INTRODUCTION
Atopic dermatitis (AD) is a long-lasting, relapsing pruritic inflammatory skin disorder that occurs in both childhood and adulthood. It leads to a defective skin barrier and strengthened T-cell responses to allergens and microbes from surroundings, resulting in chronic inflammatory reaction.1 In the past few years, the prevalence of atopic dermatitis has increased rapidly in developed countries such as the United States2 and in Taiwan.3 AD not only increases social, financial, and psychological burdens4, but also makes a deleterious effect on quality of life, 5 and is associated with comorbidities.6
Interestingly, there is growing evidence showing an association between AD and constipation, a common condition affecting children and adults worldwide and a frequent reason for visits to gastroenterologists. The mean global prevalence of constipation in adults is 16% and that in children is 12%.7 Although constipation has few life-threatening complications, it can affect physical and emotional distress for patients and their family members, eventually impairing quality of life. Complications of constipation included hemorrhoids, fecal incontinence, and rectal prolapse, which often increases the frequency of outpatient department visits or hospitalizations, resulting in increased cost of health insurance.
Constipation is now considered to be a causative factor in gut dysbiosis8 and therapeutic approaches are increasingly incorporating probiotics, prebiotics, or synbiotics with a view to manipulating the intestinal microbiota.9 In addition, recent study has demonstrated that the gut microbiota might exert important regulatory effects via the gut-skin axis.10For example, intestinal dysbiosis and lower concentration of short-chain fatty acids (SCFAs) in the bowel are found in patients with AD.11–14 In a Korean study, which investigated the gut microbiome and relevant metabolites in patients with AD, dysbiosis of Faecalibacterium prausnitzii was observed in stool samples of patients with AD. This condition decreases the production of propionate and butyrate, resulting in the dysregulation of intestinal inflammation and the defect of the epithelial barrier (leaky gut), thereby allowing penetration of toxin and microbes into systemic circulation, which activates Th2 immune responses, eventually culminating in skin damage.12 Some researches have suggested that allergic disease might be connected with constipation.15,16Furthermore, previous research has indicated that prolonged stool stasis may change the intestinal environment and microbiota, resulting in deleterious effects on gut motility and mucosal immunity.17,18 Whether constipation predisposes susceptible individuals to AD is unknown. Currently, there are scanty data on the association between constipation and AD in the literature. Moreover, this relationship has never been investigated by data obtained from the large national longitudinal database. We hypothesized that constipation could impact the risk of AD and evaluated this hypothesis by analyzing the population-based retrospective cohort from Taiwanese National Health Insurance Research Database (NHIRD).