Digestive Disease Week (DDW) 2020

Published September 29, 2020

GIG Research Update

The 2020 Digestive Disease Week (DDW) conference was cancelled due to the coronavirus pandemic, but there was still much to be learned from abstracts that had already been submitted and accepted. Following are summaries of selected abstracts related to celiac disease and gluten sensitivity.

Probiotics for celiac disease symptoms: research continues

PROBIOTICS FOR CELIAC DISEASE: A SYSTEMATIC REVIEW AND META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS

Authors: Seiler C et al.

Despite adherence to a gluten-free diet, many celiac disease patients still experience symptoms which may be mediated by the gut microbiota. Therefore, different studies have assessed the use of probiotics as an additional treatment for celiac disease. These researchers performed a systematic review and meta-analysis to evaluate the efficacy of probiotics in improving gastrointestinal symptoms and quality of life in patients with celiac disease. Seven articles with a total of 279 participants were eligible for this analysis. Some patients experienced improvement of gastrointestinal symptoms after a minimum of two weeks of supplementation with a probiotic. The authors note, however, that the overall quality of the evidence ranged from low to very low, and that further large clinical trials with a more rigorous design are needed to improve the quality of the evidence on this subject.

Research finds reduced exercise capacity in celiac patients

INCREASED ENERGY EXPENDITURE AND REDUCED EXERCISE CAPACITY SUGGESTS IMPAIRED NUTRITIONAL STATUS IN CELIAC DISEASE PATIENTS ON A GLUTEN FREE DIET

Authors: Colins AW et al.

Celiac disease patients often exhibit impaired nutritional status due to nutrient malabsorption and altered metabolism. These authors aimed to assess the use of exercise capacity testing to measure exercise-related energy utilization and exercise capacity in celiac patients compared to patients with other gastrointestinal conditions. Resting energy expenditure was estimated, along with exercise capacity and energy requirements at baseline, during minimal, moderate, and maximum exercise. During maximum exercise, energy expenditure was significantly greater in celiac patients, and exercise capacity in celiac patients was reduced compared to what was predicted. It was concluded that these findings are suggestive of chronic impaired nutritional status in treated celiac disease patients, and that there is a need for proper nutritional and functional capacity assessments in the follow-up of celiac patients.

Celiac patients more likely to experience anxiety, depression, and other psychiatric conditions

EPIDEMIOLOGY AND PREVALENCE OF PSYCHIATRIC DISEASES IN CELIAC DISEASE IN THE US: A POPULATION BASED STUDY

Authors: Alkhayyat M et al.

The database studied included over 30,000,000 individuals.  Of these, 980 had celiac disease. Prevalence of various psychiatric diseases among celiac patients was analyzed.   When compared to patients with no history of celiac disease (CD), patients with CD were more likely to have a history of anxiety, depression, bipolar, eating disorder and childhood onset autistic disorder. Patients with celiac disease and psychiatric conditions were more likely to be young adults (18-24 years old). The prevalence of anxiety, depression and eating disorders were more common in females, while bipolar, ADHD and autism were more common in males. Patients with celiac disease and psychiatric conditions were more likely to be smokers, with history of alcohol and substance abuse and with history of personality disorder. The authors conclude that special care and appropriate referral to psychiatry are warranted while dealing with this group of patients, and that further studies are needed to further delineate the risks and outcomes of celiac disease patients who have accompanying psychiatric conditions.

Promising research on potential celiac disease treatment

TAK-101 (TIMP-GLIA) PREVENTS GLUTEN CHALLENGE INDUCED IMMUNE ACTIVATION IN ADULTS WITH CELIAC DISEASE

Authors: Kelly CP et al.

TAK-101 is a substance being studied that would induce gluten tolerance in people with celiac disease. This Phase 2* study was designed to assess its safety and efficacy. There were two groups of patients: one given TAK-101 and one given a placebo, followed in each case by a gluten challenge. The two outcomes assessed were immune activation and intestinal damage. Promising results showed that this substance did prevent gluten challenge-induced immune activation in adults with celiac disease in this study. Additional studies are expected. (*New drugs/treatments go through 3 Phases of clinical trials before application is made to the FDA for approval.)

KUMA062 EFFECTIVELY DIGESTS GLUTEN IN THE HUMAN STOMACH: RESULTS OF A PHASE 1 STUDY

Authors: Pultz IS et al.

The aim of this study was to evaluate a substance (“Kuma062”) designed to degrade gluten, looking specifically at: safety, tolerability, and efficacy to degrade gluten below levels that trigger an immune response. 47 adults were enrolled. Results showed that the substance degraded immunogenic gliadin* fractions in the human stomach in physiologically relevant timeframes, suggesting that it may be a promising oral therapeutic. Further studies are warranted. (*Gliadin is a component of gluten.)

Can development of celiac disease be predicted?

IMMUNE RECOGNITION OF EPITOPES DERIVED FROM GLIADINS AND TISSUE TRANSLGUTAMINASE PRECEDE TTG-IGA POSITIVITY IN PEOPLE WHO DEVELOP CELIAC DISEASE 

Authors: Choung RS et al.

The aim of this study was to see if individuals who were later diagnosed with celiac disease showed changes in immune reactivity before diagnosis. This approach could theoretically be used in other patient populations to predict development of celiac disease, which would be beneficial because earlier detection could prevent irreversible negative consequences of the disease.  Blood samples of 159 young adults were included. The authors concluded that immune reactivity is present much earlier than the diagnosis of celiac disease, and that this can be used for predicting development of the disease. The authors note that research is needed to understand what triggers these changes and what factors amplify the immune reactions that contribute to the progression towards fully active celiac disease.

Celiac and pancreatic disease – is there a connection?

CELIAC DISEASE ASSOCIATED WITH HIGHER RISK OF PANCREATITIS: A META-ANALYSIS AND SYSTEMATIC REVIEW

Authors: Abureesh M et al.

The risk of pancreatitis in celiac disease patients has been reported in the scientific literature with conflicting data. These authors aimed to do a meta-analysis on the topic. Three studies with a total of nearly 109,145 patients with celiac disease were included.  1.26% had a diagnosis of acute pancreatitis, indicating that celiac patients do have a higher risk of acute pancreatitis.*The authors note that further research is needed to further evaluate the connection between these conditions.  (*Incidence of acute pancreatitis in the general population is in the range of .02%.)

Do gut microbes have an effect on persistent celiac symptoms?

SYMPTOMATIC AND ASYMPTOMATIC CELIAC DISEASE PATIENTS ON LONG-TERM GLUTEN-FREE DIET EXHIBIT DIFFERENCES IN FECAL MICROBIAL TAXA

Authors: Costa A et al.

A high proportion of celiac disease patients on a gluten-free diet continue to experience symptoms or relapses, and changes in the microbiota in the duodenum (the first part of the small intestine) have been suggested in association with such symptoms. These researchers aimed to correlate fecal microbiota of patients with the presence of gastrointestinal symptoms. Forty-four patients were enrolled, of which 19 (43.2%) were symptomatic despite being on a gluten-free diet. Overall fecal microbiota profiles overlapped between symptomatic and asymptomatic groups, however there were some differences, with types reported to contain protective bacteria (Lactobacillus and Bifidobacterium) decreased in symptomatic celiac patients on a gluten-free diet. The results suggest that microbial factors may contribute to persistence of symptoms in treated celiac disease.

Progress on identifying non-celiac gluten sensitivity

NON-CELIAC GLUTEN SENSITIVITY CAN BE DIFFERENTIATED FROM IRRITABLE BOWEL SYNDROME: A DIAGNOSTIC ALGORITHM

Authors: Barbaro MR et al.

The identification of a biomarker for non-celiac gluten sensitivity (NCGS) would help in establishing a diagnosis and in validating the condition. It can be difficult to distinguish NCGS from irritable bowel syndrome (IBS). The aim of this study was to investigate the role of serum zonulin (a protein that modulates intestinal permeability) as a diagnostic biomarker of NCGS. Study participants included 25 asymptomatic controls, 59 patients with IBS, 86 with NCGS, and 15 with celiac disease. Zonulin levels were measured. NCGS and CD patients had significantly increased zonulin levels compared to controls and IBS patients. Celiac disease can be excluded. The authors conclude that zonulin serum levels combined with demographic and clinical data can accurately differentiate non-celiac gluten sensitivity  from irritable bowel syndrome.

Celiac disease: malnourished and underweight, or obese? Things are changing

PREVALENCE OF OBESITY IN PATIENTS WITH CELIAC DISEASE OVER THE LAST 5 YEARS: A LARGE POPULATION DATABASE STUDY

Authors: Shah R, et al.

Historically, celiac disease was associated with weight loss, diarrhea, and malabsorption. Over recent years, however, it has been recognized that this is no longer the only or typical presentation of CD. These researchers aimed to assess whether the prevalence of obesity among patients with CD has increased, especially in light of the overall increased prevalence of obesity in the United States. An electronic health record database was searched that incorporated 26 healthcare systems and over 300 hospitals in the U.S. Patients with a diagnosis of celiac disease from 2014-2018 were considered. A total of 13,410 patients with CD were identified. Of these, a substantial number (6,040) were found to have a BMI (body mass index) greater than 30, which classifies as obese. These patients were further stratified according to standard levels of obesity: class I being the least obese, then class II, and class III being the most obese. Over these 5 years, prevalence of class I, II, and III obesity in celiac disease has continued to rise. The authors note that this study debunks a common misconception that celiac disease does not occur among obese individuals.

Parents of kids with celiac disease found to be in need of education

COMPARISON OF PARENTAL GLUTEN-FREE DIET KNOWLEDGE BETWEEN “NEW” AND “ESTABLISHED” DIAGNOSES IN A PEDIATRIC MULTIDISCIPLINARY CELIAC DISEASE CLINIC

Authors: Weisbrod VM, et al.

Parents of 80 children (ages 3-19) with celiac disease completed questionnaires regarding knowledge on various aspects of the gluten-free diet (GFD). Time on the GFD ranged from < 1 month to 11 years, with 56% being in the “new” diagnosis group (<3 months) and 44% in the “established” group (3 months or more). Most parents in both groups correctly identified some of the basic safe (corn, rice, tapioca) and unsafe (wheat, rye, barley) items. Both groups were poor at identifying farro as unsafe. Spelt was correctly identified as unsafe by significantly more parents in the established group, and similarly buckwheat and millet were correctly identified as gluten-free more often by parents in the established group. There was confusion in both groups about the FDA gluten-free labeling regulation, including almost one-third of parents believing that the cut-off level was “no” or < 5 ppm gluten (vs. the actual 20 ppm). The authors conclude that a sizable minority of parents of children with celiac disease have a gap in knowledge regarding the gluten-free diet. While parents of newly diagnosed kids were more likely to display knowledge gaps, there were also things that were poorly understood by parents of kids who had been diagnosed for years. These knowledge gaps underline the need for ongoing education regarding the gluten-free diet among celiac disease patients and families.

Does socioeconomic status influence likelihood of having celiac disease diagnosed?

AN INDIVIDUAL-HOUSING BASED SOCIOECONOMIC STATUS MEASURE PREDICTS DIAGNOSIS OF CELIAC DISEASE BUT NOT THE OCCURRENCE OF DISEASE

Authors: Choung RS, et al.

Incidence of celiac disease around the world is increasing, but the majority of those with the condition remain undiagnosed. These researchers looked at the effect of socioeconomic status (SES) on the detection of celiac disease. 387 patients in Olmstead County Minnesota who were diagnosed with celiac disease between 2000 and 2015 were identified, and were age and gender matched with a group of controls. A standard index was used to assess housing-based socioeconomic status. Results showed that adults with a high socioeconomic status in this U.S. community were more likely to be diagnosed with celiac disease, with the rate of diagnosis being 17% higher in the group of adults from the highest quartile of SES compared to those from the lowest quartile of SES. However, socioeconomic status was not related to occurrence of the disease. The authors note that increased implementation of diagnostic guidelines could result in better case identification among lower socioeconomic groups.

Is income associated with healing in celiac disease?

ASSOCIATION BETWEEN NEIGHBORHOOD INCOME AND PERSISTENT VILLOUS ATROPHY IN PATIENTS WITH CELIAC DISEASE UNDERGOING FOLLOW-UP BIOPSY

Authors: DeCuir N, et al.

Barriers to a gluten-free diet include high cost and limited availability of gluten-free substitute foods. These researchers hypothesized that mucosal healing rates in celiac disease may be higher among those who live in higher income neighborhoods. A retrospective study was done of patients 18 and over who had follow-up biopsies from March 2016 – October 2018 at a celiac disease center. Of the 977 patients with celiac disease, 789 (81%) had mucosal healing on repeat biopsy. Patients’ zip codes were correlated with income and divided into quartiles. Rates of healing were similar between all zip code groups. Rates of healing were similar for sex and race, but were greater in those of younger age and among those with a longer duration of CD at time of repeat biopsy (65% among those 0.5 to 1 year, 78% among those 1 to 2 years, 80% among those 2 to 5 years, 83% among those >5 years). Despite the economic burden of a gluten-free diet, mucosal healing rates were similar in adults with celiac disease at all neighborhood income groups in this group of patients. Future studies should investigate what other factors may be responsible for a lack of mucosal healing.

Organic pollutants and celiac disease: is there a connection?

ASSOCIATION BETWEEN PERSISTENT ORGANIC POLLUTANT EXPOSURE AND CELIAC DISEASE DIAGNOSIS IN CHILDREN

Authors: Gaylord A, et al.

Little is known about the environmental factors that may impact development of celiac disease in genetically susceptible populations. This research looked at exposure to persistent organic pollutants (POPs) as a possible related factor. 88 patients were recruited from the GI clinic of a New York hospital; of these, 30 had celiac disease. POP levels were analyzed among those with and without celiac disease. Age, race/ethnicity, BMI and hemoglobin did not differ significantly between the two groups. Controlling for sex, race, age, and genetic susceptibility score, patients with higher serum DDE (dichlorodiphenyldichloroethylene, which is a persistent organic pollutant) concentrations had 2-fold higher odds of celiac disease. This is the first study to report increased odds of celiac disease with POP exposure in children. These findings raise further questions of how environmental chemicals may affect autoimmunity in genetically susceptible individuals.

Celiac disease patients in China face many barriers

FACING THE UNKNOWN: NAVIGATING CELIAC DISEASE AND THE GLUTEN-FREE DIET IN CHINA

Authors: Zhang Q, et al.

Recent studies suggest that diagnosed cases of celiac disease (CD) in China may be “the tip of the iceberg.” Little is known about CD diagnosis and management in China. This pilot study aimed to quantitatively and qualitatively describe how individuals living in China navigate CD and the gluten-free diet (GFD). This was a pilot study of 17 individuals across 11 cities in Mainland China. Participants were adults or parents of young children with CD. In-depth interviews were conducted to assess CD-specific quality of life (QOL) and diet adherence (CDAT). Only 4 adults (30.8%) and 2 children (50.9%) had CDAT scores in the adequate range. QOL scores were also low. Themes that emerged included: (1) a challenging journey to diagnosis and treatment (e.g., lack of physician awareness about CD, use of traditional Chinese medicine that often made symptoms worse, lack of access to a dietitian and no follow-up care, reliance on doctors from the US for consultation), (2) lack of resources to maintain a gluten-free diet (GFD) (e.g., limited access to GF products and restaurants, overseas purchasing of GF foods and related high cost, reliance on online support groups for GFD advice), and (3) cultural and social barriers (e.g., belief that “eating noodles is good for better digestion,” social isolation due to lack of awareness about CD, belief that it is a “high-end” disease, only existing in the wealthy). Results suggest there is an urgent need for CD-specific education and Asian-adapted GFD guidance both among healthcare practitioners and patients. Given future initiatives to conduct population-wide screening for CD in China, efforts to promote CD management are critical.