Could Bacterial Changes in the Blood Play a Role in Celiac Disease?

A recent research study from Massachusetts General Hospital points to an intriguing new way to look at celiac disease—by studying its connection to bacterial changes in the blood.

In a small proof-of-concept study, a team led by Gloria Serena, PhD, analyzed the blood and gut microbiomes of 10 adult patients with active celiac disease, 10 patients with celiac disease in remission (due to following a gluten-free diet) and 10 healthy controls.

The team found signature alterations in the blood microbiome of celiac patients when compared to healthy volunteers. Interestingly, most of these differences could be seen in both patients with an active form of the disease, and those with the disease in remission due to following a gluten-free diet.

The findings suggest that these alterations are not just a result of disease activity in the intestine, but they may be a common characteristic of all celiac patients. The differences could also contribute to the onset of symptoms in individuals who are genetically predisposed to celiac disease.  

“It is a preliminary study, but I think it has a lot of points that we can work on and are worth studying,” says Serena, a pediatric research fellow in the lab of Alessio Fasano, MD, at the hospital’s Mucosal Immunology and Biology Research Center.

The Blood Microbiome

If you haven’t heard much about the blood microbiome before, you’re not alone. It’s still a relatively new concept, Serena says. For many years, blood was believed to be sterile. It wasn’t until the 1970s that scientists found evidence of dormant (non-replicating) bacteria in the blood.

With the recent development of a technique for identifying bacterial DNA known as 16S sequencing, researchers have been able to show what the blood microbiome looks like in healthy individuals, as well as identify some disease-specific differences in individuals with liver cirrhosis, type 2 diabetes and some cardiac diseases.

“In celiac disease, we know that the alteration of the gut microbiome plays a major role in the progression of the disease, Serena says. “I thought, why not look at the blood microbiome, too? To my knowledge, no one had done that before.”

Next Steps and Long-Term Potential

Serena would like to confirm the findings by increasing the scope of the study to include hundreds of samples per group.

She’d also like to learn more about the role and function of celiac-related bacteria in the blood. While 16S sequencing can identify the presence of bacterial DNA, it doesn’t tell you if the bacteria are active or playing a role in the disease process, she explains.

“If we could find bacteria that are unique in the blood microbiome for celiac patients, this could be an additional biomarker that can be used when diagnosis through serology (blood tests) or endoscopy are not as clear.”

Further study could also provide insights into the role of the blood microbiome in other immune-related disorders (disorders in which the body’s immune cells start attacking healthy cells).

“Celiac disease is unique among the autoimmune disorders because it is the only one for which we know the genetic predisposition as well as the external trigger, which is gluten,” Serena explains. “Other diseases don’t have this luxury.”

While the possibilities are promising, Serena knows there is much work to be done in the lab before the findings can be translated to the clinic.

“Every kind of science we do here is with the final goal of helping the patient, and I am personally celiac, so I love to work on celiac disease,” she says. “It is very early, but if you wanted to dream, knowing a little more about the blood microbiome—how it works and how it functions in the context of celiac disease—could have so many possibilities.”


About the Mass General Research Institute
Massachusetts General Hospital is home to the largest hospital-based research program in the United States. Our researchers work side-by-side with physicians to develop innovative new ways to diagnose, treat and prevent disease.
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