Integrated analysis of the microbiota-gut-brain axis in response to sleep deprivation and diet-induced obesity

Abstract

IntroductionSleep deprivation (SD) and obesity are common in modern societies. SD and obesity frequently coexist, but research on the combined consequences of SD and obesity has been limited. In this study, we investigated the gut microbiota and host responses to SD and high-fat diet (HFD)-induced obesity. In addition, we attempted to identify key mediators of the microbiota-gut-brain axis.MethodsC57BL/6J mice were divided into four groups based on whether they were sleep deprived and whether they were fed a standard chow diet (SCD) or HFD. We then performed fecal microbiome shotgun sequencing, gut transcriptome analysis using RNA sequencing, and brain mRNA expression analysis using the nanoString nCounter Mouse Neuroinflammation Panel.ResultsThe gut microbiota was significantly altered by the HFD, whereas the gut transcriptome was primarily influenced by SD. Sleep and diet are both important in the inflammatory system of the brain. When SD and the HFD were combined, the inflammatory system of the brain was severely disrupted. In addition, inosine-5' phosphate may be the gut microbial metabolite that mediates microbiota-gut-brain interactions. To identify the major drivers of this interaction, we analyzed the multi-omics data. Integrative analysis revealed two driver factors that were mostly composed of the gut microbiota. We discovered that the gut microbiota may be the primary driver of microbiota-gut-brain interactions.DiscussionThese findings imply that healing gut dysbiosis may be a viable therapeutic target for enhancing sleep quality and curing obesity-related dysfunction.

Sleep Deprivation and Gut Microbiota Dysbiosis: Current Understandings and Implications

“…SD has been proved to increase Aβ-in the hippocampus, precuneus, thalamus, and cortex, along with neuroinflammation and oxidative stress, and inhibit cholinergic neurons, indicating a direct connection between SD and neuropathological events associated with AD [113]. (3) Stroke: a study showed that SD exacerbates stroke by raising the expression of growth-inhibiting genes, neuroinflammation, and oxidative stress [28,113].…”

“…Previous research has found that 20% to one-quarter of the population of the United States is forced to face it [16][17][18] because of improper diet [19], pressure [20,21], and increasing brain stimulation by smartphones [1]. Possible adverse outcomes elicited by SD include depression (in a bidirectional relationship with SD) [22][23][24][25][26], obesity [27,28], diabetes [14,29], cardiovascular disease [30,31], cancer [32,33], neurological dysfunction [31,34], and even death [34]. Therefore, a better understanding of the association between SD and human diseases, as well as the underlying mechanisms of action, is of critical importance.…”

Lifestyle patterns influence the composition of the gut microbiome in a healthy Chinese population

“…According to the consensus of the American Academy of Sleep Medicine and Sleep Research Society, adults should strive for 7 h of nightly sleep while young adults require 9 h. Insufficient sleep due to occupational or recreational activities is classified as sleep deprivation 101 . One study has demonstrated a correlation between sleep deprivation and the gut dysbiosis 102 . In this study, increased sleep deprivation decreased the alpha diversity of the gut microbiome (Supplementary Table 13 )although the differences were not significant, and the gut microbiota structures among the normal sleep (n = 145), more sleep deprivation (n = 131) and less sleep deprivation (n = 207) groups showed a significant difference (Binary-jaccard distance, Adonis, Pr (> F) = 0.029, Fig.…”

Impact of parental body mass index at diagnosis on obesity in survivors of pediatric craniopharyngioma

“…Hypothalamic syndrome is also characterized by abnormal eating behavior such as hyperphagia 5 . Patients with hypothalamic lesions often present with higher food inattention, lower statiety and higher restrained eating behavior 7 . However, hyperphagia is not always present in patients with CP, reflecting that in some patients specific hypothalamic nuclei are still intact after treatment 2 .…”