Gut microbiome and metabolic pathways linked to sleep quality.

Sleep quality is a vital determinant of human health as sleep disorders are associated with cognitive deficits, and chronic sleep deprivation is associated with a broad range of health complications. Previous studies on the association between the gut microbiome and sleep quality have been constrained by small sample sizes or have focused on specific sleep disorders, thus yielding inconsistent results. Herein, we investigated the relationship between microbial composition and sleep quality in a cohort of 159 Koreans. Sleep quality was measured using the Pittsburgh Sleep Quality Index (PSQI), determined through a self-administered questionnaire. Gut microbiome analyses were performed using 16S rRNA amplicons. We found no direct correlation between microbial alpha diversity metrics and sleep; however, we identified differences in beta diversity among sleep quality groups (with a PSQI score > 5 indicating poor sleep quality and PSQI ≤5 indicating good sleep quality). We also found differential microbial signatures (Bacteroides, Prevotella 9, and Faecalibacterium) among the groups. Furthermore, functional metabolic pathway profiles revealed significant linear correlations of the L-arginine and L-tryptophan biosynthetic pathways as well as 4-aminobutanoate degradation with sleep status. In particular, Faecalibacterium prausnitzii, which harbors these metabolic pathways, showed differences between sleep quality groups and a linear association with sleep quality scores and was thus identified as the species most strongly associated with sleep status. This study provides a significant advance in our understanding of the relationship between gut microbiota and sleep regulation. The current findings provide a basis for further research into potential therapeutic strategies for sleep disorders targeting the gut microbiome.

Exploring Stroke Risk through Mendelian Randomization: A Comprehensive Study Integrating Genetics and Metabolic Traits in the Korean Population.

Numerous risk factors play a role in the causation of stroke, and the cardiometabolic condition is a one of the most important. In Korea, various treatment methods are employed based on the constitutional type, which is known to differ significantly in cardiometabolic disease. In this study, we compared the estimates obtained for different groups by applying the Mendelian randomization method to investigate the causal effects of genetic characteristics on stroke, according to constitutional type. In clinical analysis, the subtypes differ significantly in diabetes or dyslipidemia. The genetic association estimates for the stroke subtype risk were obtained from MEGASTROKE, the International Stroke Genetics Consortium (ISGC), UKbiobank, and BioBank Japan (BBJ), using group-related SNPs as instrumental variables. The TE subtypes with higher risk of metabolic disease were associated with increased risk (beta = 4.190; s.e. = 1.807; p = 0.035) of cardioembolic stroke (CES), and the SE subtypes were associated with decreased risk (beta = -9.336, s.e. = 1.753; p = 3.87 × 10-5) of CES. The findings highlight the importance of personalized medicine in assessing disease risk based on an individual's constitutional type.

Elevated prevalence and treatment of sleep disorders from 2011 to 2020: a nationwide population-based retrospective cohort study in Korea.

OBJECTIVES: This study used National Health Insurance claims data from Korea to report the prevalence of sleep disorders and treatment status, including traditional Korean medicine, in the last 10 years. METHODS: This is a retrospective cohort study in Korea. All diagnosis and prescription data, including herbal medicine claims, from the Health Insurance Review and Assessment Service from 2011 to 2020 were reviewed. Prevalence estimation, direct medical expenses and prescribed amounts for sleep disorders were recorded. RESULTS: The prevalence of sleep disorders increased from 3 867 975 (7.62%) in 2011 to 7 446 846 (14.41%) in 2020, nearly doubling over 10 years. Insomnia was observed in 91.44% (n=9 011 692) of the patients. The mean number of hospital visits per patient for sleep disorders was 11.5 (±26.62). Benzodiazepines are the most commonly prescribed medications for sleep disorders, and gamma-isoyosan is the most frequently prescribed herbal medicine. CONCLUSIONS: Sleep disorders are continuously increasing, as is the use of medical services-personal and social medical expenses are also increasing accordingly. Sleep disorders should be recognised as a significant health problem that needs to be actively addressed to improve quality of life.

Characteristics of insulin resistance in Korean adults from the perspective of circadian and metabolic sensing genes.

BACKGROUND: The biological clock allows an organism to anticipate periodic environmental changes and adjust its physiology and behavior accordingly. OBJECTIVE: This retrospective cross-sectional study examined circadian gene polymorphisms and clinical characteristics associated with insulin resistance (IR). METHODS: We analyzed data from 1,404 Korean adults aged 30 to 55 with no history of cancer and cardio-cerebrovascular disease. The population was classified according to sex and homeostasis model assessment of insulin resistance (HOMA-IR) values. Demographics, anthropometric and clinical characteristics, and single nucleotide polymorphisms (SNPs) were analyzed with respect to sex, age, and HOMA-IR values. We used association rule mining to identify sets of SNPs from circadian and metabolic sensing genes that may be associated with IR. RESULTS: Among the subjects, 15.0% of 960 women and 24.3% of 444 men had HOMA-IR values above 2. Most of the parameters differed significantly between men and women, as well as between the groups with high and low insulin sensitivity. Body fat mass of the trunk, which was significantly higher in insulin-resistant groups, had a higher correlation with high sensitivity C-reactive protein and hemoglobin levels in women, and alanine aminotransferase and aspartate aminotransferase levels in men. Homozygous minor allele genotype sets of SNPs rs17031578 and rs228669 in the PER3 gene could be more frequently found among women with HOMA-IR values above 2 (p = .014). CONCLUSION: Oxidative stress enhanced by adiposity and iron overload, which may also be linked to NRF2 and PER3-related pathways, is related to IR in adulthood. However, due to the small population size in this study, more research is needed.

Regulation of CIRP by genetic factors of SP1 related to cold sensitivity.

Cold-inducible RNA-binding-protein (CIRP) is a cold shock protein that plays a protective role in genotoxic stress response. CIRP modulates inflammation in human diseases, inhibits cell proliferation, and protects cells from genotoxic damage during cellular stress. The mild cold responsive element and specificity protein 1 (SP1) play a role in Cirp expression at low temperatures. Although previous studies have provided insights into the immune functions of SP1 or CIRP, the mechanisms by which CIRP and SP1 me diate inflammatory responses remain largely unknown. Therefore, in the current study, we examined whether Cirp expression is affected by genetic factors related to temperature sensitivity as well as under low temperature. We performed a genome-wide association study on cold sensitivity in 2,000 participants. Fifty-six genome-wide significant trait-locus pairs were identified (p<1×10-5, false discovery rate < 0.05). Among these variants, rs1117050 and rs11170510 had a strong linkage disequilibrium (r2 > 0.8) relationship and expression quantitative trait locus-associated signals with the nearest Sp1 gene. We confirmed that the minor alleles of rs11170510 and rs58123204 were associated with increased Sp1 expression. Additionally, Sp1 overexpression led to CIRP translocation from the nucleus to the cytoplasm. CIRP protein levels increased in serum samples that had minor alleles of rs11170510 and rs58123204. Levels of various pro-inflammatory cytokines were also significantly increased in human peripheral blood mononuclear cells with minor alleles of rs11170510 and rs58123204. These results suggest that genetic factors related to cold sensitivity regulate CIRP expression and function and provide valuable insights into prediction of potential diseases through analysis of inherent genetic factors in humans.

Supplementary data for genome-wide DNA methylation and gene expression analysis of PBMCs in patients with metabolic syndrome.

This supplementary data supports the research article 'Genome-wide DNA methylation profiling reveals candidate biomarkers and probable molecular mechanism of metabolic syndrome' (Baek et al., in press). To obtain these data, 32 participants with metabolic syndrome (MetS) were enrolled in the associated study. We collected peripheral blood mononuclear cells (PBMCs) from 11 patients with MetS and nine controls and compared genome-wide gene expression and DNA methylation signatures. The remaining 12 participants were used for the experimental validation of the candidate groups. We provide the raw, analyzed, and filtered genome-wide DNA methylation data, obtained using the Infinium Human MethylationEPIC BeadChIP array, and whole transcriptome sequencing data (accession number GSE181647). We list the differentially expressed and differentially methylated genes and their biological functions. These data can serve as a basis for screening appropriate epigenetic biomarkers for MetS.