Folkhälsans Forskningscentrum

The gut microbiome may modify the associations between lifestyle factors and colorectal cancer (CRC) risk, but their complex interplay, including the interactions between lifestyle factors, remain underexplored. We examined associations between CRC-related lifestyle patterns and gut microbiome diversity and composition in Finnish adults. Our data included 1,228 adults aged 25-64years from the National FINRISK/FINDIET 2002 Study. Information on lifestyle and background factors was obtained through self-administered questionnaires. Dietary data were gathered using a 48-h dietary recall. CRC-related lifestyles were modelled using a CRC lifestyle index based on nine major risk factors for CRC. Lower index points reflected higher-risk lifestyles. The gut microbiome profiles were analyzed using shallow shotgun metagenome sequencing. Associations between the index and microbial diversity and composition were assessed using, e.g., linear regression and permutational multivariate ANOVA adjusted for relevant confounders. The index explained 0.2% of the variation in microbial composition between participants (p < 0.05). Higher-risk lifestyles for CRC were associated with lower microbial diversity (β 0.037, p 0.009). Higher-risk lifestyles were also associated with a higher relative abundance of species representing primarily the family Lachnospiraceae and genera such as Dorea and Mediterraneibacter, and lower relative abundance of species within the genus Bifidobacterium (< 0.0001). Participants with higher- and lower-risk lifestyles showed clear differences in their gut microbiome diversity and composition, higher-risk lifestyles being associated with potentially adverse microbial traits. These findings contribute to identifying microbial features that may characterize early stages of CRC development in individuals with high-risk lifestyles.

Primary osteoporosis can be caused by pathogenic variants in multiple genes. Recently, rare heterozygous variants in SGMS2, encoding SGMS2, have been identified to cause early-onset osteoporosis or more severe skeletal dysplasia. The incidence of pathogenic SGMS2 variants and their consequent clinical features, however, remain limited. This study aimed to identify the prevalence and nature of SGMS2 variants in Finnish patients with genetically undiagnosed idiopathic early-onset osteoporosis. All eleven exons and exon-intron boundaries of SGMS2 were sequenced. In a cohort of 44 patients (42 females and two males, median age at the time of recruitment 60 years, range 25-76 years), we identified one rare heterozygous missense variant (c.715T>C, p.Phe239Leu) and three intronic variants with unknown functional consequences; no pathogenic or likely pathogenic variants were found. Our results suggest that pathogenic variants in SGMS2 are not a common cause of early-onset idiopathic osteoporosis in Finnish patients. Further studies in larger cohorts and variable skeletal phenotypes are needed to increase our understanding of the role of SGMS2 in skeletal fragility.

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by immune dysregulation and epithelial barrier dysfunction. Although transcriptional changes in AD skin are increasingly well characterized, DNA methylation patterns remain less well understood. Here, we present an integrated analysis of matched DNA methylomes, transcriptomes, and microbiomes from lesional (n = 40), adjacent non-lesional (n = 38), and healthy control (n = 40) skin, using complementary cell-type-adjusted models. We identified thousands of differentially methylated regions (DMRs) across all pairwise contrasts (lesional vs. healthy: n = 13,514; lesional vs. non-lesional: n = 4591; non-lesional vs. healthy: n = 1716), including both hyper- and hypo-methylated regions with balanced effect sizes. A core subset of DMRs persisted after methylation-based adjustment, whereas the extensive lesional vs. non-lesional set was largely composition-driven. Integration with transcriptomic co-expression networks linked DMRs to immune-epithelial modules, and 225 DMR-gene pairs showed significant anti-correlation (FDR < 0.05). Lesional skin with dominant Staphylococcus aureus colonization differed at 92 DMRs compared with absent-colonized skin, of which 70 also overlapped with local severity. Pathway analyses consistently highlighted Rho GTPase and actin-junctional programs across analytic layers, suggesting that Rho GTPase signaling is a central integrator of immune, epithelial, and microbial interactions in AD. Our study underscores the importance of epigenomic remodeling in AD and highlights potential avenues for precision intervention in chronic inflammatory skin disease.

ABSTRACTThis study explored the reciprocal associations between maternal physical discipline and children's externalizing problems across childhood, distinguishing between trait‐like (i.e., between‐person) and state‐like (i.e., within‐person) differences. We used data from 604 dyads in Singapore, a context where physical discipline is commonly accepted. We analyzed maternal physical discipline and children's externalizing problems at three timepoints between ages 4 and 10.5 using a random‐intercept cross‐lagged panel model, adjusting for sociodemographic factors. At the between‐person level, maternal physical discipline covaried positively with more externalizing problems in children, supporting extensive evidence in the literature. However, at the within‐person level, maternal physical discipline at age 4.5 predicted children's lower externalizing problems at age 7. These findings underscore the value of disentangling between‐ and within‐person effects and highlight the complex associations between physical discipline and externalizing problems in a setting where physical discipline is common.

Few studies have compared gut hormone responses between bariatric procedures. This study compared Roux-en-Y and one-anastomosis gastric bypass (RYGB and OAGB) regarding glucagon-like peptide-1 (GLP-1), secretin, and glucose-insulin dynamics. This study included 41 participants (RYGB: n = 21, OAGB: n = 20) from the randomized RYSA trial with similar amounts of bypassed intestine between the procedures. Plasma GLP-1, secretin, glucose, insulin, and C-peptide were measured during a 360-min mixed-meal test before, and at 6- and 12-months after surgery. Outcomes included total and early-phase (0-60 min) areas under the curve (AUCs) and peak concentrations. Visual analogue scales were used to measure hunger and satiety. Both procedures resulted in ~25% weight loss and marked metabolic improvements over 12 months. While fasting GLP-1 remained largely unchanged, postprandial concentrations rose markedly at 6 months (total AUC increase in RYGB: ~330%, OAGB: ~259%; p < 0.001) and remained elevated at 12 months. The increases in early-phase GLP-1 AUC were 31% higher in RYGB than OAGB at 6 months (95% CI: 3 to 68; p = 0.030) and 25% higher at 12 months (95% CI: -2 to 59; p = 0.072). Peak GLP-1 increases were significantly higher ( ~ 32%) after RYGB at both follow-ups (p < 0.05). Postprandial reduction in hunger was greater after RYGB than OAGB from baseline to 12 months. Fasting or postprandial secretin concentrations showed no significant changes. Both operations were associated with decreased fasting glucose, insulin, and C-peptide; increased early glucose but decreased glucose total AUCs; and increased insulin early AUC and C-peptide total and early AUCs. Glucose early-phase AUC and peak concentration increases were greater after RYGB than OAGB. Both RYGB and OAGB lead to markedly enhanced postprandial GLP-1 responses, with no corresponding change in secretin levels. RYGB produces higher early postprandial increases in GLP-1 and glucose than OAGB, demonstrating that procedural differences can influence gut hormone and glucose responses.

Early life vitamin D levels may be associated with autism spectrum disorder (ASD) and related traits, but causality is unknown. We examine whether higher-than-standard vitamin D3 supplementation during the first 2 years, as well as higher pregnancy and childhood 25-hydroxyvitamin D (25(OH)D) levels and their trajectories, are associated with lower ASD trait scores at ages 6-8 years in a non-clinical cohort. This secondary analysis of the double-blind randomized clinical trial vitamin D intervention in infants (VIDI) comprised 366 Finnish children aged 6-8 years, 177 of whom were randomized to receive 400-IU and 189 to receive 1,200-IU daily oral vitamin D3 supplementation between ages 2 weeks and 2 years. ASD-related traits were assessed at mean age 7.2 years (SD 0.4) using the parent-reported Autism Spectrum Screening Questionnaire (ASSQ). Predictor variables were supplementation group, 25(OH)D concentrations measured during pregnancy and at ages 1 and 2 years, as well as 25(OH)D trajectories (high vs. low) derived from these time points. None of the predictor variables of interest were associated with the outcome in the full sample. After sex stratification, among boys, 25(OH)D concentrations at 1 and 2 years were inversely associated with ASSQ scores (mean difference -0.2 of normalized SD score (95% CI -0.3 to -0.1, p = .003) and -0.2 (95% CI -0.3 to -0.05, p = .01) per 10 ng/mL 25(OH)D) after adjustment for age, breastfeeding, parental education, maternal depressive symptoms, and season of 25(OH)D assessment as was belonging to the higher 25(OH)D trajectory, -0.45 SD (95% CI -0.79 to -0.10, p = .01). We found no indication that higher-than-normal vitamin D3 supplementation between ages 0 and 2 years decreases ASD-related trait scores at ages 6-8 years. Sex-stratified analysis suggested an inverse association, among boys, between early life 25(OH)D concentrations and ASD-related traits, warranting further studies on potential causal direction and sex specificity of associations.

ABSTRACT AIMS To assess changes in insulin secretion and sensitivity in diabetes subgroups (from cluster analysis), the stability of the subgrouping, and the association between steatotic liver disease (SLD), liver fibrosis (LF) and tissue insulin resistance. METHODS Participants from a regional diabetes register were studied within three years from diagnosis and 2-10 years later with fasting laboratory tests (n=547). A subset (n=194) participated in an investigation with i.v. glucagon-insulin tolerance test, and elastography. RESULTS Differences between subgroups attenuated during the follow-up. Obesity- and age-related subgroups (MOD &amp; MARD) were stable with &gt;76% retaining the same cluster, whereas that hold for &lt;25% in the groups characterized by insulin deficiency or resistance (SIDD &amp; SIRD). Despite stable BMI, HOMA2-IR decreased significantly, but remained highest, in SIRD. SLD/LF was most prevalent in SIRD (70%/42%) and MOD (60%/41%); BMI mainly explained the subgroup differences. Independently of BMI or SLD, LF was associated with insulin resistance in liver (OR 3.90 [95% CI 2.05-7.42]) and adipose tissue (1.14 [1.06-1.22]) and insulin sensitivity in muscle (0.33 [0.17-0.64]). CONCLUSIONS Subgrouping should be performed near diagnosis, as the more severe phenotypic features attenuate with time (or treatment). To assess the risk of LF, the degree of insulin resistance should be evaluated, not only BMI.