Publications & Highlights
To further enhance your ability to obtain information of interest, the following member-submitted searches have been provided for you. The search was performed in the following databases: EMBASE, PubMed and Web of Science. The Web of Science platform provides access to the following products and databases: BIOSIS Previews; Journal Citation Reports; MEDLINE; SciELO Citation Index and Web of Science Core Collection.
Following the publications resources, you will find summaries written by NASSCD members about papers of interest.
NASSCD thanks Maria Ines Pinto Sanchez, MD, MSc and Heather Galipeau, PhD of the Farncombe Family Digestive Health Research Institute at McMaster University, Hamilton, ON, Canada for their oversight of this project. Their collaboration will provide updates to the Publications section of this site regularly and be shared with NASSCD members.
Please click on the category of interest for a listing of papers.
Clinical and Follow-Up papers
Gluten Free Diet and other Therapeutic Options
Microbiome, Metabolomics, Metagenomics
Systematic Reviews and Meta-analysis
Celiac Disease: Celiac Disease Research Results from MEDLINE/PubMed
Gluten Sensitivity: Gluten Sensitivity Research Results from MEDLINE/PubMed
HIGHLIGHT - PUBLICATION IN CLINICAL PRACTICEM Ines Pinto-Sanchez, MD, MSc
Commentary on: Fecal Gluten Peptides Reveal Limitations of Serological Tests and Food Questionnaires for Monitoring Gluten-Free Diet in Celiac Disease Patients. By Comino et al. Am J Gastroenterol 2016; 111:1456–1465.
The compliance with strict GFD is essential for patients with celiac disease (CD), not only for alleviation of symptoms, but also for the prevention of complications such as anemia, osteoporotic fractures and small-bowel lymphoma. However, many patients find the GFD difficult to follow, socially inconvenient and more expensive than a regular diet, leading to frequent contaminations or dietary transgressions. The adherence to GFD can be assessed by dietitian consultation, small bowel biopsy follow-up or specific CD serology. However, all the available methods have limitations and diagnostic tools to aid in the assessment of dietary compliance are needed.
Recently, a novel method detecting immunotoxic gluten peptides (GIPs) excreted in human feces has been proposed as a potential method to monitor the adherence to the GFD. Comino et al. performed a prospective, non-randomized, multicenter study including 188 patients with CD on GFD and 84 non-celiac healthy controls. Subjects recorded their intake in a dietary questionnaire and fecal GIP was quantified by enzyme-linked immunosorbent assay (ELISA). GIP measurements were correlated with serological anti-tissue transglutaminase (anti-tTG) IgA and anti-deamidated gliadin peptide (anti-DGP) IgA antibodies. The results showed that 30% of patients had detectable amounts of GIP in stool, suggesting that they were non-compliant with the diet. Interestingly, greater amounts of GIP were found in patients over 13 years of age and in those who were on GFD for longer period of time. Anti-DGP IgA, but not anti-tTG IgA, detected gluten ingestion, although the great majority of patients did not admit gluten transgression in the questionnaires. GIPs are excreted in feces only when gluten is ingested, thus detection in stools of patients with CD on GFD implies that there has been recent gluten exposure. Although this method could constitute a promising tool for the detection of involuntary gluten exposure, it is important to consider that short-term transgressions may not necessarily reflect a patient’s habits. Therefore, the GIP measurement in stool may not replace, but complement dietitian assessment in the monitoring of GFD compliance. Increased accuracy in this process may lead to greater compliance, improvement in clinical outcomes and prevention of complications. Finally, GIP may become an important research tool in the future, in particular for trials testing new pharmacological approaches for CD.
HIGHLIGHT - PUBLICATION IN BASIC RESEARCHCommentary on:
Intestinal cell damage and systemic immune activation in individuals reporting sensitivity to wheat in the absence of coeliac disease
Melanie Uhde, Mary Ajamian, Giacomo Caio, Roberto De Giorgio, Alyssa Indart, Peter H Green, Elizabeth C Verna, Umberto Volta, Armin Alaedini
A recently published paper in Gut may explain why certain individuals, who do not have celiac disease or wheat allergy, develop gastrointestinal and extra-intestinal symptoms after ingesting wheat. Of the gluten-related disorders, celiac disease is the most well studied and the genetics and adaptive immune responses involved in CD have been well characterized. However, some individuals develop non-specific symptoms that are triggered by wheat and related cereals, yet CD and wheat allergy have been ruled out. This clinical entity has been termed non-celiac gluten sensitivity or non-celiac wheat sensitivity (NCGS/NCWS). As this suggests, the exact trigger for symptoms is unknown, and researchers have little understanding as to why some individuals develop CD-like symptoms, yet lack the characteristic serological and genetic markers of CD. The lack of a known trigger and biomarkers make diagnosing and treating NCWS difficult. Moreover, the increased interest from the general public in gluten-related disorders highlights a need to better understand the physiological basis for symptoms. In the December issue of Gut, Uhde et al investigated whether patients with NCWS had systemic immune activation that correlated with a compromised epithelial barrier and symptom generation.
Researchers studied a group of patients with NCWS, in whom CD and wheat allergy had been ruled out and whose symptoms disappeared while on a gluten-free diet, a group of patients with biopsy confirmed CD, and a group of healthy controls. Serum samples were available from all patients and controls while on a gluten-containing diet, and from a subset of NCWS patients following 6-months of a gluten-free diet.
Unlike CD patients, those with NCWS did not have elevated anti-Tg2 antibodies or antibodies against deamidated gliadin while consuming a gluten-containing diet. On the other hand, NCWS patients had elevated IgA, IgG and IgM antibodies to native gliadin compared to healthy controls, and similar IgG levels to those found in CD patients. The antibody response to gliadin in NCWS patients was not associated with the presence of the CD HLA-DQ2/8 genotypes. Interestingly, patients with NCWS, but not CD or healthy controls, showed increased systemic immune activation, as evidenced by increased presence of serum LPS binding protein (LBP) and soluble CD14. The NCWS cohort also had increased antibody reactivity (IgG and IgM) to LPS and bacterial flagellin, whereas the CD cohort had increased IgA reactivity to LPS. These markers are indicative of increased microbial translocation into circulation in the NCWS patients. Elevated LBP and soluble CD14 in the NCWS group correlated with increased epithelial cell damage, as measured by serum FABP2. Following 6-months of a diet, that excluded wheat and related cereals, in a subset of the NCWS cohort, there was significant reduction in reported symptoms and anti-gliadin antibodies, as well as serum levels of LBP, soluble CD14, antibody reactivity to LPS and flagellin, and FABP2. This suggest there was a reduction in systemic immune activation, microbial translocation and epithelial damage following a gluten-free diet in NCWS patients. Finally, a multivariant analysis of the entire dataset showed that the three cohorts of patients, NCWS, CD, and healthy controls, clustered separately.
These findings reveal that sensitivity to wheat or gluten, in the absence of CD or wheat allergy, is associated with increased systemic immune activation and a compromised epithelial barrier that correlated with systemic translocation of microbial products, all of which normalize after elimination of wheat and related cereals from the diet. These exciting and novel results reveal physiological alterations in the intestinal barrier that may explain the generation in symptoms in a subset of individuals with NCWS and that these markers may be used to identify patients, monitor disease activity and their response to treatment. While the trigger underlying the physiological alterations and immune activation in these patients remains unknown, these findings provide an important framework in which to further investigate mechanisms. The large number of individuals who suffer from NCWS highlights the ongoing need for mechanistic studies.