Heavy Metal and Rice in Gluten-Free Diets: Are They a Risk?

A gluten-free diet (GFD) is the treatment of choice for gluten-related disorders. It has been associated with macro- and micronutrient deficiencies. Recently, consumption of arsenic-contaminated rice has raised concern because of the potential greater risk that it may represent for people on GFDs, whose rice consumption is high, since it is a fundamental cereal in GFDs. We reviewed the data published over the last 20 years in Medline and Scielo, in English, French and Spanish, on four metals (As, Hg, Cd, and Pb), to assess whether the evidence suggests that celiac disease or consumption of a GFD is associated with increased levels of blood/urinary metal concentrations. The review revealed a few articles that were directly related to the four metals and their relationships with a GFD. The evidence supports that rice-based products are a relevant source of As and other metals. Clinical studies and evaluations based on NHANES have indicated that persons on GFDs have higher As and Hg blood/urinary levels, suggesting that the diet and not the disease is responsible for it. The levels described are statistically significant compared to those of persons on complete diets, but far from toxic levels. The question of whether higher exposure to heavy metals associated with a GFD is biologically relevant remains unanswered and deserves study.

Mesenchymal stromal cells loaded with Paclitaxel (PacliMES) a potential new therapeutic approach on mesothelioma.

Malignant pleural mesothelioma is an asbestos-related tumor originating in mesothelial cells of the pleura that poorly responds to chemotherapeutic approaches. Adult mesenchymal stromal cells derived either from bone marrow or from adipose tissue may be considered a good model for cell-based therapy, a treatment which has experienced significant interest in recent years. The present study confirms that Paclitaxel is effective on mesothelioma cell proliferation in 2D and 3D in vitro cultures, and that 80,000 mesenchymal stromal cells loaded with Paclitaxel inhibit tumor growth at a higher extent than Paclitaxel alone. An in vivo approach to treat in situ mesothelioma xenografts using a minimal amount of 106 mesenchymal stromal cells loaded with Paclitaxel showed the same efficacy of a systemic administration of 10 mg/kg of Paclitaxel. These data strongly support drug delivery system by mesenchymal stromal cells as a useful approach against many solid tumors. We look with interest at the favourable opinion recently expressed by the Italian Drug Agency on the procedure for the preparation of mesenchymal stromal cells loaded with Paclitaxel in large-scale bioreactor systems and their storage until clinical use. This new Advanced Medicinal Therapy Product, already approved for a Phase I clinical trial on mesothelioma patients, could pave the way for mesenchymal stromal cells use as drug delivery system on other solid tumors for adjuvant therapy associated with surgery and radiotherapy.

Evaluation of a Single Determination of Gluten Immunogenic Peptides in Urine from Unaware Celiac Patients to Monitor Gluten-Free Diet Adherence.

INTRODUCTION AND AIM: Usually, adherence to the gluten-free diet (GFD) in celiac patients is indirectly assessed through serological analysis, questionnaires, or invasive methods such as intestinal biopsy. The detection of gluten immunogenic peptides in urine (urinary gluten immunogenic peptides-uGIP) is a novel technique that directly evaluates the ingestion of gluten. The aim of this study was to evaluate the clinical efficacy of uGIP in the follow-up of celiac disease (CD). METHODS: From April 2019 to February 2020, CD patients reporting complete adherence to the GFD were prospectively enrolled but were unaware of the reason for the tests. Urinary GIP, the celiac dietary adherence test (CDAT), symptomatic visual analog scales (VAS), and tissue transglutaminase antibodies (tTGA) titres were evaluated. Duodenal histology and capsule endoscopy (CE) were performed when indicated. RESULTS: A total of 280 patients were enrolled. Thirty-two (11.4%) had a positive uGIP test (uGIP+). uGIP+ patients did not show significant differences in demographic parameters, CDAT, or VAS scores. The tTGA+ titre was not related to the positivity of uGIP (14.4% vs. 10.9% in patients with tTGA+ and tTGA-). Regarding histology, 66.7% of the GIP+ patients had atrophy compared to 32.7% of the GIP patients (p-value 0.01). However, the presence of atrophy did not correlate with tTGA. Mucosal atrophy was detected in 29 (47.5%) out of 61 patients by CE. With this method, no noticeable dependence on uGIP results (24 GIP- vs. 5 GIP+) was observed. CONCLUSIONS: The single uGIP test was positive in 11% of CD cases referring a correct GFD adherence. Furthermore, uGIP results significantly correlated with the duodenal biopsy, formerly considered the gold standard for assessing CD activity.

Clinical features of type 1 and 2 refractory celiac disease: Results from a large cohort over a decade.

OBJECTIVES: Refractory celiac disease (RCeD) is a rare complication of celiac disease (CeD) with a severe prognosis. We describe a cohort of patients with RCeD, their clinical and histological features at diagnosis, after therapy and at lymphoma onset, and the rate and causes of death over a 17-year follow-up. METHODS: We retrospectively enrolled RCeD-I and RCeD-II patients attending our center between January 2002 and October 2019. Medical data were collected at diagnosis and during monitoring. Response to therapy, changes in RCeD molecular markers, number of hospitalizations, discharge diagnosis, and cause and date of death were evaluated. The control cohort consisted of 1015 responsive CeD patients. RESULTS: Compared with RCeD-I, RCeD-II more frequently exhibits diarrhea (83 vs 64%), anemia (61 vs 50%), hypoalbuminemia (70 vs 21%), parenteral nutrition need (48 vs 7%), ulcerative jejuno-ileitis (7 vs 39%), and extended small intestinal atrophy (62 vs 21%). One RCeD-I and six RCeD-II patients developed lymphoma. Ten RCeD-II patients died, four from lymphoma progression. Among RCeD-II patients, atrophy extension was the only parameter correlated with hypoalbuminemia and mortality. CONCLUSIONS: Clinical severity, response to therapy, and mortality differ between RCeD-I and RCeD-II. Atrophy extension, evaluated at capsule endoscopy, was associated with disease severity and mortality.

Diagnostic management of patients reporting symptoms after wheat ingestion.

Many patients report symptoms after wheat ingestion experiencing a wide spectrum of clinical manifestations. Three possible diagnoses have been recognized: celiac disease (CD), wheat allergy (WA), and non-celiac (gluten) wheat sensitivity (NCGS/NCWS). CD is a chronic immune-mediated disease of the small bowel caused by exposure to dietary gluten in genetically predisposed individuals, with a prevalence of approximately 1%. It is characterized by mucosal inflammation and atrophy following exposure to gluten and improvement after gluten withdrawal. Food allergies are immunological responses to a food antigen. WA is the expression of an immunologically mediated process that can be immunoglobulin E (IgE) or non-IgE mediated; its many symptoms include urticaria/angioedema, asthma, rhinitis, and anaphylaxis. NCGS/NCWS is characterized by gastrointestinal and/or extra-intestinal symptoms after ingestion of gluten-containing food in subjects not affected by CD or WA. The aim of this review is to help physicians and nutritionists diagnose the cause of symptoms reported after wheat ingestion, thus avoiding patient frustration, inappropriate testing, and incorrect or missed diagnoses. An algorithm for the diagnostic approach in these patients is provided, to help to diagnose CD, WA, NCGS/NCWS or to identify possible functional disorders as the wheat-sensitive irritable bowel syndrome. A personalized approach, regular follow-up, and the help of a skilled healthcare professional are mandatory for patients with symptoms following wheat ingestion is provided. A gluten-free-diet is often recommended for patients with self-reported gluten/wheat-dependent symptoms; for patients with symptoms similar to those of functional diseases while there is evidence that a low-FODMAP diet could be the first option.

Vaccination Status and Attitudes towards Vaccines in a Cohort of Patients with Celiac Disease.

(1) Background: The identification of vaccination status and attitudes towards vaccines among celiac disease (CD) patients is of great importance, but it has not yet been investigated. The aim of this study was to investigate coverage against vaccine-preventable diseases (VPDs), attitudes towards vaccinations, and its determinants among CD patients. (2) Methods: An anonymous web-based validated questionnaire was sent to a mailing list of CD adult patients. Patients were asked to self-report their previous vaccinations and attitudes towards vaccinations, which were defined as positive, negative, and partially positive/negative. The influencing factors towards vaccinations were investigated, and crude and adjusted odds ratios (AdjORs) with 95% confidence intervals (CIs) were calculated. (3) Results: The questionnaire was sent to 412 patients, with a response rate of 31.6% (130 patients, 105 women, median age 40 years, interquartile range 36-51). Patients self-reported vaccination against the following diseases: 73.8% tetanus, 42.3% flu, 20% measles, mumps and rubella, 19.2% meningitis, and 16.2% pneumococcus. Thirty-two people (24.6%) did not remember all of their previous vaccinations. In total, 104 (80%) respondents had a positive attitude towards vaccines, 25 (19.2%) a partially positive/negative one, and 1 a negative one. The determinants significantly influencing the positive attitude were being a graduate (AdjORs 7.49) and a belief in the possible return of VPDs with declining vaccination coverage rates (AdjORs 7.42), while the use of complementary and alternative medicines (AdjORs 0.11) and past negative experience (AdjORs 0.16) were associated with a negative attitude. (4) Conclusions: Despite four out of five CD patients showing a strong positive attitude towards vaccinations, one out of five had a partially negative one. Only a minority (16-20%) reported being vaccinated against some VPDs potentially harmful to their CD because of hyposplenism, such as meningitis and pneumococcus. The low vaccination rate against some VPDs, in spite of the 80% of CD patients stating a positive attitude towards vaccination, may be explained in part by patients' vaccine hesitancy and in part by a possible role of physicians in under-prescribing vaccinations to these patients. These results may be a starting point for developing specific vaccination campaigns to increase vaccination rates against VPDs in CD patients.

Circulating microRNAs Suggest Networks Associated with Biological Functions in Aggressive Refractory Type 2 Celiac Disease.

Despite following a gluten-free diet, which is currently the only effective therapy for celiac disease, about 5% of patients can develop serious complications, which in the case of refractory type 2 could evolve towards intestinal lymphoma. In this study, we have identified a set of 15 microRNAs in serum discriminating between the two types of refractory disease. Upregulated miR-770-5p, miR-181b-2-3p, miR-1193, and miR-1226-3p could be useful for the better stratification of patients and the monitoring of disease development, while miR-490-3p was found to be dysregulated in patients with refractory type 1. Finally, by using bioinformatic tools applied to the analysis of the targets of dysregulated microRNAs, we have completed a more precise assessment of their functions. These mainly include the pathway of response to Transforming Growth Factor ß cell-cell signaling by Wnt; epigenetic regulation, especially novel networks associated with transcriptional and post-transcriptional alterations; and the well-known inflammatory profiles.

Nutrition in Patients with Inflammatory Bowel Diseases: A Narrative Review.

Inflammatory bowel diseases (IBD) affect the gastrointestinal tract: they include Crohn's disease (CD) and ulcerative colitis (UC). Each has a different phenotypic spectrum, characterized by gastrointestinal and extra-intestinal manifestations. People living with IBD are very interested in diet, but little is known about the impact of diet on these patients; no guidelines are available yet. In this review, we analyze the dietary patterns of patients with IBD and the approach to the choices of foods both in adults and pediatric patients. Very often, IBD patients report an intentional avoidance of gluten to manage the disease; furthermore, a proportion of IBD patients believe that dairy products worsen their symptoms and that avoidance may help the disease. They have a low compliance with the Mediterranean Diet, which is considered to have potential benefits but is little used in practice. In conclusion, the review underscores the pivotal role of nutritional counselling in IBD patients, and the importance of future clinical studies to evaluate the beneficial effects of dietary recommendations in the management of IBD.

Effectiveness of Capsule Endoscopy and Double-Balloon Enteroscopy in Suspected Complicated Celiac Disease.

BACKGROUND & AIMS: Complicated celiac disease (CCD) is a rare but severe condition with a poor prognosis. Guidelines recommend use of capsule endoscopy (CE) to explore the small bowel (SB), followed by a double-balloon enteroscopy (DBE) in selected cases with suspected CCD. Our study aimed to evaluate the diagnostic yield (DY) of CE and DBE in identifying and monitoring CCD. METHODS: Consecutive suspected CCD patients were enrolled prospectively to undergo CE and/or DBE in the presence of: persistent symptoms despite a correct gluten-free diet (GFD), increased anti-transglutaminase antibodies titer, lack of adherence to the GFD, and CCD monitoring. The DY of CE and DBE were calculated. The incidence of neoplastic complications and mortality were assessed. RESULTS: In total, 130 patients (97 women; age, 49 ± 16 y) underwent 151 CEs and 23 DBEs. The DY of CE was 46%. Patients older than age 50 years (at CE examination or at CD diagnosis) with a CD duration shorter than 5 years were at higher risk of positive CE (relative risk, 1.6 and 1.7 in case of enrollement or CD diagnosis after 50 years of age, and 1.5 in case of short CD duration; P < .05) than their counterparts. Up to 40% of SB lesions were unreachable by upper endoscopy. At the end of the diagnostic work-up, 25 patients with premalignant/malignant lesions were identified: 12 type 1 refractory CD (RCD-1), 7 type 2 RCD (RCD-2), and 6 enteropathy-associated T-cell lymphoma (EATL). Six patients died: 2 patients with RCD-2 and 4 patients with EATL. CONCLUSIONS: In case of suspected CCD, CE should be the first-line approach to detect complications and to identify patients deserving DBE. Older and symptomatic patients with suspected CCD deserve a careful evaluation of the SB, especially during the first years after diagnosis.

Anti-SARS-CoV-2 immunoglobulin profile in patients with celiac disease living in a high incidence area.

BACKGROUND AND AIM: How symptoms and antibodies related to SARS-CoV-2 infection develop in patients with celiac disease (CD) is unclear. We aimed to investigate the impact of SARS-CoV-2 infection in CD patients. METHODS: CD patients were interviewed about the development of COVID-19 symptoms, compliance with anti-virus measures and adherence to a gluten-free diet (GFD). The presence of anti-SARS-CoV-2 IgG and IgA (anti-RBD and N proteins) was compared to that in non-CD subjects. Expression of the duodenal ACE2 receptor was investigated. When available, data on duodenal histology, anti-tissue transglutaminase IgA (tTGA), comorbidities and GFD adherence were analyzed. RESULTS: Of 362 CD patients, 42 (12%) reported COVID-19 symptoms and 21% of these symptomatic patients presented anti-SARS-CoV-2 Ig. Overall, 18% of CD patients showed anti-SARS-CoV-2 Ig versus 25% of controls (p = 0.18). CD patients had significantly lower levels of anti-N IgA. tTGA, duodenal atrophy, GFD adherence or other comorbidities did not influence symptoms and/or antibodies. The ACE2 receptor was detected in the non-atrophic duodenal mucosa of patients; atrophy was associated with lower expression of the ACE2 receptor. CONCLUSION: CD patients have an anti-SARS-CoV-2 Ig profile similar to non-celiac controls, except for anti-N IgA. No risk factors were identified among CD parameters and GFD adherence.

Clinical Value of Tissue Transglutaminase Antibodies in Celiac Patients over a Long Term Follow-Up.

INTRODUCTION & AIM: Anti-tissue transglutaminase antibody (tTGA) titer is used during the follow-up of celiac patients to evaluate gluten-free diet (GFD) responsiveness. However, no clear data are available on this issue. The aim of this study was to evaluate tTGA significance during celiac disease (CD) monitoring. METHODS: From January 2017 to January 2020, consecutive CD patients on a GFD with persistent positive tTGA were enrolled. Antibody titres were evaluated on a yearly basis from CD diagnosis to the last follow-up. Urinary gluten detection tests, duodenal histology and capsule enteroscopy (CE) were performed. A tTGA-positive cohort was compared with a control group composed of 212 treated CD patients with negative tTGA. RESULTS: 65 patients (12% males, median age at enrollment and CD diagnosis, 37 (14-86) and 31 (1-76), respectively, median follow up 4 (1-26) years) presented with positive tTGA during follow-up. Overall, the tTGA titres were 3 (1-79) fold increased (ULN). Three different tTGA trends were recognized: (I) 36 (55%) patients with a progressive titres decrease; (II) 16 (25%) patients with a fluctuating behavior; (III) 13 (20%) patients with a steady state or increased titres. tTGA+ patients did not present with different clinical and demographic parameters. Duodenal atrophy was present in 10% vs. 36% of the tTGA positive vs. negative group (p < 0.005), respectively. Gluten detection results were positive in 3 (8%) cases, all in the III group. In tTGA+ patients, CE did not identify any CD-related complications. CONCLUSIONS: tTGA positivity during CD follow up did not present a relevant clinical significance without association with autoimmune comorbidities and mucosal damage.

COVID-19 Vaccine: A Survey of Hesitancy in Patients with Celiac Disease.

(1) Background: COVID-19 vaccination campaigns offer the best hope of controlling the pandemic. However, the fast production of COVID-19 vaccines has caused concern among the general public regarding their safety and efficacy. In particular, patients with chronic illnesses, such as celiac disease (CD), may be more fearful. Information on vaccine hesitancy plays a pivotal role in the development of an efficient vaccination campaign. In our study, we aimed to evaluate COVID-19 vaccine hesitancy among Italian CD patients. (2) Methods: an anonymous questionnaire was sent to CD patients followed at our tertiary referral center for CD in Milan, Italy. Patients were defined as willing, hesitant and refusing. We evaluated the reasons for hesitancy/refusal and the possible determinants, calculating crude and adjusted odds ratios [AdjORs] with 95% confidence intervals [CIs]. (3) Results: the questionnaire was sent to 346 patients with a response rate of 29.8%. Twenty-six (25.2%) of the 103 respondents were hesitant, with a total refusal rate of 4.8%. The main reason was fear of adverse events related to vaccination (68.2%). Among hesitant patients, 23% declared that their opinion was influenced by their CD. The determinants positively influencing willingness to be vaccinated against COVID-19 were adherence to a GFD, perception of good knowledge about COVID-19 and its vaccines, and a positive attitude to previous vaccines (AdjOR 12.71, 95% CI 1.82-88.58, AdjOR 6.50, 95% CI 1.44-29.22, AdjOR 0.70, 95% CI 0.11-4.34, respectively). (4) Conclusions: CD patients should be vaccinated against COVID-19 and a specific campaign to address the determinants of hesitancy should be developed.

Mediterranean Gluten-Free Diet: Is It a Fair Bet for the Treatment of Gluten-Related Disorders?

Gluten-free diet (GFD) is the current treatment of gluten-related disorders. It eliminates wheat, barley, and rye, while the exclusion of oats is still under debate. GFD is based on a combination of naturally gluten-free foods and gluten-free substitutes of cereal-based foods. Although effective as treatment of gluten-related disorders, today there is concern about how to improve GFD's nutritional quality, to make it not only gluten-free, but also healthy. The "Mediterranean diet" (MedD) refers to the dietary pattern and eating habits typical of populations living in the Mediterranean basin, which have been associated with low prevalence of several diet-related pathologies. Here we present a narrative review of the current knowledge about GFD and MedD, their characteristics and central food components. Based on the Mediterranean diet pyramid developed by the Italian pediatric society, we propose a combination between the MedD and the GFD, an attractive alternative to reach a gluten-free state that at the same time is healthy, with a clear benefit to those who practice it.

How to manage celiac disease and gluten-free diet during the COVID-19 era: proposals from a tertiary referral center in a high-incidence scenario.

The outbreak of COVID-19 and SARS-CoV-2 infection is spreading worldwide as the first coronavirus pandemic. The clinical picture is variable but flu-like symptoms are common with bilateral interstitial pneumonia being the most frightening presentation. No specific therapies nor vaccine have been developed to date and the only way to limit the virus diffusion is by modifying one's lifestyle limiting social life and following strict hygienic precautions. No data is available on the risk of COVID-19 and its outcomes in celiac disease (CeD). The restrictions applied to counter COVID-19 can impact on CeD treatment and gluten-free dieting, the only available therapy for CeD. With the present manuscript, we aim to support gastroenterologists and nutritionists in the management of CeD patients in the new pandemic scenario, being conscious that availability and local situations are extremely various.

Efficacy of a High-Iron Dietary Intervention in Women with Celiac Disease and Iron Deficiency without Anemia: A Clinical Trial.

BACKGROUND AND AIM: Iron deficiency without anemia (IDWA) is a common finding in celiac disease (CD) and can also persist in case of good compliance and clinical response to a strict gluten-free diet (GFD). This scenario usually presents in CD women of child-bearing age in whom the imbalance between menstrual iron loss and inadequate iron intake from their diet plays the major role. A recommended approach to this condition is yet to be established. This study aimed to compare, in this subset of patients, the efficacy of a dietary approach consisting of an iron-rich diet against the traditional pharmacological oral-replacement therapy. MATERIAL AND METHODS: Between February and December 2016, consecutive CD female patients of child-bearing age as referred to our outpatient center with evidence of IDWA (ferritin <15 ng/mL or 15-20 ng/L with transferrin saturation <15%) were enrolled. After the completion of a 7-day weighed food intake recording to assess the usual iron dietary intake, the patients were randomized in two arms to receive a 12-week iron-rich diet (iron intake >20 mg/die) versus oral iron supplementation with ferrous sulfate (FS) (105 mg/day). Blood tests and dietary assessments were repeated at the end of treatment. The degree of compliance and tolerability to the treatments were assessed every month by means of specific questionnaires and symptoms evaluation. RESULTS: A total of 22 women were enrolled and divided in the diet group (n = 10, age 37 ± 8 years) and in the FS group (n = 12, age 38 ± 10 years). The food intake records demonstrated an inadequate daily intake of iron in all the enrolled subjects. At the end of the treatments, ferritin levels were higher in the FS group (8.5 (5) versus 34 (30.8), p = 0.002). Compliance and tolerability were similar in both treatment groups (89% versus 87%, p = ns). CONCLUSIONS: These findings did not support any equivalent efficacy of an iron-rich diet compared to a FS supplementation in non-anemic iron-deficient women affected by CD. However, the diet appeared a well-tolerated approach, and adequate dietary instructions could effectively increase the daily iron consumption, suggesting a role in the long-term management of IDWA, especially in patients who do not tolerate pharmacological supplementation.

Safety of occasional ingestion of gluten in patients with celiac disease: a real-life study.

BACKGROUND: Gluten-free diet (GFD) decreases the quality of life of celiac disease (CD) patients, who frequently ask to occasionally ingest gluten-containing food. We evaluated CD patients reporting voluntary and occasional transgressions to their GFD. METHODS: From October 2017 to September 2018, the patients reporting occasional and voluntary gluten ingestion (GFD-noncompliant) were prospectively enrolled. These patients underwent clinical examination, blood tests, duodenal biopsy, capsule enteroscopy (CE), and a validated food-frequency questionnaire (FFQ) assessing the frequency and quantity of gluten intake. Mortality was calculated and compared to the general population. A group of patients on strict GFD (GFD-adherent) acted as controls. RESULTS: One thousand three hundred seventy-eight CD patients were evaluated during the study period. One hundred nine (8%) reported occasional (weekly or monthly) voluntary ingestion of gluten. The mean gluten intake was 185.2 ± 336.9 g/year, and the duration of their incorrect GFD was 8.6 ± 6.9 years. Among the noncompliant patients, 57% did not present any histological alteration; furthermore, the Marsh score profile was not different between compliant and noncompliant patients. Seventy percent did not present any alteration at CE. Seventy-five percent of patients reported no gastrointestinal symptoms after gluten ingestion. Twenty-three percent of patients in the GFD-noncompliant group presented positive tTG-IgA. No association was found between gluten intake, clinical symptoms, and biomarkers. Mortality was not different between the groups and the general population. CONCLUSIONS: Our results are that in a real-life scenario, a group of CD patients on long-term gluten intake showed no significant clinical symptoms or small bowel damage, thus suggesting that a degree of tolerance towards gluten consumption can be reached.

Dietary Gluten as a Conditioning Factor of the Gut Microbiota in Celiac Disease.

The gut microbiota plays a relevant role in determining an individual's health status, and the diet is a major factor in modulating the composition and function of gut microbiota. Gluten constitutes an essential dietary component in Western societies and is the environmental trigger of celiac disease. The presence/absence of gluten in the diet can change the diversity and proportions of the microbial communities constituting the gut microbiota. There is an intimate relation between gluten metabolism and celiac disease pathophysiology and gut microbiota; their interrelation defines intestinal health and homeostasis. Environmental factors modify the intestinal microbiota and, in turn, its changes modulate the mucosal and immune responses. Current evidence from studies of young and adult patients with celiac disease increasingly supports that dysbiosis (i.e., compositional and functional alterations of the gut microbiome) is present in celiac disease, but to what extent this is a cause or consequence of the disease and whether the different intestinal diseases (celiac disease, ulcerative colitis, Crohn disease) have specific change patterns is not yet clear. The use of bacterial-origin enzymes that help completion of gluten digestion is of interest because of the potential application as coadjuvant in the current treatment of celiac disease. In this narrative review, we address the current knowledge on the complex interaction between gluten digestion and metabolism, celiac disease, and the intestinal microbiota.

Impact of FODMAP Content Restrictions on the Quality of Diet for Patients with Celiac Disease on a Gluten-Free Diet.

Restrictive diets as gluten-free (GFD) or reduced in Fermentable, Oligosaccharides, Disaccharides, Monosaccharides, and Polyols (FODMAP) are used to improve gastrointestinal (GI) symptoms in sensitive individuals. Aiming at comparing the nutritional quality and effects of a regular GFD regimen (R-GFD) and a low-FODMAP GFD (LF-GFD), in 46 celiac patients with persistent GI symptoms we conducted a randomized, double-blind intervention-controlled study. Patients received a personalized diet, either a strict GFD (n = 21) or a LF-GFD (n = 25) for 21 days. A validated food-frequency questionnaire before intervention and a 7-day weighed-food record after the intervention assessed the diets. Patients were 41.1 ± 10.1 years (mean ± SD), 94% women, with mean BMI 21.8 ± 2.9 kg/m2. On day 21, patients on R-GFD still showed poor nutritional adequacy compared to dietary recommendations, with decreased energy intake, even though an improvement in carbohydrates and folates was observed (all p < 0.025). In both groups, intake of iron, calcium, vitamin D, sodium and folates did not meet daily recommendations. As expected, consumption of legumes and grains was lower and that of fruits was higher in the LF-GFD group than in the R-GFD one (all p < 0.05). The nutritional quality of both diets was not different. When restrictive diets are useful to improve the persistent GI symptoms, careful nutritional surveillance and counseling is mandatory.