Effects of a low FODMAP diet on gut microbiota in individuals with treated coeliac disease having persistent gastrointestinal symptoms - a randomised controlled trial.

Individuals with coeliac disease (CeD) often experience gastrointestinal symptoms despite adherence to a gluten-free diet (GFD). While we recently showed that a diet low in fermentable oligo-, di-, monosaccharides and polyols (FODMAP) successfully provided symptom relief in GFD-treated CeD patients, there have been concerns that the low FODMAP diet (LFD) could adversely affect the gut microbiota. Our main objective was therefore to investigate whether the LFD affects the faecal microbiota and related variables of gut health. In a randomised controlled trial GFD-treated CeD adults, having persistent gastrointestinal symptoms, were randomised to either consume a combined LFD and GFD (n 39) for 4 weeks or continue with GFD (controls, n 36). Compared with the control group, the LFD group displayed greater changes in the overall faecal microbiota profile (16S rRNA gene sequencing) from baseline to follow-up (within-subject ß-diversity, P < 0·001), characterised by lower and higher follow-up abundances (%) of genus Anaerostipes (Pgroup < 0·001) and class Erysipelotrichia (Pgroup = 0·02), respectively. Compared with the control group, the LFD led to lower follow-up concentrations of faecal propionic and valeric acid (GC-FID) in participants with high concentrations at baseline (Pinteraction ≤ 0·009). No differences were found in faecal bacterial α-diversity (Pgroup ≥ 0·20) or in faecal neutrophil gelatinase-associated lipocalin (ELISA), a biomarker of gut integrity and inflammation (Pgroup = 0·74), between the groups at follow-up. The modest effects of the LFD on the gut microbiota and related variables in the CeD patients of the present study are encouraging given the beneficial effects of the LFD strategy to treat functional GI symptoms (Registered at clinicaltrials.gov as NCT03678935).

Nutritional assessment of women with celiac disease compared to the general population.

BACKGROUND & AIMS: The nutritional quality of a gluten-free diet is debated because of the elimination of grains that are important sources of nutrients. The aim of this cross-sectional study was to perform a nutritional assessment in treated women with celiac disease and ongoing symptoms, and compare dietary intake with a healthy reference group (Norkost 3). METHODS: Celiac disease patients with biopsy confirmed mucosal healing, but persistent gastrointestinal symptoms, were included from an ongoing clinical trial. Nutritional assessment included anthropometrics, blood samples and dietary intake obtained by two 24 h recalls. Dietary intake in celiac women was compared with dietary intake in healthy women (Norkost 3). Two sample t-test was used for comparison of CeD and Norkost 3 women. Adjustment for age, BMI, education and smoking, by use of multiple linear regression analysis, did not change the results. RESULTS: In total, 59 women with celiac disease and 925 women that participated in Norkost 3 were included, with a mean age of 45 years in both groups. Women with celiac disease had a higher proportion of energy (E%) from fat (39 vs 34%, P < 0.001) and saturated fat (15 vs 13%, P = 0.01), a lower E% from protein (16 vs 18%, P = 0.01) and a lower intake of dietary fiber (19 vs 22 g, P = 0.002) compared to Norkost 3 women. Women with celiac disease had a lower intake of bread, fruit and milk, and a higher intake of cereals and cheese compared to Norkost 3 women. The average requirement was not met for several micronutrients, but blood analysis revealed few nutritional deficiencies: two women with insufficient vitamin D status and one with insufficient folic acid status. CONCLUSION: The women with celiac disease had an unbalanced diet with a higher intake of total- and saturated fatty acids and a lower intake of fiber compared to the general population. These findings emphasizes the need for nutritional follow-up of celiac patients and development of nutrient dense gluten-free products.

A Low FODMAP Diet Reduces Symptoms in Treated Celiac Patients With Ongoing Symptoms-A Randomized Controlled Trial.

BACKGROUND & AIMS: A gluten-free diet usually leads to mucosal remission in celiac disease, but persistent symptoms are common. A low fermentable oligo-, di-, monosaccharides and polyols (FODMAP) diet is an established treatment for irritable bowel syndrome (IBS). We have assessed the efficacy of a moderately low FODMAP diet on persistent symptoms in treated celiac patients. METHODS: A randomized controlled trial was performed from 2018 to 2019 in 70 adults with biopsy-proven celiac disease. Inclusion criteria were as follows: persistent gastrointestinal symptoms defined by a Gastrointestinal Symptom Rating Scale (GSRS)-IBS version score of 30 or higher, gluten-free diet adherence for 12 months or longer, and serologic and mucosal remission. Participants were randomized to a low FODMAP-gluten-free diet (intervention) or usual gluten-free diet (control). The GSRS-IBS score was recorded at baseline and at weeks 1 to 4, and the Celiac Symptom Index at baseline and at week 4. Statistics included marginal models for repeated data and analyses of covariance. RESULTS: We included 34 participants in the intervention group and 36 in the control group. Time development of GSRS-IBS total scores differed significantly between the groups (Pinteraction < .001), evident after 1 week (mean difference in intervention vs control, -8.2; 95% CI, -11.5 to -5.0) and persisting through week 4 (mean difference in intervention vs control, -10.8; 95% CI, -14.8 to -6.8). Moreover, significantly lower scores were found for the dimensions of pain, bloating, diarrhea, and satiety (Pinteraction ≤ .04), but not constipation (Pinteraction = .43). FODMAP intake during the intervention was moderately low (mean, 8.1 g/d; 95% CI, 6.7-9.3 g/d). The Celiac Symptom Index was significantly lower in the intervention group at week 4 (mean difference, -5.8; 95% CI, -9.6 to -2.0). CONCLUSIONS: A short-term moderately low FODMAP diet significantly reduced gastrointestinal symptoms and increased celiac disease-specific health, and should be considered for the management of persistent symptoms in celiac disease. CLINICALTRIALS: gov: NCT03678935.

Detection of gluten immunogenic peptides and the Celiac Disease Adherence Test to monitor gluten-free diet: a pilot study.

Gluten immunogenic peptides (GIP) in feces and/or urine have recently been proposed as a sensitive and specific marker to detect ongoing gluten intake. Here, we compared GIP with the Celiac Disease Adherence Test (CDAT), a simple validated self-administered questionnaire that measures adherence to gluten-free diet (GFD). Of 70 subjects (59 women), six were classified as non-adherent by fecal GIP (mean 0.23 µg/g, standard deviation 0.08, range 0.082-0.319), including five classified as non-adherent by CDAT. GFD adherence was significantly higher by GIP than CDAT (p < 0.001). Fecal GIP may be useful as a biomarker for ongoing gluten intake that is not possible to detect with current clinical methods to assess GFD adherence, and may play a role in the management of persistent gastrointestinal symptoms in celiac disease.

High disease burden in treated celiac patients - a web-based survey.

BACKGROUND: Strict adherence to a gluten-free diet usually leads to clinical and histological remission in celiac disease. Few studies have investigated the prevalence of persistent symptoms in a celiac population. We aimed to study the impact of gastrointestinal symptoms on general health in a large number of treated celiac patients, and describe the prevalence of persistent gastrointestinal symptoms and investigate associated factors. METHODS: Adults with celiac disease filled out background questions, the Celiac Symptom Index (CSI) and the celiac disease adherence test (CDAT) in a web-based national survey. Participants who reported gastrointestinal symptoms during the previous week also recorded the gastrointestinal symptom rating scale-irritable bowel syndrome version (GSRS-IBS). Statistical analysis included chi-squared test, t-test, correlation, and linear regression. RESULTS: Of 3834 participants (82% women; mean age 47 years), 54% reported gastrointestinal symptoms the previous week, and 30% of these had CSI score ≥45, indicative of the relatively poor quality of life (vs. 5% among those without gastrointestinal symptoms). The prevalence of persistent gastrointestinal symptoms (GSRS-IBS ≥30) was 40% and the most prominent symptoms were bloating (44%) and pain (37%). Age, sex, symptoms at the time of diagnosis, comorbidity, dietary adherence and CeD-specific health were significantly associated with gastrointestinal symptoms (p < .001). CONCLUSION: In this national cross-sectional study among participants with celiac disease, persistent gastrointestinal symptoms were frequent, and were associated with a high symptom burden and reduced CeD-specific health. Several factors were associated with gastrointestinal symptoms, but more research is needed to find the cause of persistent symptoms in patients with celiac disease.