May 18-21, San Diego. Research summaries
GIG’s Education Supervisor, Lola O’Rourke MS, RDN, recently attended the 50th anniversary Digestive Disease Week (DDW) conference in San Diego and has compiled an impressive list of summaries of the latest research on celiac disease, non-celiac gluten sensitivity, and gluten-related disorders. Be sure to check these out to stay up to date on the newest research in the field!
“UTILITY OF SYMPTOM SEVERITY, FREQUENCY, AND LABILITY IN PREDICTING SEROLOGY STATUS AND VILLOUS INJURY IN SYMPTOMATIC ADULTS WITH TREATED CELIAC DISEASE”
Authors: Adam Bledsoe, Jack Syage, Katherine King, Tsung-Teh Wu, Joseph Murray
Symptoms alone are not enough for indicating whether intestinal healing has occurred in celiac disease patients who are on a gluten-free diet.
This study aimed to assess whether symptom frequency and lability (changeability) in celiac disease patients could predict intestinal damage and CD antibody levels. As background, it was noted that after one year approximately 55% of CD patients show villous improvement, and after 5 years, approximately 85% do, leaving a significant portion not showing the desired improvement. The study looked at data on symptoms, biopsies and CD antibody results of 1276 CD patients. The average age was 47, and about 20% were male. Factors evaluated included proportion of days with tiredness, proportion of days with bloating, and overall mean symptom score (assessed using a standard Celiac Disease Symptom Diary).Results showed that symptoms were inconsistent in terms of predicting objective measures of celiac disease control (improvement in intestinal damage or CD antibody levels). The authors note that their findings reinforce the importance of clinicians not relying just on symptoms when assessing patients’ response to a gluten-free diet. Since diarrhea was the only symptom that did show an association with intestinal cell damage, this symptom is one which should prompt clinicians to consider re-evaluating status of intestinal recovery. Other symptom severity, frequency and lability did not predict intestinal damage.
presented by Juan Stefanolo
Authors: Juan Pablo Stefanolo, Martín Tálamo, Samanta Dodds, Emilia Sugai, Paz Temprano, Ana Costa, María Laura Moreno, María Inés Pinto Sanchez, Edgardo Smecuol, Horacio Vázquez, Andrea Fabiana Gonzalez, Sonia Isabel Niveloni, Elena Francisca Verdu, Eduardo Mauriño, Julio C. Bai
Testing finds that celiac disease patients are frequently exposed to gluten contamination, and whether or not they had symptoms had no correlation with the level of contamination experienced.
Background: patients with CD who are on a gluten-free diet are often exposed to gluten contamination, and it is unknown how frequently this occurs in real life settings. This research explored the pattern of urinary and fecal excretion of gluten immunogenic peptide (GIP) during a 4 week period in CD patients who had been on a gluten-free diet for more than two years. At the beginning of the study patients completed a celiac symptom index (CSI) questionnaire to determine presence of symptoms. Patients collected samples that would reflect both weekday and weekend food intake. Results showed that 96% of cases had transgressions at least once during the 4 week period. 91% had transgressions during weekends, and 48% during week-days. There was no difference between symptomatic and asymptomatic individuals, and there was no correlation between transgressions and symptoms. The authors concluded that there is a high frequency of dietary transgressions in CD patients who are on a long-term GFD, whether or not they have symptoms, and that ingestion of gluten was more common on weekends.
Authors: Randi L. Wolf, Mary Morawetz, Anne R. Lee, Pamela A. Koch, Isobel R. Contento, Peter H. R. Green, Benjamin Lebwohl
Participation in cooking class improves quality of life for celiac disease patients.
As background, it is noted that few studies have addressed mechanisms for encouraging adherence to a GFD for those with CD. The aim of this pilot study was to determine whether an innovative cooking intervention could improve adherence to the gluten-free diet (GFD) and quality of life in individuals with CD. 12 adults (aged 18-70) were enrolled, and participated in two 4.5 hour sessions. Goals were to increase home-cooked meals with naturally GF proteins and whole grains, and increase nutrient dense snacks from whole grains, nuts, and seeds. Each of the following were measured at the beginning of the study, and again after completion: CD-specific quality of life; symptoms, diet adherence, depression, and anxiety. After the one month period, participants had significant positive outcomes: greater dietary adherence, improved quality of life, and lower depression and anxiety scores. The authors conclude that this approach warrants further investigation in a larger controlled study.
Authors: Edgardo Smecuol, Paz Temprano, Ana Costa, Emilia Sugai, María Laura Moreno, María Inés Pinto Sanchez, Horacio Vázquez, Juan Pablo Stefanolo, Andrea Fabiana Gonzalez, Christopher R. D’Adamo, Sonia Isabel Niveloni, Elena Francisca Verdu, Eduardo Mauriño, Julio C. Bai, Dr. C. Bonorino
Probiotic alleviates symptoms in some celiac disease patients.
As background it is noted that 30-50% of treated CD patients have persistent or relapsing GI symptoms despite apparent compliance with the GFD. Also, that a recent trial showed that oral administration of the probiotic Bifidobacterium infantis NLS-SS alleviated symptoms in newly diagnosed CD patients consuming gluten and that this effect could be attributed to the modulation of innate immunity. The aim of this study was to explore the effects of a 3 week course of Bifidobacterium infantis NLS-SS on CD patients with persistent symptoms. 18 adult patients were enrolled who had been on a GFD for at least two years and were symptomatic according to a GI symptoms rating score. Patients were divided into two groups, with one receiving the B. Infantis, and the other receiving placebo. After a “wash out” period, patients then switched treatments. Results led the authors to conclude that B infantis may improve specific CD symptoms on a GFD in patients who have a higher symptomatic burden. Additional larger studies are called for to further investigate this effect.
Authors: Muhammad Akrmah, Mohammed Ubaid Alsaggaf, Maryam R Hussain
No connection found between antibiotic exposure during pregnancy and development of celiac disease in offspring.
Background: Infections and use of antibiotics are common during pregnancy and may affect fetal development and autoimmunity. This research aimed to assess the evidence of a relationship between antibiotic exposure during pregnancy and celiac disease development in the offspring. A comprehensive review and meta-analysis was done of relevant studies published between 1948 and 2018. Only 3 studies qualified for inclusion in the final analysis. This meta-analysis did not suggest any association between antibiotic exposure during pregnancy and increased risk of celiac disease in childhood. The authors note, however, that additional future research is needed to study this potential association.
Authors: Natalie J. Patel, Amporn Atsawarungruangkit, Daniel A. Leffler, John A. Hart, Andrea Olivas, Michael Vieth, Balint Melcher, Abdulbaqi Al-toma, Chris J.J. Mulder, Marcela A. Salomao, Rish Pai, Mary P. Bronner, Mariana Moreno Prats, Bita V. Naini, Cherise Meyerson, Luca Elli, Alessandro del Gobbo, Sanjay Kakar, Won-Tak Choi, Purva Gopal, Maria Westerhoff, Jerome Cheng, Marie Robert
No connection found between either symptoms or lab tests and persistence of intestinal damage in celiac disease individuals on a gluten-free diet.
Lack of complete intestinal healing in celiac disease is not uncommon, despite adherence to a gluten-free diet. These researchers aimed to define factors associated with mucosal healing and persistent villous atrophy, in order to better classify and identify populations which may benefit from additional therapies, and to evaluate the role of repeat biopsy. 214 paired biopsies (initial and repeat) were obtained from 107 patients; mean time between initial and repeat biopsy was 2.4 years. Other factors assessed included symptoms, CD antibody levels, dietary adherence, and medications. Overall, no statistical difference was found between the incidence of specific symptoms and persistence of intestinal damage. The authors concluded that common laboratory tests, and signs and symptoms of celiac disease do not reliably predict duodenal mucosal healing at re-biopsy, that blunting of intestinal cells may be present in spite of clinical improvement, and that their findings support the need for assessment of mucosal healing in celiac disease.
Authors: Jennifer Ann Sealey Voyksner, Joseph A. Murray, Chaitan Khosla, Matthew A. Dickason, Jack Albert Syage
Potential new, non-invasive method for assessing intestinal cell recovery in celiac disease patients.
Background. Newly diagnosed patients with celiac disease have intestinal damage that may recover over time on a GF diet. The only currently accepted way to monitor the health of intestinal cells of CD patients is to do an intrusive and expensive biopsy. Simvastatin (SV) is a commonly used medication whose metabolism is tied in with a substance on the villi of the small intestine; therefore its rate of metabolism can reflect the rate at which a patient’s villi are healing. These researchers developed a way to measure the metabolic rate of SV in a patient’s blood.The study included 20 newly diagnosed CD patients, 10 long term treated CD patients, and 10 non-CD controls, over 12 months. SV was administered to the patients at 0, 6, and 12 month visits, and blood was drawn at 5 time points. Results showed the expected trend of high values for newly diagnosed CD patients, low values for healthy non-CD controls, and intermediate values for long-term treated CD patients. These results support the feasibility of SV being used as a diagnostic tool that is minimally invasive and economical, to monitor intestinal cell recovery in CD patients. Research in this area is continuing.
“LATIGLUTENASE IMPROVES QUALITY OF LIFE IN SEROPOSITIVE CELIAC DISEASE PATIENTS”
Authors: Jack Syage, Daniel Adelman, Joseph Murray, Jennifer Sealey Voyksner
Potential new treatment to counteract gluten exposure in celiac disease shows promising results; research is ongoing.
Latiglutenase is a substance designed to degrade gluten, that is intended for use in addition to (not as a replacement for) a gluten-free diet. Testing of the product is currently in process. The following are the results of the Phase 2b trial. (Phase 2 trials are the second step in testing an experimental treatment.) Moderately to severely symptomatic CD patients were enrolled who reported adhering to a GF diet for at least a year. Even though they reported adhering to the GF diet, they were considered to be inadvertently ingesting gluten because of reported symptoms and evidence of villous atrophy. Approximately 400 patients completed the 12 week study, which included 5 different dosage levels of latiglutenase. Patients with both positive and negative CD antibody results were included. Quality of life and symptoms were measured at 0, 6, and 12 weeks. The researchers conclude that their data demonstrate that seropositive patients experienced significant improvement in quality of life when given a high dose of latiglutenase, and that the improvements strongly correlate with symptom improvement. An NIH-funded trial at the Mayo clinic will further evaluate quality of life and symptom relief as outcome measures in a gluten-challenge study on diagnosed CD patients.
“ADHERENCE TO THE GLUTEN-FREE DIET AND CELIAC DISEASE PATIENT OUTCOMES: REAL WORLD EVIDENCES FROM AN INTERNATIONAL PATIENT REGISTRY, ICURECELIAC”
Authors: Jennifer Drahos, Kaili Ren, Marilyn Geller, Song Wang, Daniel Leffler
Celiac patients tend to believe they are adhering to the gluten-free diet better than they are; half are not adhering sufficiently.
This study aimed to evaluate gluten-free diet (GFD) adherence in CD patients, and its association with patient outcomes. Patient information was collected through iCureCeliacTM , a patient registry hosted by the Celiac Disease Foundation. Online surveys collected demographics, disease characteristics, diagnostic journey, and outcomes. Adherence to the GFD was measured by a stand-alone question and by a standard “Celiac Dietary Adherence Test” (CDAT). CD symptom burden and quality of life were also assessed using standardized methods.The analysis of 522 respondents showed that half (50.2%) had sufficient GFD adherence based on CDAT scores, compared with 96.4% claiming as “always” or “often” keeping a strict GFD. Quality of Life measures were significantly higher in those with well-controlled disease compared to those with high symptom burden. The authors conclude that: 1) self-perceived adherence to a GFD can be misleading, as it almost doubles the adherence that is measured by a validated instrument, 2) half of CD patients cannot sufficiently adhere to the GFD, 3) symptom burden is strongly correlated with lower quality of life, 4) despite adherence to a GFD, many patients still have persistent or high symptom burden and reduced quality of life. The authors conclude that their evidence suggests that adhering to a GFD is not universally effective and that there are significant unmet medical needs for better treatment options.
“IS THE INCREASE IN CELIAC DISEASE INCIDENCE DUE TO A BIRTH COHORT OR TIME PERIOD EFFECT?: A POPULATION BASED STUDY”
Authors: Rok Seon Choung, Alberto Rubio-Tapia, Eric Marietta, Katherine King, Joseph Larson, Imad Absah, Joseph Murray
Since 1995, there has been an increased incidence of celiac disease in all age groups, suggesting that environmental factors are likely responsible.
The authors note that the incidence of CD is increasing in the U.S., but that the reason for this trend is unknown. They aimed to assess whether the rise was related to a birth cohort (group), or whether the increase occurred during a specific time period independent of age and birth cohort. The Rochester Epidemiology Project (REP), a medical records linkage system in Olmsted County, Minnesota, was used to identify newly diagnosed cases of CD from 1966 to 2015. Incidence rates were standardized to the U.S. population. During this time period 474 patients were diagnosed with CD. There was an increase in CD diagnosis after 1995 independent of age and birth cohort. From 1966 to 1995, the adjusted CD incidence was consistently low; but from 1996 to 2015 it increased markedly among residents of virtually all age groups (except those in the extremes of less than 10 or greater than 80). The authors conclude that their data suggests that the increase in CD in their Midwestern U.S. community represents a time period effect that started in the mid 1990’s, that is independent of age and birth cohort, and that this increase can’t be explained by factors affecting early childhood only. Rather, they state that an environmental factor(s) that impacted all ages likely underlies the recent increase in CD.
“THE POSITIVE AND NEGATIVE RIPPLE-EFFECT OF CELIAC DISEASE DIAGNOSIS AND MANAGEMENT ON THE FAMILY: A MIXED METHODS APPROACH”
Authors: Carrie Russo, Benjamin Lebwohl, Anne Lee, Norelle Reilly, Patricia Zybert, Peter H. Green, Randi Wolf
Both positive and negative effects of a celiac diagnosis on other family members should be considered for maximizing quality of life for kids with celiac disease.
A CD diagnosis can have repercussions for the entire family, but little is known about this potential “ripple-effect” of CD diagnosis and management. The authors aimed to qualitatively and qualitatively describe these effects on family members. Sixteen families were recruited who had a child (aged 8 to 18) with confirmed CD. Measures were made of diet adherence, quality of life, and other factors, including parents’ level of concern about their child’s health, burden in caring for their child’s dietary needs, and level of change in various aspects of their life following diagnosis.Children rated their own quality of life as well, and interviews were also conducted with siblings. All children in the study were considered to have high GFD adherence. Mothers’ and fathers’ ratings of how their child’s CD diagnosis affected their lifestyle, social life, and level of burden in caring for their child’s dietary needs differed significantly, with mother reporting more change and burden.Themes that emerged related to a negative “ripple effect” included burden of taking on the majority of food tasks (mothers), feeling of guilt for carrying a CD-associated gene and limited restaurant choices for the family (fathers), and feeling annoyed by having to unnecessarily limit certain foods at home (siblings). Themes related to a positive “ripple-effect” included becoming more creative cooks (mothers), incorporation of new family traditions (fathers), and developing empathy for others (siblings). The researchers conclude that substantial “ripple-effects” were found and that including parents and siblings in research provides insight into the entire family experience and can help inform family-centered interventions on how to maximize quality of life for everyone impacted by a child’s diagnosis of CD.
“CELIAC AUTOIMMUNITY AND PREGNANCY OUTCOMES”
Authors: Melis Gokce Celdir, Rok Seon Choung, Shahryar Khaleghi Rostamkolaei, Katherine S. King, Joseph J. Larson, Imad Absah, Joseph A. Murray
Women with positive celiac disease antibody tests have higher rates of low birth weight infants, but otherwise have similar reproductive characteristics as women without positive CD antibodies.
This research aimed to evaluate reproductive outcomes in women with CD autoimmunity from a community-based population, compared to age-matched healthy controls. Subjects had tested positive for CD serology between 2006 and 2011. Reproductive characteristics of the women and outcomes of single birth pregnancies were compared. 179 seropositive females, and 440 seronegative (without a prior CD diagnosis) were included. In this study, it was found that women with CD autoimmunity appeared to have similar reproductive characteristics but higher rates of deliveries of low birth weight infants compared to controls. The authors conclude that further studies on the effect of CD autoimmunity and of CD diagnosis with treatment in women of reproductive age are warranted.
Authors: James King, Jocelyn Jeong, Fox Underwood, Joshua Quan, Nicola Panaccione, Joseph Windsor, Stephanie Coward, Jennifer deBruyn, Paul Ronksley, Abdel Aziz Shaheen, Hude Quan, Jenny Godley, Sander Veldhuyzen van Zanten, Benjamin Lebwohl, Siew Ng, Gilaad Kaplan
Incidence of celiac disease has been rising among all age groups over the last few decades in many industrialized countries, affecting women and children the most.
The researchers sought to understand the incidence of CD in various regions of the world, as well as if and how this has changed over time. A literature search was done to identify all population-based studies (through July 19, 2018) reporting incidence of diagnosed celiac disease. 46 studies were deemed suitable for analysis, which were primarily based in Europe (38), with the remainder being based in North America (7) and Oceania (1). Overall incidence of CD was assessed in 19 studies, 19 focused exclusively on children, and 8 focused exclusively on adults. Findings led the authors to conclude that incidence of diagnosed celiac disease has been significantly rising among all age groups over the last few decades in many industrialized nations, that diagnoses of celiac disease continue to disproportionately affect females and children, and that population-based studies should be performed in Africa, Asia, and South America to provide a comprehensive picture in the global epidemiology of celiac disease diagnosis rates.
Authors: Paul Thomas Kroner, Alex Michael Kesler, Peter Abader, Mohammad Afsh, Bhaumik Brahmbhatt, Brian E. Lacy
Better diagnostic tests may explain increased celiac disease prevalence, and associated medical conditions may be the reason for increased medical costs.
This study looked at a sample of in-patient data from 2007 to 2016 in the U.S, which included all patients diagnosed with CD. A total of 337,201 patients were identified, with a mean age of 55.3 years; 71 % were female. In addition to determining inpatient prevalence of CD in the past decade, the study also set out to determine the most common reasons for GI (gastrointestinal) admission, inpatient mortality, morbidity (disease, or illness), length of hospital stay, total hospital charges and costs. Results showed that the inpatient prevalence of CD in the US increased from 2007 (52 cases per 100,000 admissions) to 2016 (117 cases per 100,000 admissions), and that the most common GI reasons for admission were acute pancreatitis, small bowel obstruction, diverticular disease, C. difficile infection and GI bleed. The authors conclude that the national inpatient prevalence of celiac disease has increased in the past decade, and that this may be the result of better diagnostic tests, rather than an absolute increase in overall prevalence. The increased hospital costs and charges which were found may be a reflection of increased prevalence of additional conditions that are more likely to occur in CD patients. Future additional studies are needed.
Authors: Pamela Kim, Hamza Arif, Kristen Suchniak-Mussari, Vincent Michael Pronesti, K.J. Shields, Curren Katz, Heitham Abdul-Baki
Multidisciplinary celiac disease centers (where nutrition, gastroenterology, and psychology clinics collaborate) may improve CD management compared to receiving care in a gastroenterology clinic.
A multidisciplinary approach to CD management has been proposed, but little data exists regarding the quality of care within multidisciplinary celiac disease centers (MCDC).This study aimed to compare quality of CD management in a MCDC with quality of CD management at a general gastroenterology clinic (GGIC), which were both within the same medical center. The MCDC is composed of collaborative Gastroenterology, Nutrition, Dietary, and Psychology clinics. 100 patient charts were randomly selected (60 MCDC, and 40 GGIC); 9 patients had to be excluded. Patients’ medical charts were reviewed. Demographic data and standard/recommended clinical data points were collected. Follow-up checks of CD antibody levels and appropriate management were significantly higher in the MCDC group. Both groups showed similar adherence to recommended endoscopic evaluation. Patients in the MCDC group received more counseling on related autoimmune conditions, NSAID (non-steroidal anti-inflammatory drugs) avoidance and risk of osteoporosis. They were also more up-to-date on osteoporosis screening, and micronutrient deficiencies were checked and addressed more within the MCDC groups. The authors conclude that this study confirms that the MCDC may improve adherence to guideline recommendations for CD management compared to GGIC. They note that further larger studies are needed to evaluate clinical patient outcomes.
Authors: Juan Sebastián Lasa, Astrid Rausch, Pablo Andres Olivera, Silvina Paz, Ignacio Zubiaurre
A significant portion of celiac patients don’t receive adequate follow-up care, and both patient-related and medical-related factors may be the cause.
Regular follow up visits to a physician are recommended as part of CD treatment, but it has been suggested that CD patients are not receiving adequate follow-up. The aim of this study was to describe the proportion of CD patients who comply with follow-up recommendations, and to describe the associated variables. 194 patients were enrolled from two centers in Buenos Aires, Argentina. Median age was 40, and 79.89% were female. Median time from diagnosis was 4 years. Self-reported adherence to the GF diet was inadequate in 14.94% of patients. Results showed that 44.84% of patients did not receive adequate follow up: 41.24% did not attend follow up visits regularly; 17.23% of those who are followed up by a physician did not have CD antibody tests or endoscopic evaluation done, and 48.45% had never been evaluated by a trained nutrition specialist. Factors related to adequate follow-up were: 1) satisfaction with gastroenterologist care on diagnosis, and 2) financial assistance for gluten-free related costs. The authors conclude that a significant proportion of CD patients are not adequately followed up, that inadequate follow-up was not associated with self-reported lack of adherence to the GF diet, and that both patient-related and medical-related factors may be subject to modification to improve follow-up of these patients.
“ASSESSMENT OF PARENTAL GLUTEN-FREE DIET KNOWLEDGE IN A MULTI-DISCIPLINARY CELIAC DISEASE CLINIC”
Authors: Vanessa Maltin Weisbrod, Benny Kerzner, Shayna Skelley Coburn, Joyana Peters McMahon, Catherine Raber, Blair M. Raber, Margaret Parker, Lori Stern, Ilana Kahn, Maegan Sady, William Suslovic, Kathleen Walters
Parents of kids with celiac disease are found to be lacking knowledge of the gluten-free diet, and need to receive more education when their kids are diagnosed.
As part of their effort to develop new educational tools for GF diet education, the authors set out to determine whether parents of children with CD are able to identify gluten-containing ingredients and correctly answer questions about labeling. Parents of diagnosed children who had been on a GF diet from one month to two years completed a questionnaire at this multi-disciplinary celiac disease clinic. Questions evaluated understanding of food labeling laws, labeling of medications and supplements and specifying whether a list of ingredients are “safe (gluten-free)” or “unsafe (contain gluten).” Parents were also asked about their confidence in understanding the gluten-free diet. 37 parents completed the survey. While 98.7% correctly identified wheat as a gluten-containing ingredient, some parents incorrectly classified several other gluten-containing grains as safe (including barley, rye, and spelt). Parents also incorrectly listed some GF ingredients as “unsafe”, including buckwheat and millet. The authors conclude that parents of children with celiac disease do not have accurate knowledge of ingredients and labeling laws needed to determine the gluten-free status of foods and medications, and are not aware of the gaps in their knowledge. This could lead to accidental gluten exposure or to unnecessary avoidance of gluten-free foods. Education interventions at the time of celiac disease diagnosis may help families better understand the requirements for managing a gluten-free diet.
Authors: Rok Seon Choung1, Irina E. Horwath1, Eric Marietta1, Joshua T. Bublitz2, Janet E. Olson3, Joseph A. Murray1
First degree relatives of people who have celiac disease have increased rates of celiac disease autoimmunity and of associated autoimmune diseases.
This study population consisted of 1064 individuals who had first degree relatives diagnosed with celiac disease (“FDR’s”) and 1064 controls, all of whom provided blood and survey data at time of enrollment and again 4 years later. The surveys included questions about personal and family history of CD, autoimmune diseases, malignancies, mental diseases, and gastrointestinal diseases. Results found that celiac FDRs had increased rates of autoimmune diseases, thyroid disease, and allergies; celiac FDRs did not have an increased risk for type 1 diabetes or asthma. Celiac FDRs were significantly associated with increased rates of gastrointestinal disease such as GERD, IBS, and liver diseases. Mental and musculoskeletal disorders like anxiety, depression, and fibromyalgia were also significantly frequent in celiac FDRs, compared to matched controls. However, celiac FDRs were not significantly associated with history of malignancies including lymphoma, leukemia, and type 2 diabetes.The authors conclude that the prevalence of CD autoimmunity in celiac FDRs is much higher as compared with controls. Celiac FDRs also had higher prevalence of other disease conditions known to co-occur with CD.
“PROSPECTIVE LONGITUDINAL GUT METAGENOMIC ANALYSIS SUGGESTS ALTERED MICROBIOME COMPOSITION AND FUNCTION IN INFANTS PRIOR TO CELIAC DISEASE ONSET”
Authors: Maureen Leonard, Poorani Subramanian, Francesco Valitutti, Gloria Serena, Victoria Kenyon, Stephanie Camhi, Pasquina Piemontese, Chiara Maria Trovato, Celeste Lidia Raguseo, Tiziana Passaro, Monica Montuori, Basilio Malamisura, Ruggero Francavilla, Luca Elli, Salvatore Cucchiara, Hiren Karathia, Rita Colwell, Nur Hasan, Alessio Fasano
Infants who later develop celiac disease are found to have an altered microbiome before CD occurs, suggesting that this may play a role in the development of celiac disease.
Factors necessary for development of CD are genetic predisposition, exposure to gluten, and environmental factors/triggers. One such environmental factor is an individual’s microbiome. Some studies have found an altered microbiome in patients with CD, but it is unclear whether these alteration occur before or after the onset of CD. These researchers looked at a group of infants who were at-risk of CD, to investigate whether infants that develop CD have an altered intestinal microbiome composition and function before they lose tolerance to gluten and develop CD. Differences in the abundance of microbial species between the infants at risk of CD and infants who were not at-risk for CD were identified as early as 12 months before the onset of CD.The authors conclude that their findings suggest a potential role of microbial alteration in CD development.
Authors: Jehad Almasri, Mohammad Murad, Katherine King, Mhd Louai Manini, Imad Absah
Neither antibiotic use during pregnancy nor delivery mode (vaginal vs. C-section) was associated with increased risk of autoimmune disorders such as celiac disease or autism spectrum disorder.
The authors note as background: 1) use of antibiotics during the last week of pregnancy and/or during delivery is increasing, 2) incidence of autoimmune disorders (such as CD) and autistic spectrum disorders (ASD) is increasing worldwide, and 3) an association between the two is therefore possible since antibiotic exposure may lead to a perturbation in the neonatal microbiome and may negatively affect the developing immune system. The researchers aimed to investigate this association and also to explore the association between delivery mode (vaginal vs. C section) and autoimmune diseases and ASD. 242 cases (69 CD, 13 Irritable Bowel Disease, and 164 ASD) and 484 matched controls were included in the study. The median age at last follow-up was 11.3 years (range 0.5-14.9). Among the included 726 births, 62% had vaginal delivery without antibiotics exposure, 13% had vaginal delivery with antibiotics exposure and 25% had Cesarean section delivery. The authors conclude that in this study group there was no association between peripartum antibiotics exposure or the mode of delivery and developing CD or ASD, and that future research about the etiology of these complex disorders is needed.
Presenter: Alessio Fasano
Non-celiac gluten sensitivity remains poorly defined, but it is recognized as a distinct condition with an estimated prevalence of between 0.5 and 13%.
While non-celiac gluten sensitivity (NCGS) still remains poorly defined and understood, it is a distinct gluten-related condition, with estimated prevalence of between 0.5 & 13%.The intestinal damage that is characteristic of CD is not seen in NCGS, but increased intestinal permeability is involved, and some restructuring of intestinal cells has been seen in cell cultures of NCGS patients. NCGS is thought to involve an innate immune response, while CD involves both an innate and an adaptive (autoimmune) immune response. In CD, both the gliadin and glutenin portions of gluten are toxic; it is unknown whether this is also the case in NCGS. Since another component of wheat – amylase tryptin inhibitors (ATI’s) – also stimulates innate immunity, the terminology “non celiac wheat sensitivity” (NWGS) is sometimes used instead of NCGS. Other components of gluten-containing foods such as FODMAPs may also be involved in NCGS. It is also unknown whether individuals with NCGS must adhere as strictly to the GF diet as those with CD: those with CD must keep intake to < 10 mg/day; levels for NCGS are unknown. It is also unknown whether there is increased risk of other disease associated with NCGS. NCGS most likely exists, but is still poorly defined due to lack of validated biomarkers that are instrumental for diagnosis, and for definitely establishing its prevalence. Research into NCGS is where CD research was approximately 30-40 years ago; stay tuned for advances in understanding.
Authors: Brad Palanski, Andrew Hilmer, Nielson Weng, Lichao Zhang, Lalla Fall, Joshua Elias, Nielsen Fernandez-Becker, Chaitan Khosla
Progress made on potential future biomarker of celiac disease in urine.
This research sought to determine whether peptides (protein fragments) from dietary gluten could be detected in human urine, and whether there were differences in the peptides detected in celiac disease patients compared to healthy controls. It was found that urinary gluten peptidomes (a peptidome is a set of peptides) of healthy volunteers and patients with celiac disease did have different biological and chemical properties. The researchers are continuing their work to evaluate the potential use of peptides detected according to their method, as a non-invasive biomarker of celiac disease status.
Authors: Geethanjali Pickert, Johannes Matzner, Sebastian Rosigkeit, Dorothe Thies, Rosario Heck, Detlef Schuppan
Component of wheat other than gluten is found to cause inflammation, supporting potential role in CD and other autoimmune/inflammatory diseases.
As background, the question exists regarding whether components of gluten-containing grains other than (or in addition to) gluten may be involved in causing adverse effects in both people with celiac disease and non-celiac gluten sensitivity. One such substance is wheat amylase-trypsin inhibitors (ATI’s). These researchers note that ATI’s have been implicated as promoters of celiac disease and other autoimmune/inflammatory diseases. Their research aimed to characterize the effect of these ATI’s on the distribution of certain types of cells in various organs, and on signaling pathways. Their results showed that diets containing ATI’s caused low-level systemic inflammation.
Authors: Alberto Caminero Fernandez, Justin McCarville, Victor Zevallos, Marc Pigrau, Bella Yu, Jennifer Jury, Heather Galipeau, Javier Casqueiro, Joseph Murray, Stephen Collins, Armin Alaedini, Premysl Bercik, Detlef Schuppan, Elena Verdu
The non-gluten protein family of ATI’s (amylase trypsin inhibitors) in wheat is found to play a role in GI diseases. Specific microbial strains which degrade ATI’s can be developed for use in treatment.
Amylase trypsin inhibitors (ATI) in wheat cause innate immune responses and are also thought to be involved in inflammation and allergies. This research aimed to investigate the role of ATI in gut barrier dysfunction and dysmotility in mice with and without celiac disease risk genes, and also looked at the ability of core microbial groups to degrade ATI and prevent gut dysfunction. The results led the researchers to conclude that the non-gluten protein family of ATI may play a role in other gastrointestinal diseases, and that microbiome-modulating strategies based on the use of microbial strains with specific ATI-degrading capacity can be developed to treat patients with wheat-sensitivity disorders.
Authors Randi L. Wolf, Peter H. R. Green, Anne R. Lee, Norelle Rizkalla Reilly, Patricia Zybert, Benjamin Lebwohl
Portable gluten sensor found to have mixed results for people with celiac disease: leads to some anxiety in teens; may improve quality of life for adults.
This research aimed to assess how individuals with CD use a handheld gluten detecting device (Nima), and to identify associated benefits and barriers. The study included 30 individuals with CD, aged 13-70. Participants were assigned either low, medium, or high numbers of single-use capsules for their device. Participants were assessed for celiac disease specific quality of life (CDQOL), symptoms (CDSD), diet adherence (CDAT), depression (CES-D), and anxiety (STAI) at baseline and then again three months after the study. Patients’ opinions on their experiences were also collected. At 3 month follow-up, adults had significantly improved CDQOL scores, and CES-D scores, but no changes in other variables.Teenagers exhibited no changes in adherence or symptoms. The number of capsules assigned was not associated with differences in outcomes. There was agreement that the device was helpful and that participants would continue using it for select occasions, but also that capsules were difficult to close and testing time consuming. Although anxiety was not reported to be a major barrier by either group, teenagers were more likely than adults to report feeling anxiety when using Nima. The authors note that portable gluten sensors may have utility for improving CD-specific QOL and depression among adults. Future studies should investigate long-term effects on QOL and on indicators of clinical outcomes such as mucosal healing. Patients need to better understand the device’s limitations.
Authors: Amanda Katherine Cartee, Katherine S. King, Suyue Wang, John L. Dzuris, Robert P. Anderson, Carol T. Van Dyke, Chadrick A. Hinson, Eric Marietta, Rok Seon Choung, David A. Katzka, Vandana Nehra, Madhusudan Grover, Joseph A. Murray
In patients with either celiac disease or gluten sensitivity, symptoms alone did not differentiate those who had ingested gluten from those who had not. The CD patients who had ingested gluten showed an increased blood level of a substance released by gluten-specific T-cells, and this increase correlated with their symptoms.
This study aimed to determine: 1) if CD and NCGS subjects develop symptoms after gluten exposure, 2) if CD and NCGS subjects are able to accurately determine if they received gluten, and 3) if serum IL-2 (a substance released by gluten-specific T-cells upon activation by gluten) levels distinguish CD from NCGS and healthy subjects when receiving gluten. There were 60 subjects: 20 with CD, 20 with NCGS, and 20 controls. Subjects were blindly given either gluten or placebo – i.e. they did not know which they had received. CD and NCGS subjects tended to report more symptoms than control subjects. Nausea and abdominal pain were the most common in CD subjects; fatigue and bloating were also reported; median symptom onset occurred at 2.5 hours. NCGS-gluten subjects reported bloating, fatigue, nausea, and abdominal pain; median symptom onset was 0.5 hours. There was no difference in the symptoms reported in the gluten or placebo arms of both the CD and NCGS groups. Only 2 CD and 4 NCGS subjects correctly identified gluten exposure. A significant rise in serum IL-2 levels occurred only in the CD-gluten group. Levels typically peaked at 3 hours and returned to baseline by 24 hours after the gluten challenge, correlating with symptom onset in CD-gluten subjects. The authors concluded: 1) an acute rise in serum IL-2 differentiated CD-gluten subjects from the CD-placebo, NCGS, and control subjects, 2) that the IL-2 peak and duration correlated with the median symptom onset, suggesting rapid onset activation of T cells by gluten even after a one-time gluten exposure on a longstanding gluten-free diet, and 3) that gluten-specific T cells are unlikely to be involved in the pathogenesis of NCGS.
Authors: Michael D.E. Potter, Michael P. Jones, Marjorie Mary Walker, Simon Keely, Natasha A. Koloski, Gerald J. Holtmann, Nicholas J. Talley
Avoidance of gluten in an Australian population group was found to be stable from 2015 to 2018, with a prevalence of about 13%. General health was the most common reason for avoidance.
The authors state that self-reported non-celiac wheat sensitivity (SR-NCWS) is increasingly popular, with an estimated worldwide prevalence of approximately 10%, although there are no published data on this. In this study they aimed to evaluate the incidence of SR-NCWS over a 3 year period in a general population cohort in Australia. 1322 participants returned completed surveys. The prevalence of SR-NCWS in 2015 was 13.8%, and in 2018 was 13.5%. The most common symptoms associated with gluten ingestion included bloating (80%), abdominal swelling (52%) and fatigue (33%).The prevalence of celiac disease was 1%, however 24% of the population were partially or completely avoiding gluten. Reasons cited for avoidance included general health (57%), abdominal symptoms (45%) and weight loss (34%). The risk factors associated with gluten avoidance included physician diagnosed food allergy, adherence to another specialized diet, and SR-NCWS. The authors conclude that the prevalence of SR-NCWS was stable over a 3-year period, and that the prevalence of gluten avoidance is high, with general health being the most common reason for avoidance.