Newest Research out of the Celiac Center

Dr. Therrien performing an assay
Dr. Therrien performing an assay in the Celiac Center laboratory
GI fellows and researchers at BIDMC recently presented their work at the 18th- annual International Celiac Disease Symposium in Paris. Read summaries of their work below.
Use of Enteric-Release Budesonide in Non-Responsive Celiac Disease
Presenting author: Amelie Therrien, MD

Budesonide is a steroid that has a direct effect on the gut. While it has been previously shown to be effective to induce remission in adults with refractory celiac disease (RCD), it may also be used for non-responsive celiac disease (NRCD). Non-responsive celiac disease is defined as the persistence of signs or symptoms of celiac disease despite adhering to a gluten-free diet for at least 12 months. In this work, in collaboration with the Center for Celiac Research and Treatment, Massachusetts General Hospital, we reported that 50 patients received this steroid for debilitating symptoms attributed to NRCD (suspicion of RCD). Symptoms improved in 60% of them; 50% of those with mucosal damage in the small intestine also showed healing; however, the rate at which symptoms recurred after discontinuing the medication was high (70% of the responders). Most of the people with no response to budesonide were eventually given a diagnosis of irritable bowel syndrome in addition to their celiac disease. In conclusion, although it shows promising results, more studies and guidance are needed to integrate budesonide in the management of NRCD.  

Use of Cladribine for Ulcerative Jejunitis: A Single-Center Experience in North America
Presenting author: Amelie Therrien, MD

Ulcerative jejunitis is a rare complication of celiac disease (less than 0.5% of the celiac disease population). It presents with ulcers in the small intestines that may bleed, perforate (make a hole or tear) or obstruct. Various treatments may be tried, including surgery, steroids, and immunosuppressants. We recently used cladribine in three patients with ulcerative jejunitis that did not improve with budesonide. Cladribine is a mild chemotherapy that is given intravenously (through the veins) every day for five days. One patient was free of disease for 22 months after the treatment; another one has been free of the disease for 14 months. Although initial clinical improvement was seen in the study, one patient relapsed nine months after therapy and is now pursuing another treatment. In conclusion, cladribine may be a good option in patients with ulcerative jejunitis that do not respond to budesonide.

Efficacy of Pancreatic Enzyme Supplementation for Symptom Control in Non-responsive Celiac Disease Patients
Presenting Author: Caitlin Barrett

At BIDMC, we evaluated Viokace, a pancreatic enzyme supplement (PES), as a new treatment option for patients with Non-Responsive Celiac Disease (NRCD). In total 12 adult subjects with biopsy confirmed celiac disease and persistent symptoms despite 12 months on a gluten-free diet participated in the randomized, double-blind cross-over study. All subjects were randomized and received two treatment phases consisting of 10 days of Viokace PES treatment and 10 days of placebo treatment. Omeprazole 20 mg/ day was co-administered for the entire study. Our subject cohort did not see significant improvement in GI symptoms while on Viokace PES treatment. During run-in when patients only received Omeprazole, 9/12 of the subjects did see an improvement in abdominal pain, nausea, heartburn and acid reflux symptoms. This result may be indicative of need for a “trial of effect” of Omeprazole on a NRCD cohort.   To characterize the clinical effectiveness of pancreatic enzyme supplementation, future trials will require a larger sample size, wider range of symptom severity, and improved measures of pancreatic exocrine function.

The Gut Microbiota in Celiac Disease and Probiotics
Presenting author: Richa Chibbar, MD

The gut microbiome is established early in life, by age two.  It has many functions including regulating the immune system. Dysbiosis, or imbalance between protective and harmful bacterial species has been implicated in gastrointestinal disorders, such as inflammatory bowel disease.  This is thought to also play a role in the development of celiac disease.  Many factors can alter the gut microbiome, such as genetic predisposition, antibiotic exposure, and diet.  Gluten-free diets only partially restore the gut microbiome back to normal. 

Certain bacterial species have demonstrated a protective effect, such as Bifidobacterium spp and Lactobacillus spp, and, thus, it is thought that probiotics might have a benefit in celiac disease.  Certain strains can make gluten less toxic, while others reduce intestinal permeability and production of proinflammatory cytokines. 

This work was recently accepted for publication. To read the full article:
Chibbar R, Dieleman, LA. The Gut Microbiota in Celiac Disease and Probiotics. Nutrients 2019, 11, 2375.

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