic arthritis

Dr. Jose Scher, a rheumatologist at New York University, is exploring whether the gut microbiome of people with psoriatic arthritis differs from that of healthy people. His preliminary findings suggest that people with psoriatic arthritis may have less bacterial diversity, which means they have depleted supplies of some kinds of bacteria.

Blaser's taken a similar approach to the skin microbiome, analyzing whether people with psoriasis have certain microbes on their skin that might play a role in triggering the disease. His team has identified certain bacterial patterns that seem to be associated with psoriasis.

These patterns signal an imbalance in patients' microbial communities — what scientists call dysbiosis. The next step is determining whether dysbiosis can actually disrupt our immune systems so much that it causes immune system disorders. To get to the bottom of this, researchers need to track who develops psoriasis and psoriatic arthritis — and which microbes they're carrying around.

"The best studies, which are the most difficult to do, are studies of people who don't have psoriasis yet but will develop it," Blaser said.

These studies, called longitudinal studies, will tell researchers how the people who develop psoriasis are different from the people who don't, he said.

Scher thinks that longitudinal studies could be particularly useful for psoriatic arthritis.

"This is one disease where the risk factors are pretty well-known," he said. "If someone has psoriasis, there is a 20 to 30 percent chance that they will develop psoriatic arthritis."

Treat the bugs, treat the disease

Once scientists identify and understand the roles of the microbes found in people who develop psoriasis or psoriatic arthritis, they could use this knowledge to treat the root cause of the disease.

Therapies that target microbes would offer an alternative to drugs that suppress the immune system. Many medications treat psoriatic disease by disrupting the process that causes inflammation. But, Mazmanian said, some of these medications impair the body's ability to fight infectious viruses or bacteria.

Instead of completely shutting off inflammation, microbial therapies may be able to balance the pro-inflammatory and anti-inflammatory functions of our immune systems by restoring bacterial balance, Mazmanian said.

Therapies that balance an individual's microbiome — by eradicating some microbes or promoting others — may sound a lot like the antibiotics and probiotics we already have. But researchers emphasize that new treatments may be very different.

Take antibiotics, for instance. According to Blaser, patients might one day take antibiotics to treat the specific microbes involved in psoriasis.

"If we found that there are certain organisms that are particularly bad, we could develop new antibiotics to suppress or kill them," he said. "Not the antibiotics that are on the shelf today, but antibiotics that just target the bacteria we're interested in."

How probiotics would work

Probiotic treatments would be designed to have the opposite effect — instead of killing the bad bugs, they would promote the good ones, the ones that reduce inflammation involved in psoriatic disease. But these, too, would be different from what's on the market now.

Scientists may eventually develop an entirely new class of probiotics, Blaser said, that would be highly targeted to address psoriasis.

Some researchers are already investigating probiotic treatments. A 2013 study published in the journal Gut Microbes found that taking a certain microbe could reduce patients' levels of inflammatory proteins, or cytokines. However, the study didn't test enough patients to determine whether it would be an effective therapy.

Blaser cautioned that the probiotics available today in health food stores and pharmacies are largely unregulated and have not been tested for efficacy. Scher, too, warned that while probiotics could one day potentially be an effective treatment, "the emphasis is on the potential." But he recognized that patients are looking for new options.

A case for patient-researcher partnerships

Sylvia isn't the only patient who's happy with probiotics.

Ken Lassesen was diagnosed with psoriasis on his heels about 10 years ago. He tried a topical treatment, but the psoriasis kept coming back. A couple of years ago, he started taking probiotics for a different condition. His heels cleared up — and stayed clear, he said. He credits the improvement to probiotics.

For Tom Agoston, probiotics were more appealing than systemic or biologic drugs.

He's dealt with psoriasis on and off for years, and when it worsened about five years ago, he explored alternative treatments.

"I began to look at what else I could do besides taking a medication that would suppress part of my immune system," he said.

Like Lassesen, he started taking probiotics for a different condition but wondered if it would help his psoriasis. Even after a few months, he hasn't noticed much of a change. But he stays open-minded: "When it comes to a low-risk, sensible alternative approach, my philosophy is, why not try it?"

If patients do take probiotics, they should work closely with their doctor, said Dr. Veena Taneja, an immunologist at the Mayo Clinic.

Lassesen offered the same advice. He and his doctor are partners, he said, debating the pros and cons of different treatments.

"Her role is to flag problems, and my role is to be proactive," he said. "I do the research and bring her new ideas, and she tries to identify the risks in what I find."

Close partnerships between patients and doctors will become even more important as research progresses.

"You can see people who are not scientists being completely excited by this topic," Belkaid said. "The public can really become partners with scientists."

In fact, it was a patient who inspired Blaser to research the microbiome's relationship to psoriasis. That patient was his father, who has psoriasis. When his father took a medication for his gout, Blaser said, his psoriasis also cleared up.

After doing some research, Blaser learned that the medication had antimicrobial properties, so he began working to understand how targeting microbes could heal psoriasis.

Today, Blaser is both a patient and a researcher. He's developed psoriasis on his fingers and legs, he said.

"So I am very eager to improve therapy," he said.

Editor's note: Wondering if you are showing signs of psoriatic arthritis? Take a quiz and learn more about PsA.

 

 

 

 


Driving Discovery, Creating Community

This year, we’re celebrating 50 years of driving efforts to cure psoriatic disease and improve the lives of those affected. See how far we’ve come with this timeline of NPF’s history. But there’s still plenty to do, and we can’t do it without you! Learn how you can help our advocacy team shape the laws and policies that affect people with psoriasis and psoriatic arthritis – in your state and across the country. Help us raise funding to promote research into better treatments and a cure by joining Team NPF, where you can walk, run, cycle, play bingo or even create your own DIY event. Contact our Patient Navigation Center for free, personalized support for living a healthier life with psoriatic disease. And keep the National Psoriasis Foundation going strong by making a donation today! Together, we will find a cure.

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