The gut microbiota characteristics of children with coeliac disease and the effect of treatment

Zafeiropoulou, Konstantina (2018) The gut microbiota characteristics of children with coeliac disease and the effect of treatment. MSc(R) thesis, University of Glasgow.

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Objectives and study:
The incidence of coeliac disease (CD) has been significantly increasing over the past decades in Western society [1]. The rapid increase in incidence, along with the relatively low prevalence of the disease among genetic susceptible individuals suggest a strong contribution of environmental factors in the development of CD, including changes in the gut microbiota. Recent literature indicates that the gut microbiota is altered in CD. However, the evidence is inconclusive and it still has to be confirmed whether a disturbed microbiota is contributing to disease development, or is merely a consequence of disease activity and treatment with gluten free diet (GFD). The current study evaluated microbiota compositional and functional characteristics in treated CD children (TCD), newly diagnosed untreated CD (UCD), their siblings and healthy controls (HC).

Faecal samples were collected from TCD on GFD for at least one year, UCD, their siblings and HC. UCD were followed prospectively for six and 12 months after the initiation of treatment with GFD. Dietary intake characteristics were evaluated using food frequency questionnaire (FFQ), short chain fatty acids (SCFA) were measured using gas chromatography (GC) and microbial community structure and composition using 16S sequencing. Compliance with GFD was evaluated based on the Biagi score, clinicians’ evaluation, serum tissue transglutaminase (tTG) immunoglobulin A (IgA) levels, as well as the novel biomarker faecal gluten immunogenic peptide (GIP).
145 participants had faecal samples collected (45 TCD, 20 UCD, 23 siblings of the CD children and 57 HC). Thirteen UCD patients provided paired samples at baseline, six and 12 months on GFD. TCD had significantly lower concentrations of propionic, butyric, valeric, and caproic acids per total faecal output than HC (all p< 0.05). Moreover, TCD microbiota clustered separately from HC (R2= 2.56, p= 0.013) in the non-metric multidimensional scaling (NMDS) plot for the Bray-Curtis dissimilarity index at genus level. There was no significant difference in the microbiota structure and functionality between UCD and HC children. In the prospective cohort, acetic acid significantly increased [(72.5 (1.4)) Vs (65.5 (1.3), p= 0.003)] and butyric acid significantly decreased [(9.7 (1.4)) Vs (13.6 (1.04), p= 0.013)] at six months on GFD. The relative abundance of OTU_908 Anaerostipes, a butyrate-producing bacterium, also decreased at six months on GFD. Furthermore, the relative abundance of acetic acid was significantly associated with GIP levels in faeces of CD children who were on GFD for at least one year. Increased GIP levels in faeces, so decreased compliance with GFD, were strongly associated with decreased levels of acetic (p< 0.05), indicating that changes in the microbiota metabolites concentration were significantly associated with the GFD adherence. Similarly, compared to baseline values, isobutyric and isovaleric acids significantly decreased at 12 months on GFD (p< 0.05).
Significant differences in the relative abundance of OTU_259 Erysipelatoclostridium and OTU_98 Ruminococcaceae were observed in faeces of CD children after treatment with GFD, although they were of different direction in the prospective and cross-sectional study. Compared to baseline values, the relative abundance of OTU_259 and OTU_98 significantly decreased at six months on GFD, whereas the relative abundance of both OTU were significantly higher in TCD than UCD children, in the cross-sectional study.
The findings of the present study indicate that alterations in microbiota composition and SCFA in patients with CD are most likely a secondary consequence of adherence to a GFD rather than a primary disease effect. Although no UCD microbiota “dysbiosis” was observed, faeces of UCD children had significantly lower relative abundance of 31 distinct OTU. This may be used to unravel our knowledge on the disease process, but these alterations observed in this study need replication in larger cohorts of CD children. Finally, the altered microbiota functionality of patients with CD after the initiation of GFD could be used to assess compliance with GFD, monitor disease improvement but also unravel the mechanisms through which GFD exhibits its beneficial effect.

Item Type: Thesis (MSc(R))
Qualification Level: Masters
Subjects: R Medicine > R Medicine (General)
R Medicine > RJ Pediatrics
Colleges/Schools: College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
Supervisor's Name: Gerasimidis, Dr. K. and Edwards, Prof. C. and Ijaz, Dr. U.
Date of Award: 2018
Embargo Date: 9 February 2022
Depositing User: Mrs Marie Cairney
Unique ID: glathesis:2018-8746
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 09 Feb 2018 15:40
Last Modified: 16 Feb 2020 17:02

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