The influence of a short-term gluten-free diet on the human gut microbiome

Abstract

Background: A gluten-free diet (GFD) is the most commonly adopted special diet worldwide. It is an effective treatment for coeliac disease and is also often followed by individuals to alleviate gastrointestinal complaints. It is known there is an important link between diet and the gut microbiome, but it is largely unknown how a switch to a GFD affects the human gut microbiome.

Methods: We studied changes in the gut microbiomes of 21 healthy volunteers who followed a GFD for four weeks. We collected nine stool samples from each participant: one at baseline, four during the GFD period, and four when they returned to their habitual diet (HD), making a total of 189 samples. We determined microbiome profiles using 16S rRNA sequencing and then processed the samples for taxonomic and imputed functional composition. Additionally, in all 189 samples, six gut health-related biomarkers were measured.

Results: Inter-individual variation in the gut microbiota remained stable during this short-term GFD intervention. A number of taxon-specific differences were seen during the GFD: the most striking shift was seen for the family Veillonellaceae (class Clostridia), which was significantly reduced during the intervention (p = 2.81 × 10(-05)). Seven other taxa also showed significant changes; the majority of them are known to play a role in starch metabolism. We saw stronger differences in pathway activities: 21 predicted pathway activity scores showed significant association to the change in diet. We observed strong relations between the predicted activity of pathways and biomarker measurements.

Conclusions: A GFD changes the gut microbiome composition and alters the activity of microbial pathways.

Keywords: Biomarker; Gluten-free diet; Microbiome; Observation study.

Figures

Fig. 1

Timeline of GFD study, including number of participants and collected samples

Fig. 2

PCoA plot showing the differences in the samples. a Samples plotted on PCoA 1 and 2, percentage of explained variation is given in the legends. Each color represents an individual, the larger and less opaque spheres are gluten-free diet time points, and the smaller spheres in the same color are habitual diet time points. b The differences in the first component over the time points. There are two groups based on richness, i.e. high versus low, one individual had samples in both groups. The sample belonging to both richness groups has a bolder color

Fig. 3

a Cladogram showing the differentially abundant taxa. This plot shows the different levels of taxonomy. Gray indicates bacteria higher in the habitual diet and red indicates those higher in the gluten-free diet. The different circles represent the different taxonomic levels. (From inside to outside: Kingdom, Phylum, Class, Order, Family, Genus, and Species). b Comparison of the abundance of Veillonellaceae* in the gluten-free diet vs. habitual diet. In the plot, the aggregate “overall weeks” including correction is shown. * Veillonellaceae is placed in the order Clostridiales in GreenGenes 13.5. However, according to the NCBI classification, it belongs to order Negativicutes

Fig. 4

Box plot of predicted activity of butyrate metabolism per diet period (a) and the butyrate levels (mol/g) per diet period (b). There was a significant increase in activity in butyrate metabolism (q = 0.001877), but no change in butyrate level was observed