Gut Microbiome Composition and Metabolic Changes Are Correlated with Sleep Efficiency and Disease Phenotype in Pediatric Inflammatory Bowel Disease - Abstract
Background and aims: Sleep disturbances are common in patients with Inflammatory Bowel Disease (IBD), defined by alterations in the quality, timing, and amount of sleep. We hypothesized that disruption of the gut microbiota in pediatric IBD patients may induce sleep disturbances and worsen patient outcomes. Methods: Children < 17 years with IBD were assessed for sleep disturbances using a sleep diary. Clinical disease activity indices were calculated. Patient stool was collected for calprotectin measurement, and to examine microbiota (metagenomics; Kraken2-R), Short Chain Fatty Acid (SCFA; gas chromatography), and metabolite (metagenomics; Maaslin2) profiles. Regression analyses assessed association of Fecal Calprotectin (FCal), clinical activity indices, sleep
efficiency/length, and time in bed. Results: Fifteen of 80 (18.6%) children had clinically active disease; 23 (28.8%) had FCAL > 100 ug/g. 24 of 80 (30%) children had abnormal sleep efficiency < 90% and 22 (27.5%) had subnormal sleep duration. High FCAL was associated with altered sleep efficiency (P = 0.03). Disease phenotype (L3, B2) demonstrated numerous significant correlations with microbiota (e.g., Veillonella, Akkermansia, Allistipes) and metabolites (e.g., H-transport, NADH dehydrogenase, 6-phospphofruktokinase). Average length of sleep was associated with significant changes in microbiota diversity (e.g., Bacteroides, Enterococcus, Bifidobacterium, Alistipes, Streptococcus, Ruminococcus) and vast metabolic changes, primarily related to energy production. Finally, stool propionate negatively correlated with sleep efficiency and total time in bed (P < 0.05). Conclusions: Our findings suggest that gut microbiota diversity, abundance, and functions (metabolites) are associated with altered sleep patterns in pediatric IBD and more aggressive disease phenotypes. These data support the need to further investigate causal relationships between gut microbiota, sleep efficiency, and disease outcomes in children with IBD.