Sleep disturbances and inflammatory bowel disease: a potential trigger for disease flare?

Abstract

Inflammatory bowel disease (IBD) is a waxing and waning disease characterized by diarrhea, abdominal pain and weight loss. Recently, there has been an increased interest in the roles that sleep, circadian rhythms and melatonin could have as regulators of inflammation in the Gl tract. Advances in our understanding of the molecular machinery of the circadian clock, and the discovery of clock genes in the GI tract are opening up new avenues of research for a role of sleep in IBD. Altering circadian rhythm significantly worsens the development of colitis in animal models, and preliminary human studies have shown that patients with IBD are at increased risk for altered sleep patterns. Further research is needed to clarify the role of disturbances in IBD.Keywords circadian rhythms; Crohn's disease; inflammatory bowel disease; melatonin; sleep; ulcerative colitis Ulcerative colitis (UC) and Crohn's disease (CD) are the two phenotypic patterns of inflammatory bowel disease (IBD) [1]. CD has a transmural pattern of inflammation that can occur anywhere in the GI tract (GIT) and is associated with the development of complications such as fistulas or strictures [2]. UC has a superficial inflammation that occurs only in the colon. This inflammation begins in the rectum and is usually limited to the left side of the colon but with time may extend over the entire colon [3]. Currently, over 2 million people in the USA are diagnosed with IBD and the last several decades have seen an increasing incidence of the disease [4]. IBD has a waxing and waning course with periods of asymptomatic remission interrupted with episodes of disease 'flare' where patients can present with bloody stools, diarrhea, fever and abdominal pain.Currently the etiology of IBD is not known and thus it is not surprising that there is no cure for IBD; the primary treatment goal is to improve patients' quality of life by treating flare ups and maintaining remission. The most effective approach to maintaining remission is to †

Systematic analysis of circadian genes using genome-wide cDNA microarrays in the inflammatory bowel disease transcriptome

“…In accordance with these findings and considering that the clock gene machinery controls cell proliferation in the gastrointestinal mucosa (Hoogerwerf et al, 2008) and gastrointestinal motility (Hoogerwerf, 2010), that alterations of circadian rhythmicity significantly worsen the development of colitis in animal models, and that altered sleep patterns in patients affected by CD and UC might influence disease severity or risk of flare-up (Swanson et al, 2011), therapeutic strategies could be implemented to circumvent circadian disruption and improve sleep quality in patients with IBD. Output genes, which are responsible for tissue specific metabolic or proliferative functions, link key tissue functions to the circadian environment, making these key functions available at specific times during each day when they are most needed.…”

Sleep Duration Affects Risk for Ulcerative Colitis: A Prospective Cohort Study

“…Considerable evidence supports an association between sleep and the immune system 31-35,373858 . Tang et al .…”

“…In particular, chronic sleep deprivation worsened histological and clinical severity of colitis. Sleep restriction also results in a reduction in circulating IL-2 and increases in TNF-α and monocyte chemoattractant protein-1, shifting the Th1/Th2 cytokine balance towards Th2 32375859 . Such shifts can favor the development of UC given the more dominant role of the Th2 pathway in its pathogenesis.…”

Circadian rhythms of gastrointestinal function are regulated by both central and peripheral oscillators

“…For example, ambulatory colonic pressure recordings from healthy individuals exhibit maximal colonic activity during the day, especially following awakening and following a meal, and minimal activity during the night. GI disease states also emerge when circadian clocks are disrupted (19,32,26). GI symptoms, such as abdominal pain, constipation, and diarrhea, are more common in shift workers and time zone travelers than in the general population, and diagnoses of irritable bowel syndromes (IBS) have been associated with sleep disturbances, occurring in 26 -55% of patients.…”