ESPE Abstracts (2019) 92 P1-49

Gut Microbiome of North-American Children with and without Prader-Willi Syndrome (PWS)

Shima Afhami1, Hein Tun2, Ye Peng2, Suisha Liang2, Edward Deehan1, Karen Madsen1, Marie Gantz3, Lucila Triador1, Jens Walter1, Andrea Haqq1

1University of Alberta, Edmonton, Canada. 2University of Hong Kong, Hong Kong, China. 3RTI International, Research Triangle Park, USA

Introduction: Prader-Willi Syndrome (PWS), a common syndromic form of childhood obesity, is characterized by failure-to-thrive during infancy followed by progressive hyperphagia and obesity in childhood. The pathogenesis of hyperphagia and weight-gain in PWS is poorly understood and management strategies have had variable and limited success. Several studies support an etiological contribution of dysbiotic gut microbiota in the metabolic derangements of obesity; however, the specific role of the gut microbiome in PWS is not fully understood. This study aims to characterize the gut bacterial and fungal composition of children with and without PWS.

Methods: A stool sample, 3-day dietary record, hyperphagia questionnaire, and anthropometric measures (height, weight, waist-circumference) were collected. Composition of the bacterial and fungal community in stool samples was assessed by 16S rRNA and ITS gene amplicon sequencing, respectively. Operational taxonomic units (OTUs, clustered at 97% identity using Mothur [v.1.39.5]), differences in α- and β-diversity indices (α: Shannon, Simpson, Chao1; β: Jaccard, Bray-Curtis) and differential abundance testing (DESeq2, R-package) were assessed between PWS and control groups. Relationship of PWS-status (with or without PWS) and weight status (normal-weight vs. overweight) to OTU-level profiles (bacterial&fungal) were investigated using canonical correspondence analysis.

Preliminary Results: Fifty children aged 3-17 were recruited [nPWS=25 (14F:11M; median-age=6.3y; median BMI-z-score=0.83); ncontrol=25 (9F:16M; median-age=8.8y; median BMI-z-score=0.73). There was greater bacterial richness in the PWS-group compared to the controls (Choa1; P=0.02). No differences in other diversity indices were noted for the bacterial profile. ß-diversity (Bray-Curtis) was significantly different for the fungal profile among PWS and control groups (Adonis function; P<0.001). Differential abundance testing identified five bacterial and one fungal OTU that were differentially abundant between PWS and control groups. Bacterial OTUs related to Propionibacterium acnes (P=0.007), Staphylococcus (P<0.001), unclassified members of Enterobacteriaceae (P=0.001), and Lachnospiraceae (P=0.009), and a fungal OTU classified as Candida albicans (P=0.03) were overrepresented in PWS compared to the controls. The PWS group was also characterized by lower relative abundance of an OTU related to Akkermansia muciniphila (P<0.006). The relative abundance of the genus Prevotella was significantly higher in the PWS group compared to normal weight children without PWS (P=0.01).

Conclusion: Differences were observed in α-& β-diversity indices between groups. Higher differential abundance of taxa associated with inflammation and obesity and lower differential abundance of taxa linked with improved metabolic outcomes were observed in PWS compared to controls. Characterization of microbiota functional differences between groups is currently ongoing.

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