Gluten-free diets in coeliac disease: novel insights into gut function and the microbiome

17th February 2025

The reasons for alterations in the gut microbiome and gastrointestinal function in coeliac disease and how gluten-free dietary restrictions may further impact the gut are not well understood. Here, Carolyn Costigan, Frederick Warren and Luca Marciani, co-investigators of a recent study assessing gut function and the metagenome in coeliac disease, discuss how the results could provide a first step towards finding new targeted ways of treating the condition.

Coeliac disease is an autoimmune condition in which ingesting gluten – a protein found in wheat, rye and barley – triggers an immune response that damages the small intestine. The only current treatment for coeliac disease is adherence to a lifelong gluten-free diet, which aims to heal the intestinal mucosa, reverse enteropathy and relieve symptoms.

Despite avoiding gluten altogether, many people with coeliac disease have ongoing gastrointestinal problems, suggesting that the diet might not fully restore gut function or the microbiome.

Our observational cohort study (MARCO – MAgnetic Resonance Imaging in COeliac disease) sought to explore the effects of coeliac disease and a gluten-free diet on gut function and the microbiome.

Using novel magnetic resonance imaging (MRI) methods, we investigated small bowel water content and whole gut transit time. Using state-of-the-art shotgun metagenomics techniques, microbiome composition was investigated before and after one year of following a gluten-free diet.

The study recruited 36 newly diagnosed individuals with coeliac disease and 36 healthy volunteers as controls. Patients were matched for age, sex and body mass index. All underwent MRI scans to assess gut function and provided stool samples for microbiome analysis.

How was gut function impacted?

The patients with coeliac disease were studied at diagnosis and again after 12 months of following a strict gluten-free diet. The controls did not alter their diet.

• Small bowel water content

People with coeliac disease had higher small bowel water content at the start of the study, suggesting impaired absorption and motility in the gut. While this increased water content improved slightly after one year of the diet, it did not return to normal levels.

• Whole gut transit time

Initially, transit time for food through the gut was longer in people with coeliac disease compared with healthy controls. Transit times improved after a year of being gluten-free but remained slower than in the control group.

• Gut symptoms and wellbeing

Gastrointestinal symptoms such as bloating and abdominal pain, as well as overall wellbeing, in people with coeliac disease improved after a year of avoiding gluten, but they did not return to the levels seen in healthy individuals.

Gluten-free diets and the gut microbiome

Before starting the gluten-free diet, the patients’ microbiomes differed distinctly from those of the healthy control group. For example, patients had higher levels of Escherichia coli (E. coli) and Enterobacter and lower levels of certain beneficial bacteria. These differences may be linked to the inflammation and malabsorption in coeliac disease.

After one year on the gluten-free diet, there were significant shifts in the microbiome of the patients, although they still did not revert to the microbiome seen in healthy controls. Notably:

• Levels of Bifidobacterium – a genus of bacteria beneficial for gut health – decreased. This reduction suggests that the gluten-free diet may limit beneficial bacterial species that help digest fibre
• New bacterial species, such as Blautia wexlerae, increased in abundance
• There was also a change in the microbiome’s ability to process certain types of fibre, particularly arabinoxylan and resistant starch, which are abundant in wheat. This may explain the reduced levels of beneficial fibre-digesting bacteria after starting the gluten-free diet
• There were also alterations in microbial pathways related to protein and carbohydrate metabolism, which could reflect malabsorption issues in patients with coeliac disease.
• The changes in microbiome composition correlated with improvements in some gastrointestinal symptoms and gut function but not to the level of the healthy controls.

Our study also found that gut transit time and colonic volume were linked to microbiome composition. For instance, slower gut transit was associated with certain bacteria such as Akkermansia muciniphila.

Faster transit correlated with different bacterial species including Faecalibacterium prausnitzii, Gemmiger formicilis and several Agathobacter species.

These associations highlight the complex relationship between gut function and microbial communities.

Limitations, implications and future directions

Limitations included a relatively short follow-up period of one year, which might not be long enough to see a full recovery of the intestinal lining. Histological recovery of the gut mucosa was not assessed, as only serological tests were used to confirm adherence to the diet. The stool microbiome analysis may also not fully reflect changes in the small intestine, which could be more directly impacted by gluten-related inflammation.

Nevertheless, the findings suggest that while the gluten-free diet alleviates some symptoms and improves gut function, it does not completely restore gut health or the microbiome in people with coeliac disease.

The reduction in beneficial gut bacteria, such as Bifidobacterium, and the increase in bacteria associated with inflammation, such as E. coli, indicate that the diet might have unintended negative effects on gut health. This opens the door for potential future therapies, such as targeted prebiotics or probiotics, that could help restore the gut microbiome and improve overall health in coeliac disease.

The findings point to the need for further research on cutting-edge interventions to complement the diet and further improve gut health and quality of life in people with coeliac disease.

Take-home messages: gluten-free diets and coeliac disease

1. Coeliac disease patients had higher small bowel water content and delayed whole gut transit time compared with healthy volunteers
2. One year of a gluten-free diet improved symptoms and wellbeing but did not fully normalise gut function or microbiome composition
3. Restricting gluten significantly reduced Bifidobacteria and increased Blautia wexlerae in the gut microbiome
4. Changes in microbiome composition were associated with gut transit time and colonic volume
5. Observing a gluten-free diet led to significant alterations in carbohydrate-degrading enzyme profiles, specifically those involved in starch and arabinoxylan breakdown
6. In future, targeted prebiotic or probiotic therapies may be suitable to help restore the gut microbiome and improve overall health in coeliac disease.

Authors

Carolyn Costigan PhD
Nottingham Digestive Diseases Centre, Translational Medical Sciences, School of Medicine, University of Nottingham; NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust, UK

Frederick Warren PhD
Quadram Institute Bioscience, Norwich Research Park, Norwich, UK

Luca Marciani PhD
Nottingham Digestive Diseases Centre, Translational Medical Sciences, School of Medicine, University of Nottingham; NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust, UK

Early introduction of gluten reduces incidence of coeliac disease

1st October 2020

The enquiring about tolerance (EAT) study is an open-label randomised trial of a dietary intervention for the prevention of food allergy (including coeliac disease) in which potentially allergenic foods were introduced to an infant’s diet at an early age.

In the present study, a team from the Paediatric Allergy Research group, Kings College, London, focused on the development of coeliac disease at 3 years of age, after the introduction of gluten, a protein present in wheat that triggers the disease, from 4 months of age. A total of 1004 infants from the general population of England and Wales, were enrolled in the study and were all breast-fed until 13 weeks of age, after which they were randomised to consume six allergenic foods; cow’s milk, hen’s egg, peanut, sesame, cod fish and wheat in addition to breast milk (intervention group) or to continue with exclusively with breast milk until 6 months of age (control group), as recommended by UK government guidelines. The weekly recommended dose of wheat for a child was set at 4g of wheat protein and this was provided as wheat-based cereal biscuits (Weetabix) or equivalent. The team calculated that this was equivalent to a gluten dose of 3.2g/week and though this was set as the minimum intake, no maximum limits were set. The families were asked to complete weekly questionnaires through to 1 year and then every 3 months until 3 years of age.

Findings
For the 1004 (488 given the allergenic foods) infants included in the final analysis, 514 were male (51.2%) and the mean gluten intake between ages 4 and 6 months was 0.49g/week for the control group compared to 2.66g/week for the intervention group. At 8 months of age, gluten consumption had increased to 8.21g/week in the intervention group. Interesting by 3 years of age, 7 children in the control group but none of those in the gluten group, at developed coeliac disease.

Given the relatively small sample size, the authors called for more studies to confirm whether early introduction of gluten is an effective strategy to prevent the development of coeliac disease.

Reference
Logan K et al. Early gluten introduction and celiac disease in the EAT study. A prespecified analysis of the EAT randomised clinical trial. JAMA Pediatr doi:10.1001/jamapediatrics.2020.2893