- 107 views
- 159 downloads
Profiling the Bacterial and Fungal Gut Microbiome of Children with and without Prader-Willi Syndrome (PWS)
-
- Author / Creator
- Afhami, Shima
-
Obesity is a complex multifactorial disease that has a large array of direct (e.g. altered metabolic and inflammatory profile) and indirect (e.g. mental health concerns etc.) consequences on health and is associated with increased morbidity and mortality. Prader-Willi Syndrome (PWS) is the most common syndromic form of childhood obesity, characterized by abnormally increased and insatiable appetite (hyperphagia). The pathogenesis of hyperphagia and weight gain in PWS is poorly understood and management strategies have been met with limited success.
The gut microbiome has been implicated in several metabolic disorders such as obesity and diabetes. Interest in the role of the gut microbiome in genetic forms of obesity has emerged, however the specific role of the gut microbiome in PWS and childhood obesity is not fully understood.
This thesis work features a cross-sectional case-control study with two major objectives. The first objective was to characterise and compare the gut microbiome composition in children with and without PWS. The second objective was to determine if collected metadata could help to explain the compositional differences between groups.
A total of fifty children (n=25 PWS and 25 Controls) aged 3-17 (male and female) were recruited for this study. For each participant, a stool sample, a 3-day dietary record, a hyperphagia questionnaire, and anthropometric measures were collected. For this work, both bacterial (16S rRNA via Illumina) and fungal (ITS2) sequences were considered. This is a novel result as the fungal component of the gut microbiome in PWS has not been previously explored.
The gut microbiome was compared both between PWS and control (CON) groups and between weight-classified subgroups (“overweight/obese” (OWOB) and “normal weight” (NW) subgroups). Assessments of alpha-diversity (Chao1, Shannon and Simpson indices), beta-diversity (Bray-Curtis) and differential abundance (DESeq2) were performed. Spearman correlations and canonical correspondence analysis (CCA) were used to assess associations between the microbial community (bacterial and fungal) and collected hyperphagia and dietary intake information.
Significant differences in fungal community structure (beta-diversity) were observed between the PWS and CON groups. These differences were observed when comparing PWS and CON individuals (PPWS vs CON < 0.001), as well as when comparing the PWS and CON groups in both the NW and in the OWOB weigh-class subgroupings (PNW PWS vs CON = 0.02 and P OWOB PWS vs CON < 0.001 respectively). Comparing within the PWS and CON groups for differences in NW and OWOB individuals did not yield any significant differences in beta-diversity. Unlike the fungal community, no differences were observed in the bacterial community structure between groups.
Higher bacterial Shannon diversity was observed in the CON group compared to the PWS group (p=0.04). For the fungal alpha-diversity assessment, the OWOB PWS group was found to have increased Chao1 richness compared to the OWOB CON group (p=0.04). No other significant differences were observed in alpha-diversity metrics.
The PWS group was found to be characterized by an increased relative abundance of the genus Candida and relative decreased abundance of Saccharomyces relative to that of the CON group. No differentially abundant taxa were found in the bacterial profile of the PWS and CON groups (2 group analysis), however differences were observed in pairwise analyses.
Group type (PWS vs CON) was found to have the greatest potential to explain variation in fungal communities in the CCA model. No statistically significant findings were observed between taxa and the hyperphagia and dietary intake data using correlations, however dietary components were a significant contributor to variation explained by the CCA model of fungal communities.
The results of this thesis work provide a rationale for future exploration of the fungal component of the gut microbiome in PWS to further elucidate the clinical implications of these findings. Additionally, an understanding of the unique gut microbial profile of children with PWS has the potential to unveil more personalized approaches for effective treatment of excessive weight gain and hyperphagia, ultimately leading to improvements in overall health and quality of life. -
- Graduation date
- Fall 2020
-
- Type of Item
- Thesis
-
- Degree
- Master of Science
-
- License
- Permission is hereby granted to the University of Alberta Libraries to reproduce single copies of this thesis and to lend or sell such copies for private, scholarly or scientific research purposes only. Where the thesis is converted to, or otherwise made available in digital form, the University of Alberta will advise potential users of the thesis of these terms. The author reserves all other publication and other rights in association with the copyright in the thesis and, except as herein before provided, neither the thesis nor any substantial portion thereof may be printed or otherwise reproduced in any material form whatsoever without the author's prior written permission.