Sleep disorders related to nutrition and digestive diseases: a neglected clinical condition

Abstract

Sleep disturbances often result from inappropriate lifestyles, incorrect dietary habits, and/or digestive diseases. This clinical condition, however, has not been sufficiently explored in this area. Several studies have linked the circadian timing system to the physiology of metabolism control mechanisms, energy balance regulation, and nutrition. Sleep disturbances supposedly trigger digestive disorders or conversely represent specific clinical manifestation of gastrointestinal (GI) diseases. Poor sleep may worsen the symptoms of GI disorders, affecting the quality of life. Conversely, short sleep may influence dietary choices, as well as meal timing, and the circadian system drives temporal changes in metabolic patterns. Emerging evidence suggests that patients with inappropriate dietary habits and chronic digestive disorders often sleep less and show lower sleep efficiency, compared with healthy individuals. Sleep disturbances may thus represent a primary symptom of digestive diseases. Further controlled trials are needed to fully understand the relationship between sleep disturbances, dietary habits, and GI disorders. It may be also anticipated that the evaluation of sleep quality may prove useful to drive positive interventions and improve the quality of life in a proportion of patients. This review summarizes data linking sleep disorders with diet and a series of disease including gastro-esophageal reflux disease, peptic disease, functional gastrointestinal disorders, inflammatory bowel diseases, gut microbiota alterations, liver and pancreatic diseases, and obesity. The evidence supporting the complex interplay between sleep dysfunction, nutrition, and digestive diseases is discussed.

Keywords: circadian rhythm; diet; digestive diseases; gastrointestinal disease; nutrition; sleep disorders.

Figure 1

Bidirectional interaction between GI tract, liver, pancreas, and brain: food and gut-brain connection. The central nervous system (CNS) plays a role in regulating function and homeostasis of the gastrointestinal tract. Nutrients affect the production of hormones, including growth hormone, prolactin, testosterone, melatonin, and serotonin, all playing a role in the regulation of the circadian rhythms and brain function. Similarly, digestive hormones and enteroendocrine secretions (GLP-1, GIP, serotonin, substance P and peptide YY) also activate visceral afferent endings. Pancreatic endocrine secretion, through glucose homeostasis, insulin-resistance and GLP-1 activity is also implicated in the crosstalk between gut and neurological function. Impairment of liver detoxifying processes results in increased concentrations of false neurotransmitters and CNS-acting toxins. The gut flora also influences the CNS, regulating the architecture of sleep, stress reactivity and behavior. Bacterial metabolic products and inflammatory cytokines have been proposed as possible mediators. Adapted from E. M. Candeias et al. World J Diabetes 2015;6:807-827.

Figure 2

Bidirectional interaction among the gut microbiota and the brain. The gut microbiome affects the brain through a variety of mechanisms, producing or modifying several metabolites, neuroactive substances and cytokines. On the other hand, the Enteric Nervous System, receiving efferent information from the brain through autonomic neural connections and hormonal pathways, modulates gastrointestinal motor function, gastric secretion, intestinal absorption and secretion and gut-associated immune system, which all may impact on the composition and metabolism of the gut flora. SCFAs: Short Chain Fatty Acids. Adapted from Chen X, Protein Cell 2013;4:403-14.

Figure 3

Underlying mechanisms of hepatic encephalopathy. Neuroinflammation is common in hepatic encephalopathy. It has been suggested that hyperammonaemia as well as systematic inflammation may lead to the activation of microglia. This activation induces to the local production of inflammatory mediators, that along with hyperammonaemia, negatively impact astrocyte function and contribute to the neurobehavioral deficits in hepatic encephalopathy. Adapted from Butterworth RF, Nat Rev Gastroenterol Hepatol 2013;10:522-528.

Figure 4

Effect of alcoholic and non-alcoholic steatohepatitis on brain function. High caloric and fat-rich diet and alcohol are the main causes of non-alcoholic and alcoholic steatohepatitis, which are proven to have a negative impact on brain function. Insulin plays an important role in both these conditions, compromising neural cell survival, metabolism and plasticity. In steatohepatitis the increased production of toxic lipids (e.g. ceramide), oxidative stress, as well as local cytokine production and activation, along with direct alcohol toxicity and depressant activity, may induce sleep disturbances, cognitive impairment and neurodegeneration.