On a quest to improve treatments for inflammatory bowel disease

September 5, 2017, Gladstone Institutes

Scientist Shomyseh Sanjabi, PhD, joined the Gladstone Institutes seven years ago, and she brought with her a special type of mice that develop inflammatory bowel disease (IBD). Coincidentally, microbiome expert Katherine Pollard, PhD, was looking for a model to study the disease. Particularly because she is an IBD patient herself.

That's how an unlikely collaboration started between an immunology researcher, Sanjabi, and a biostatistician, Pollard. They set out to uncover the role played by bacteria in the gut in IBD.

Your gut contains trillions of bacteria and tiny microbes—collectively called the microbiome—that mainly help with digestion and other bodily functions. But these bacteria have also been linked to IBD. Studies have shown that the microbiome is very different in sick and healthy individuals.

However, scientists don't know if bacteria are responsible for causing IBD, or if IBD causes bacteria in the gut to change. Equipped with Sanjabi's mouse model, she and Pollard realized they now had the tools to answer this "chicken or the egg" question.

Ulcerative colitis and Crohn's disease are the two most common forms of IBD, which is an increasingly prevalent disease in which the immune system attacks tissues in the intestine. Symptoms vary between Improvpatients and can include severe diarrhea, abdominal pain, fatigue, and unintended weight loss.

Pollard has been living with IBD for the past decade.

"Like most patients, I didn't know I had a chronic disease for many years," says Pollard, director of the Convergence Zone at Gladstone. "At first, many people think they may be lactose intolerant or have an allergy to gluten. Then, when the symptoms are serious, they realize they have IBD."

The exact cause of IBD remains unknown. Because is hard to predict who will develop the disease, human studies typically occur after patients are quite sick. At that point, it is hard to determine if gut bacteria triggered IBD.

"These studies are valuable, but they don't reveal much about what causes the disease or how it evolves," explains Gladstone Assistant Investigator Sanjabi. "The gave us an opportunity to overcome the challenges of a human study and finally conduct a longitudinal study on IBD. We gathered data from birth to adulthood, so we could see the onset and progression of the disease."

The scientists got to work. They monitored the mice's immune system and collected on a weekly basis. The study's first authors, Thomas Sharpton and Svetlana Lyalina, then analyzed the full DNA sequence of these bacteria.

"We detected changes in the genes of the gut bacteria before any symptom of IBD appeared," says Sanjabi, who is also an assistant professor at the University of California, San Francisco (UCSF). "Most of the changes in bacteria happened at the same time as the immune system started showing signs of an autoimmune disease. This model can help us identify exactly when the disease starts."

The scientists' findings, published today in the open-access journal mSystems, associate the progression of IBD with parallel changes in what gut bacteria are doing over time. They found that these changes in the microbiome may represent an early indicator of the disease.

Current therapies for IBD are like Band-Aids. They treat the symptoms, but not the root of the problem. If the researchers can pinpoint early signs of IBD and predict who might get sick, they could help develop diagnostic tools and find treatments to address the cause of disease.

"IBD drugs also increase risk for serious infections," says Pollard, also a UCSF professor. "Whenever I travel or visit a hospital, I need to stop my treatment, because it weakens my immune system. We need to discover what contributes to the development and severity of the disease to ensure accurate and effective health care."

Now, Sanjabi and Pollard know more than when they started. But they also have more questions than when they began.

They suspect that IBD is caused by the dynamic interaction between an abnormal immune response and opportunistic bacteria. Their next step will be to test whether they can trigger IBD by manipulating specific .

"This project was so personal because of Katie's own struggles with IBD," says Sanjabi. "She, and so many other patients, deserve better options. My hope is to, one day, develop targeted antibiotic treatments that could get rid of specific in the gut causing the disease."

Pollard's hope is the same.

"I'm encouraged by our promising results," says Pollard. "We could potentially analyze the microbiome of patient stool to classify and even predict . That would be an enormous step in the right direction."

Explore further: Mapping the gut microbiome to better understand its role in obesity

More information: Development of Inflammatory Bowel Disease Is Linked to a Longitudinal Restructuring of the Gut Metagenome in Mice, DOI: 10.1128/mSystems.00036-17 , http://msystems.asm.org/content/2/5/e00036-17

Related Stories

Mapping the gut microbiome to better understand its role in obesity

February 14, 2015
Several recent science studies have claimed that the gut microbiome—the diverse array of bacteria that live in the stomach and intestines—may be to blame for obesity. But Katherine Pollard, PhD, a senior investigator ...

How the microbiome could tackle antibiotic resistant infections in the lungs

August 10, 2017
Understanding how microbes contribute to respiratory health and immunity could help tackle drug resistant infections in the lungs, say scientists.

New research suggests more sensitive approaches to detect and monitor inflammatory bowel disease

May 15, 2017
A University of Manchester test on the mucus lining of the intestine, performed in mice, has found changes in bacteria that could lead to inflammatory bowel disease 12 weeks earlier than previously possible through looking ...

Microbiomes more in flux in patients with inflammatory bowel disease

February 13, 2017
Patients with inflammatory bowel disease are more likely to see dramatic shifts in the make-up of the community of microbes in their gut than healthy people, according to the results of a study published online Feb. 13 in ...

Single fungus amplifies Crohn's disease symptoms

June 21, 2017
A microscopic fungus called Candida tropicalis triggered gut inflammation and exacerbated symptoms of Crohn's disease, in a recent study conducted at Case Western Reserve University School of Medicine.

Recommended for you

Scientists emulate the human blood-retinal barrier on a microfluidic chip

January 24, 2018
For some years, scientists have been seeking ways to reduce animal testing and accelerate clinical trials. In vitro assays with living cells are an alternative, but have limitations, as the interconnection and interaction ...

Forces from fluid in the developing lung play an essential role in organ development

January 23, 2018
It is a marvel of nature: during gestation, multiple tissue types cooperate in building the elegantly functional structures of organs, from the brain's folds to the heart's multiple chambers. A recent study by Princeton researchers ...

Anemia discovery offers new targets to treat fatigue in millions

January 22, 2018
A new discovery from the University of Virginia School of Medicine has revealed an unknown clockwork mechanism within the body that controls the creation of oxygen-carrying red blood cells. The finding sheds light on iron-restricted ...

More surprises about blood development—and a possible lead for making lymphocytes

January 22, 2018
Hematopoietic stem cells (HSCs) have long been regarded as the granddaddy of all blood cells. After we are born, these multipotent cells give rise to all our cell lineages: lymphoid, myeloid and erythroid cells. Hematologists ...

How metal scaffolds enhance the bone healing process

January 22, 2018
A new study shows how mechanically optimized constructs known as titanium-mesh scaffolds can optimize bone regeneration. The induction of bone regeneration is of importance when treating large bone defects. As demonstrated ...

Researchers illustrate how muscle growth inhibitor is activated, could aid in treating ALS

January 19, 2018
Researchers at the University of Cincinnati (UC) College of Medicine are part of an international team that has identified how the inactive or latent form of GDF8, a signaling protein also known as myostatin responsible for ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.