Despite the established importance of the human microbiome in health, the integrated microbial exposures occurring within the sleep environment remain poorly understood. Sleep represents a critical period of prolonged exposure to indoor microbial reservoirs, yet no study has simultaneously examined the connectivity between environmental sources and the human oral microbiome. We present a novel, tri-source microbiome dataset characterizing microbial communities from co-located saliva, pillow dust, and bedroom air collected from healthy participants in real-world sleep environments. Samples were collected under standardized protocols and analyzed using 16S rRNA gene amplicon sequencing (V3-V4 region). Rigorous quality control and bioinformatic processing were applied to generate high-resolution amplicon sequence variants. Alpha diversity analysis revealed that pillow dust serves as the most diverse and stable microbial reservoir, exhibiting significantly higher species richness and phylogenetic diversity than saliva or air (p < 0.05). Beta diversity analysis showed distinct clustering by sample type, with indoor air and pillow dust exhibiting closer microbial similarity to each other than to saliva. Notably, significant genus-level correlations were identified between air and pillow dust (e.g., Brevitalea, Gardnerella) and between pillow dust and saliva (e.g., Actinomyces, Bifidobacterium), suggesting potential microbial exchange through gravitational settling and physical contact. This tri-source dataset provides a unique resource for investigating host-environment microbial interactions during rest. Our findings highlight the sleep environment as a significant exposome factor that may influence oral microbiome dynamics, offering new avenues for research into respiratory health, built environment science, and human exposome studies.
INTRODUCTION:Female reproductive traits influence bone mineral density (BMD) and fracture risks through estrogen exposure. However, these causal relationships remain unclear due to confounding. Understanding these relationships is crucial for osteoporosis prevention strategies. This study aimed to investigate the causal impact of age at natural menopause (ANM) and age at menarche (AAM) on BMD and osteoporosis risk, and to explore gene-exercise interactions influencing bone health in East Asian women. METHODS:We conducted two-sample Mendelian randomization (MR) using 15 genetic variants for AAM and 36 variants for ANM in 51,049 women from the Taiwan Biobank, split into discovery (n = 25,549) and validation (n = 25,500) cohorts. Outcomes were BMD Z scores, T scores, and clinical osteoporosis. We performed univariable and multivariable MR, followed by regression analyses, focusing on exercise effects on BMD and genetic predisposition scores for AAM and ANM. RESULTS:In multivariable MR, genetically determined later ANM was associated with higher BMD Z scores (β = 0.045, 95% confidence interval [0.021, 0.069]), higher T scores (β = 0.046, [0.020, 0.072]), and lower osteoporosis risk (β = -0.106, [-0.154, -0.058]). No consistent causal effect was observed for AAM due to genetic pleiotropy. ANM polygenic risk score and regular exercise were independently associated with improved BMD Z- and T scores and reduced risk of osteoporosis. Specific gene-exercise interactions were identified in which the AAM polygenic risk score interacted significantly with gymnastics, while the ANM polygenic risk score interacted with lower-limb exercise and swimming. CONCLUSION:Late ANM provides causal protection against osteoporosis in East Asian women, while the effects of AAM remain insignificant. Exercise benefits bone health with activity-specific genetic interactions. These findings support personalized osteoporosis prevention strategies incorporating both genetic risk assessment and targeted exercise recommendations, particularly for women with early menopause predisposition.
Background: Celiac disease (CeD) is a chronic, immune-mediated condition driven by dietary gluten in genetically predisposed individuals, primarily those carrying HLA-DQ2 and HLA-DQ8. Unlike other autoimmune diseases, CeD offers an exceptional degree of mechanistic clarity, stemming from the identification of the main environmental driver, gluten, and its link with genetic susceptibility. Summary: While gluten and HLA genotype are necessary for developing CeD, they are not sufficient. Emerging research highlights that environmental and lifestyle factors, including early-life ecosystem, infections, and gut microbiota, critically modulate CeD risk and severity. This review synthesizes emerging insights and focuses on the role of the intestinal epithelium not just as target of immune-mediated injury but as an active interface integrating genetic susceptibility with environmental cues. Recent data reveal that intestinal epithelial cells can release tissue transglutaminase 2 that modifies gluten peptide antigenicity, participate in antigen presentation and immune signaling, and respond to microbial and dietary factors, positioning them as contributors to CeD initiation and progression. The review also highlights knowledge gaps and areas of active debate in CeD. Key Messages: CeD has a main environmental driver (gluten) and a defined genetic susceptibility, linked to major histocompatibility complex class II DQ2 and DQ8. Activation of the CD4+ T-cell response by gluten and cytotoxic transformation of intraepithelial lymphocytes culminate in villus atrophy of the proximal small intestine. In this opinion-based perspective, we integrate and review recent evidence suggesting the intestinal epithelium plays an active role in CeD initiation and/or progression, which could lead to strategies to prevent or better treat this condition.
INTRODUCTION:Breast cancer (BC) is the most frequent cancer in women, driven by a combination of genetic, environmental, and lifestyle factors. Whether modifiable sleep behaviors causally affect BC risk remains unclear. Aims of the study were to systematically assess the causal impact of sleep-related phenotypes on overall BC and its major subtypes using two-sample mendelian randomization (MR) and to determine whether inflammatory proteins mediate these relationships. METHODS:Inverse variance weighted served as the main analysis, with sensitivity and reverse-MR analyses as supporting checks. Mediation was quantified with a two-step MR design. RESULTS:Morning chronotype significantly reduced the risk of overall BC (OR = 0.936, 95% CI: 0.893-0.980) and luminal A subtype (OR = 0.944, 95% CI: 0.894-0.996). Short sleep duration was associated with decreased risk of overall BC (OR = 0.482, 95% CI: 0.284-0.818) and luminal A subtype (OR = 0.385, 95% CI: 0.194-0.766), whereas long sleep duration increased the risk of triple-negative BC (OR = 9.433, 95% CI: 2.419-36.775) and luminal A subtype (OR = 2.186, 95% CI: 1.111-4.302). Mediation analysis indicated that CXCL11 accounted for 22.4% of the total causal effect of short sleep duration on luminal A BC. CONCLUSION:Morning chronotype confers protection against BC, whereas prolonged sleep duration elevates the risk of triple-negative and luminal A BC. CXCL11 mediates part of the protective effect of short sleep on luminal A BC. These findings provide evidence-based support for BC prevention strategies focusing on sleep optimization.
INTRODUCTION:Type 2 diabetes (T2D) risk factors are associated with gut microbiota dysregulation that can alter circulating metabolite levels such as bile acids (BAs) and short-chain fatty acids (SCFAs). The objective was to investigate how the high dairy (HD) (≥4 servings/day) product intake compared to adequate dairy (AD) (≤2 servings/day) intake influences the correlations between Roseburia, Faecalibacterium, Flavonifractor, as well as Verrucomicrobia and circulating BAs and SCFAs in subjects at risk of T2D. METHODS:In a randomized crossover trial, 10 hyperinsulinemic adults were randomized to HD or AD for 6 weeks separated by a 6-week washout period. Gut microbiota were measured with 16S rRNA-based high-throughput sequencing. BA profiling in plasma was performed by high-performance liquid chromatography-tandem mass spectrometry. Serum SCFAs were determined using headspace gas chromatography. RESULTS:No significant differences were observed in mean circulating BA or SCFA levels between AD and HD consumption. Verrucomicrobia and Flavonifractor showed positive correlations with secondary BAs following HD and AD intake, respectively. Additionally, Flavonifractor correlated positively with acetic and propionic acids after HD intake. Roseburia correlated positively with primary BAs, propionate, and butyrate after HD intake. Faecalibacterium was positively correlated with cholic acid after AD intake and with hexanoic acid after HD intake. CONCLUSION:These findings suggest that HD intake may modulate microbiota-metabolite interactions without altering circulating metabolite concentrations, highlighting a potential role for dietary patterns in shaping gut-derived metabolic signals in individuals at risk of T2D.
