Sleepy, leaky gut

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Science Translational Medicine  02 Nov 2016:
Vol. 8, Issue 363, pp. 363ec177
DOI: 10.1126/scitranslmed.aai9168

Sleep fragmentation is characterized by frequent arousals from sleep. It is common in human populations and may occur without shifts in circadian rhythms or decreased overall sleep time. Sleep disturbances, such as from sleep fragmentation, are associated with metabolic and inflammatory changes in humans and animal models. The mechanisms driving the effects of sleep fragmentation on systemic processes remain unclear. Recent studies have shown that the gut microbiome interacts with inflammatory, metabolic, and circadian clock systems. Further, hypoxia mimicking obstructive sleep apnea, a known cause of sleep fragmentation, alters the gut microbiome.

To explore the relationships between sleep fragmentation, gut microbiota, inflammation, and metabolism, Poroyko et al. subjected mice to sleep fragmentation for 4 weeks followed by a 2-week recovery period. Taxonomic profiles of the fecal microbiota were determined before and after sleep fragmentation, and multiple factors related to inflammation and metabolism, including insulin sensitivity, leptin, and interleukin-6 were measured. Food intake, fat mass, and metabolic disturbance increased in the sleep fragmented mice. There was decreased tissue-specific and systemic insulin sensitivity, increased leptin, and increased inflammatory markers. Reversible changes in the fecal microbiota, such as an increase in Lachnospiraceae and Ruminococcaceae and a decrease in Lactobacillaceae families, were also seen.

Transplanting gut flora from sleep-fragmented mice into non–sleep fragmented mice replicated the inflammatory and metabolic changes seen in sleep fragmentation, suggesting that the inflammatory and metabolic changes were mediated by changes in the gut microbiota. To test a potential mechanism by which this process might occur, fecal water from sleep fragmented mice was applied in vitro to colonic epithelium and was found to increase permeability. This increased permeability is a potential pathway for microbial products to enter the systemic circulation and stimulate an inflammatory response that may mediate the metabolic dysfunctions associated with chronic sleep fragmentation.

Poroyko et al. concluded that sleep fragmentation–induced metabolic alterations may be mediated in part by concurrent changes in gut microbiota. These findings suggest a mechanism to explain the inflammatory and metabolic changes seen in humans with sleep disturbances. Rather than improve sleep fragmentation, fecal microbiota may be targeted with therapeutics to ameliorate the adverse effects of sleep fragmentation—but such therapies require in vivo testing in animal models before translation to human subjects.

V. A. Poroyko et al., Chronic sleep disruption alters gut microbiota, induces systemic and adipose tissue inflammation and insulin resistance in mice. Sci. Rep. 10.1038/srep35405 (2016). [Full Text]

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