Sleep and Microbes

Abstract

Sleep is profoundly altered during the course of infectious diseases. The typical response to infection includes an initial increase in nonrapid eye movement sleep (NREMS) followed by an inhibition in NREMS. REMS is inhibited during infections. Bacterial cell wall components, such as peptidoglycan and lipopolysaccharide, macrophage digests of these components, such as muramyl peptides, and viral products, such as viral double-stranded RNA, trigger sleep responses. They do so via pathogen-associated molecular pattern recognition receptors that, in turn, enhance cytokine production. Altered sleep and associated sleep-facilitated fever responses are likely adaptive responses to infection. Normal sleep in physiological conditions may also be influenced by gut microbes because the microbiota is affected by circadian rhythms, stressors, diet, and exercise. Furthermore, sleep loss enhances translocation of viable bacteria from the intestine, which provides another means by which sleep-microbe interactions impact neurobiology.

Keywords: Bacteria; Cytokine; Fever; Gut microbiota; LPS; Peptidoglycan; Sleep; Sleep loss; Viruses.

Fig. 1

Pathway for intestinal bacteria to affect sleep. From left to right: intestinal bacteria, and/or bacteria cell wall degradation products, such as muramyl peptides (MPs) or lipopolysaccharide (LPS), translocate across the intestinal epithelial barrier. Sleep loss and several conditions that affect sleep, e.g., injury, food intake, stress, circadian rhythm, and exercise, affect bacteria translocation. Bacteria are engulfed by phagocytes, such as macrophages or neutrophils, and digested; digest products (e.g., MPs, LPS) are released into the surrounding intercellular fluid. MPs and LPS in turn activate phagocytes (illustrated by the jagged cell membrane) that then release cytokines such as interleukin-1 and tumor necrosis factor. Systemic cytokines access the brain by at least two routes. Cytokines can signal the brain via vagus nerve afferents whose action potentials induce further cytokine production in the brain by glia and neurons. Cytokines can also cross the blood–brain barrier (BBB) to induce their own and other cytokine productions. Brain cytokines at low concentrations enhance sleep, while at high concentrations fragment sleep. Other microbes, e.g., viruses, and their components also enhance cytokine production via endogenous receptors that recognize pathogen-associated molecular patterns, e.g., Toll-like receptors, to affect sleep (not illustrated).