Sleep-Wake Cycles of Individuals with Inflammatory Bowel Disease

Abstract

Background: Individuals with inflammatory bowel disease (IBD), a chronic illness of the gastrointestinal (GI) system, report high rates of poor sleep quality and sleep disturbances. Among those with IBD, sleep problems are more prevalent during active disease, a period marked by inflammation and severe GI symptoms. Animal models have demonstrated that altered sleep-wake cycles and disruptions in the circadian rhythm can cause increased susceptibility to inflammation and intestinal dysbiosis. IBD studies report the association between increased GI symptoms and inflammation with less consistent daily rhythms. Limited studies have examined the social and societal factors that impact the sleep-wake cycles of those with IBD. The overall purpose of this dissertation is to explore different aspects of the sleep-wake cycles of individuals with IBD through the social-ecological model of sleep (SEM).Methods: In this prospective cohort study, 50 participants were recruited from an IBD clinic in Seattle, WA. Individuals collected wrist actigraphy for 10 days, a stool sample, baseline surveys, and daily electronic diaries. 24 of the 50 participants completed semi-structured interviews. The aim of manuscript one was to examine the relationship between sleep and fatigue outcomes (i.e., PROMIS sleep disturbance and fatigue, Pittsburgh Sleep Quality Index), GI symptoms (i.e., abdominal pain, bloating, diarrhea, constipation, nausea), and fecal calprotectin with rest-activity rhythm (RAR) characteristics and social jetlag (SJL). RAR characteristics and SJL were analyzed from wrist actigraphy. Fecal calprotectin, a biomarker of gut inflammation, was measured using ELISA assays from the stool samples. Survey data used were sleep and fatigue outcomes and GI symptoms from daily diaries. In manuscript two, generalized estimating equations (GEE) was used to test if sleep fragmentation from wrist actigraphy and self-reported sleep quality from daily diaries predicted next-day GI symptoms (i.e., abdominal pain, bloating, diarrhea, constipation, nausea). For manuscript three, a hybrid thematic analysis was used to explore factors across the individual, social, and societal levels that impact sleep-wake cycles of those with IBD, and describe the strategies used to improve sleep health. Results: There were no significant relationships between RAR characteristics and SJL with sleep, fatigue, GI symptoms, and fecal calprotectin. The midline estimating statistic of rhythm (MESOR) and relative amplitude were higher in those in remission than those with clinically active disease. Sleep fragmentation and self-reported sleep quality were non-statistically significant predictors of next-day GI symptoms. Among the participants, wake after sleep onset was higher, and sleep efficiency was lower than the recommendations from the National Sleep Foundation. The factors and strategies that impact sleep-wake cycles were three individual-level themes (7 subthemes) and three social-level themes (4 subthemes). The individual-level themes were lifestyle and behaviors (daytime behaviors and habits, nighttime influences, diet, and technology use), physical health (IBD and GI symptoms; non-GI pain, fatigue and other health conditions; medications and supplements), and mental health. The social-level themes were sleep environment, interpersonal relationships (partner, children, pets, friends) and work. Participants provided strategies that both directly and indirectly positively impacted sleep health. Conclusion: In this study, participants in clinical remission had more robust rest-activity rhythms than those in active disease. There is an opportunity for improvements in nighttime sleep (e.g., sleep efficiency, wake after sleep onset) despite the sample’s average total sleep time and sleep onset latency meeting recommendations by the National Sleep Foundation. Future multilevel sleep interventions in the IBD population should accommodate not only individual-level factors but also social-level factors that impact sleep-wake cycles. Although the social-level factors identified in the study might not be modifiable in the lives of those with IBD, it is important to account for these factors when creating tailored interventions. Future studies should examine different aspects of the circadian rhythm (e.g., chronotype, dim light melatonin onset) and the peripheral intestinal clock alongside individual-level IBD health outcomes, such as inflammation and GI symptoms, and social-level factors.