Scientists have known for some time that microbiota likely drive the gut inflammation and clinical relapses in patients with inflammatory bowel disease (IBD). Drugs used to treat these conditions do not directly affect the microbiome.

A new study co-sponsored by Cincinnati Children’s and Connecticut Children’s Medical Center in Hartford is exploring the potential benefits of prebiotics in restoring a healthy microbiome in children with IBD. Specifically, the study is testing three different doses of the prebiotic 2’-fucosyllactose (2FL), an oligosaccharide that is present in breast milk. It is the first National Institutes of Health-sponsored, randomized controlled trial to study 2FL.

Synthetic 2FL is available in powdered form, and can be mixed into a beverage. Patients assigned to one of the 2FL groups continue to follow their established treatment plan, and take the supplement for one month (others take a placebo). “We will follow up with these patients three months after their last dose to see if their microbiome shows beneficial changes,” says Lee (Ted) Denson, MD, principal investigator of the 2FL study and director of the Schubert-Martin IBD Center at Cincinnati Children’s. “If the results are promising, we’ll design a new study to see whether 2FL helps keep patients with IBD in remission.”

Denson and his colleagues published two research studies in the last year that support the rationale for the 2FL study. The first, published in JCI Insight (Sept. 20, 2018), showed that intestinal microbiota may induce important epigenetic changes within a complex network of about 300 inflammatory genes. A trigger, such as stress or a viral infection, can cause these genes to be expressed at a high level, resulting in a flare of IBD symptoms. The network of genes affected by microbiota includes dual oxidase 2 (DUOX2), which previous research has identified as a key driver for inflammation. When mice in a previous study were given 2FL, one of the effects was a reduction in the expression of DUOX2.

The other study, published in The Lancet (Apr. 27, 2019), establishes a clinical model to help physicians predict which drug is likely to be most effective for individual patients, based on pretreatment clinical, genetic and microbial factors. Specific to the microbiome, the study showed that an antimicrobial peptide gene signature and an abundance of Ruminococcaceae, and Sutterella were independently associated with week 52 corticosteroid-free remission. These are the same bacteria being targeted in the 2FL study.

Denson says that the use of prebiotics would represent a fundamental shift in clinical practice toward personalized microbial therapeutic interventions.

“This 2FL study gets us a step closer to finding combinations of medication and nutritional supplements that will work better than medications alone—an approach that patients and families are certainly eager to try,” Denson explains.

Patient recruitment for the 2FL study begins in 2019, with an enrollment goal of 160 patients. The study is open to patients age 11 to 25 who are doing well on Remicade^® (infliximab) or Humira^® (adalimumab).

Download printable version