Sleep is a fundamental biological process, that when repeatedly disrupted, can result in severe health consequences. Recent studies suggest that both sleep fragmentation (SF) and dysbiosis of the gut microbiome can lead to metabolic disorders, though the underlying mechanisms are largely unclear. To better understand the consequences of SF, we investigated the effects of acute (6 days) and chronic (6 weeks) SF on rats by examining taxonomic profiles of microbiota in the distal ileum, cecum and proximal colon, as well as assessing structural and functional integrity of the gastrointestinal barrier. We further assayed the impact of SF on a host function by evaluating inflammation and immune response. Both acute and chronic SF induced microbial dysbiosis, more dramatically in the distal ileum (compared to other two regions studied), as noted by significant perturbations in alpha-and beta-diversity; though, specific microbial populations were significantly altered throughout each of the three regions. Furthermore, chronic SF resulted in increased crypt depth in the distal ileum and an increase in the number of villi lining both the cecum and proximal colon. Additional changes were noted with chronic SF, including: decreased microbial adhesion and penetration in the distal ileum and cecum, elevation in serum levels of the cytokine KC/GRO, and depressed levels of corticotropin. Importantly, our data show that perturbations to microbial ecology and intestinal morphology intensify in response to prolonged SF and these changes are habitat specific. Together, these results reveal consequences to gut microbiota homeostasis and host response following acute and chronic SF in rats.

Interrupted sleep alters gut microbiota profile and function

PurposeBlood Alcohol Levels (BAL) correlate with alcohol intoxication and tolerance. In this study we correlated concentrations of Fatty Acid Ethyl Esters (FAEEs) with BAL and examined the effects of gender and age.MethodsThis study was approved by the Colorado Multiple Institutional Review Board for monitoring of human research. Samples for inclusion in this study were identified by positive BAL. Samples positive for BAL (N=48, men=38, women=10) were labeled with years of age, BAL and gender (without patient identifiers) and analyzed for FAEEs by gas chromatography-mass spectrometry (GC-MS).ResultsAll forty-eight samples with positive BAL had measurable FAEE levels. BAL correlated with individual FAEEs (ethyl palmitate, ethyl oleate, and ethyl stearate, Spearman's rank r=0.73-0.77, p≤0.001) and total FAEEs (Spearman's rank r=0.77, p≤0.001). Patients with BAL≥100 mg/dL (intoxicated) or BAL≥200 mg/dL (tolerant) had total FAEE concentration greater than 3000 nM (Fisher's exact: 4.38, p≤0.0001 and 4.75, p≤0.00001, respectively). Mean BAL was not significantly different by gender (218.68±114.32 mg/dL for men, 174.9±113.90 mg/dL for women, p=0.29). Total FAEE concentration was 8513.1±5999.1 nM for men and 4880.8±4259.5 nM for women. Controlling for blood ethanol levels and age in an ANCOVA on the rank transformation of total FAEEs, gender was not a statistically significant covariate (p=0.12). Divided into two groups by median age (43.5 years), total FAEE concentration was 9591.9±5772.5 nM for the younger group and 5920.9±5402.3 nM for the older group. Mean BAL was significantly different by age (245.21±96.832 mg/dL for the younger group, 173.92±121.39 mg/dL for the older group, p=.01). Controlling for blood ethanol levels and gender in an ANCOVA on the rank transformation of total FAEEs, age was not a statistically significant covariate (p=0.07).ConclusionThe strong correlations between BAL and FAEE levels confirm the utility of plasma FAEE levels as an indication of BAL. In addition, plasma FAEE levels greater than 3000 nM correlated with BAL consistent with intoxication and tolerance. Our analysis failed to demonstrate a significant relationship between gender or age and FAEE levels.

The decline was highest for American Indians (from 24.7 to 13.3 per 100,000) followed by Hispanics (from 21.4 to 12.9 per 100,000) and NHW (from 7.9 to 5.2 per 100,000). For each of the ethnic groups, age-adjusted incidence rates were higher in males than females. The greatest decline in age-adjusted incidence rates was seen in American Indian males (from 34.3 to 16.5 per 100,000). The age-specific incidence rates decreased over time among all groups, with the exception of American Indian females aged 50-59 (from 4.1 to 15.9 per 100,000) and 60-69 (from 17.5 to 29.7 per 100,000). The incidence of gastric cancer increased with age for each of the ethnic groups. The intestinal type of gastric cancer was more common than the diffuse type. The percentage of intestinal-type gastric cancers declined over time, while the percentage of diffuse-type gastric cancers increased, irrespective of ethnic group or gender. The intestinal type was more common in males than females for each of the ethnic groups. Conclusions: Gastric cancer incidence rates have steadily declined among New Mexico's three major ethnic groups over the past 28 years. The greatest rate of decline has been observed within the American Indian population, particularly the males.The percentage of diffuse-type gastric cancers has progressively increased, while the percentage of intestinal-type gastric cancers has progressively decreased.