Oral microbiota of adolescents with dental caries:A systematic review

Objective: This systematic review summarizes the current knowledge on the association between the oral microbiota and dental caries in adolescents. Design: An electronic search was carried out across five databases. Studies were included if they conducted research on generally healthy adolescents, applied molecular-based microbiological analyses and assessed caries status. Data extraction was performed by two reviewers and the Newcastle-Ottawa Scale was applied for quality assessment. Results: In total, 3935 records were reviewed which resulted in a selection of 20 cross-sectional studies (published 2005–2022) with a sample size ranging from 11 to 614 participants including adolescents between 11 and 19 years. The studies analyzed saliva, dental biofilm or tongue swabs with Checkerboard DNA-DNA hybridization, (q)PCR or Next-Generation Sequencing methods. Prevotella denticola, Scardoviae Wiggsiae, Streptococcus sobrinus and Streptococcus mutans were the most frequently reported species presenting higher abundance in adolescents with caries. The majority of the studies reported that the microbial diversity was similar between participants with and without dental caries. Conclusion: This systematic review is the first that shows how the oral microbiota composition in adolescents appears to differ between those with and without dental caries, suggesting certain taxa may be associated with increased caries risk. However, there is a need to replicate and expand these findings in larger, longitudinal studies that also focus on caries severity and take adolescent-specific factors into account.</p

Oral microbiota of adolescents with dental caries:A systematic review

Objective: This systematic review summarizes the current knowledge on the association between the oral microbiota and dental caries in adolescents. Design: An electronic search was carried out across five databases. Studies were included if they conducted research on generally healthy adolescents, applied molecular-based microbiological analyses and assessed caries status. Data extraction was performed by two reviewers and the Newcastle-Ottawa Scale was applied for quality assessment. Results: In total, 3935 records were reviewed which resulted in a selection of 20 cross-sectional studies (published 2005–2022) with a sample size ranging from 11 to 614 participants including adolescents between 11 and 19 years. The studies analyzed saliva, dental biofilm or tongue swabs with Checkerboard DNA-DNA hybridization, (q)PCR or Next-Generation Sequencing methods. Prevotella denticola, Scardoviae Wiggsiae, Streptococcus sobrinus and Streptococcus mutans were the most frequently reported species presenting higher abundance in adolescents with caries. The majority of the studies reported that the microbial diversity was similar between participants with and without dental caries. Conclusion: This systematic review is the first that shows how the oral microbiota composition in adolescents appears to differ between those with and without dental caries, suggesting certain taxa may be associated with increased caries risk. However, there is a need to replicate and expand these findings in larger, longitudinal studies that also focus on caries severity and take adolescent-specific factors into account.</p

Bi-Directional Interactions between Glucose-Lowering Medications and Gut Microbiome in Patients with Type 2 Diabetes Mellitus: A Systematic Review

Background: Although common drugs for treating type 2 diabetes (T2D) are widely used, their therapeutic effects vary greatly. The interaction between the gut microbiome and glucose-lowering drugs is one of the main contributors to the variability in T2D progression and response to therapy. On the one hand, glucose-lowering drugs can alter gut microbiome components. On the other hand, specific gut microbiota can influence glycemic control as the therapeutic effects of these drugs. Therefore, this systematic review assesses the bi-directional relationships between common glucose-lowering drugs and gut microbiome profiles. Methods: A systematic search of Embase, Web of Science, PubMed, and Google Scholar databases was performed. Observational studies and randomised controlled trials (RCTs), published from inception to July 2023, comprising T2D patients and investigating bi-directional interactions between glucose-lowering drugs and gut microbiome, were included. Results: Summarised findings indicated that glucose-lowering drugs could increase metabolic-healthy promoting taxa (e.g., Bifidobacterium) and decrease harmful taxa (e.g., Bacteroides and Intestinibacter). Our findings also showed a significantly different abundance of gut microbiome taxa (e.g., Enterococcus faecium (i.e., E. faecium)) in T2D patients with poor compared to optimal glycemic control. Conclusions: This review provides evidence for glucose-lowering drug and gut microbiome interactions, highlighting the potential of gut microbiome modulators as co-adjuvants for T2D treatment

Skeletal maturation in relation to ethnic background in children of school age: The Generation R Study

Ethnicity is a well-established determinant of pediatric maturity, but the underlying genetic and environmental contributions to these ethnic differences are poorly comprehended. We aimed to evaluate the influence of ethnicity on skeletal age (SA), an assessment of pediatric maturation widely used in clinical settings. We included children from the Generation R Study, a multiethnic population-based pregnancy cohort, assessed at a mean age of 9.78 (±0.33) years. SA was evaluated by a trained observer on hand DXA scans using the Greulich and Pyle method. Ethnic background was defined as geographic ancestry (questionnaire-based assessment) (N = 5325) and genetic ancestry (based on admixture analysis) (N = 3413). Associations between the ethnic background and SA were investigated separately in boys and girls, using linear regression models adjusted for age, height and BMI. Based on geographic ancestry, 84% of the children were classified as European, 6% as Asian and 10% as African. Children of European background had on average younger SA than those of Asian or African descent. Asian boys had 0.46 (95% CI 0.26–0.66, p-value < 0.0001) and African boys 0.36 years (95% CI 0.20–0.53, p-value < 0.0001) older SA as compared to European boys. Similarly, Asian girls showed 0.64 (95% CI 0.51–0.77, p-value < 0.0001) and African girls 0.38 years (95% CI 0.27–0.48, p-value < 0.0001) older SA as compared to European girls. A similar pattern was observed in the analysis with genetically-defined ancestry. Furthermore, an increase in the proportion of Asian or African component was associated with older SA in both boys (log[Non-European/European]proportion = 0.10, 95% CI 0.06–0.13, p-value < 0.0001) and girls (log[Non-European/European]proportion = 0.06, 95% CI 0.04–0.08, p-value < 0.0001). In summary, children of Asian and African backgrounds have on average older SA as compared to children of European descent, partially explained by a genetic com

Bi-Directional Interactions between Glucose-Lowering Medications and Gut Microbiome in Patients with Type 2 Diabetes Mellitus: A Systematic Review

Background: Although common drugs for treating type 2 diabetes (T2D) are widely used, their therapeutic effects vary greatly. The interaction between the gut microbiome and glucose-lowering drugs is one of the main contributors to the variability in T2D progression and response to therapy. On the one hand, glucose-lowering drugs can alter gut microbiome components. On the other hand, specific gut microbiota can influence glycemic control as the therapeutic effects of these drugs. Therefore, this systematic review assesses the bi-directional relationships between common glucose-lowering drugs and gut microbiome profiles. Methods: A systematic search of Embase, Web of Science, PubMed, and Google Scholar databases was performed. Observational studies and randomised controlled trials (RCTs), published from inception to July 2023, comprising T2D patients and investigating bi-directional interactions between glucose-lowering drugs and gut microbiome, were included. Results: Summarised findings indicated that glucose-lowering drugs could increase metabolic-healthy promoting taxa (e.g., Bifidobacterium) and decrease harmful taxa (e.g., Bacteroides and Intestinibacter). Our findings also showed a significantly different abundance of gut microbiome taxa (e.g., Enterococcus faecium (i.e., E. faecium)) in T2D patients with poor compared to optimal glycemic control. Conclusions: This review provides evidence for glucose-lowering drug and gut microbiome interactions, highlighting the potential of gut microbiome modulators as co-adjuvants for T2D treatment

Identification of Transcripts with Shared Roles in the Pathogenesis of Postmenopausal Osteoporosis and Cardiovascular Disease

Epidemiological evidence suggests existing comorbidity between postmenopausal osteoporosis (OP) and cardiovascular disease (CVD), but identification of possible shared genes is lacking. The skeletal global transcriptomes were analyzed in trans-iliac bone biopsies (n = 84) from clinically well-characterized postmenopausal women (50 to 86 years) without clinical CVD using microchips and RNA sequencing. One thousand transcripts highly correlated with areal bone mineral density (aBMD) were further analyzed using bioinformatics, and common genes overlapping with CVD and associated biological mechanisms, pathways and functions were identified. Fifty genes (45 mRNAs, 5 miRNAs) were discovered with established roles in oxidative stress, inflammatory response, endothelial function, fibrosis, dyslipidemia and osteoblastogenesis/calcification. These pleiotropic genes with possible CVD comorbidity functions were also present in transcriptomes of microvascular endothelial cells and cardiomyocytes and were differentially expressed between healthy and osteoporotic women with fragility fractures. The results were supported by a genetic pleiotropy-informed conditional False Discovery Rate approach identifying any overlap in single nucleotide polymorphisms (SNPs) within several genes encoding aBMD- and CVD-associated transcripts. The study provides transcriptional and genomic evidence for genes of importance for both BMD regulation and CVD risk in a large collection of postmenopausal bone biopsies. Most of the transcripts identified in the CVD risk categories have no previously recognized roles in OP pathogenesis and provide novel avenues for exploring the mechanistic basis for the biological association between CVD and OP.</p

Identification of Transcripts with Shared Roles in the Pathogenesis of Postmenopausal Osteoporosis and Cardiovascular Disease

Epidemiological evidence suggests existing comorbidity between postmenopausal osteoporosis (OP) and cardiovascular disease (CVD), but identification of possible shared genes is lacking. The skeletal global transcriptomes were analyzed in trans-iliac bone biopsies (n = 84) from clinically well-characterized postmenopausal women (50 to 86 years) without clinical CVD using microchips and RNA sequencing. One thousand transcripts highly correlated with areal bone mineral density (aBMD) were further analyzed using bioinformatics, and common genes overlapping with CVD and associated biological mechanisms, pathways and functions were identified. Fifty genes (45 mRNAs, 5 miRNAs) were discovered with established roles in oxidative stress, inflammatory response, endothelial function, fibrosis, dyslipidemia and osteoblastogenesis/calcification. These pleiotropic genes with possible CVD comorbidity functions were also present in transcriptomes of microvascular endothelial cells and cardiomyocytes and were differentially expressed between healthy and osteoporotic women with fragility fractures. The results were supported by a genetic pleiotropy-informed conditional False Discovery Rate approach identifying any overlap in single nucleotide polymorphisms (SNPs) within several genes encoding aBMD- and CVD-associated transcripts. The study provides transcriptional and genomic evidence for genes of importance for both BMD regulation and CVD risk in a large collection of postmenopausal bone biopsies. Most of the transcripts identified in the CVD risk categories have no previously recognized roles in OP pathogenesis and provide novel avenues for exploring the mechanistic basis for the biological association between CVD and OP.</p

Fetal and childhood growth patterns associated with bone mass in school-age children: The generation R study

Low birth weight is associated with lower bone accrual in children and peak bone mass in adults. We assessed how different patterns of longitudinal fetal and early childhood growth influence bone properties at school age. In 5431 children participating in a population-based prospective cohort study, we measured fetal growth by ultrasound at 20 and 30 weeks gestation, and childhood growth at birth, 1, 2, 3, and 4 years of age. We analy

Genetic Evidence for a Causal Role of Serum Phosphate in Coronary Artery Calcification:The Rotterdam Study

BACKGROUND: Hyperphosphatemia has been associated with coronary artery calcification (CAC) mostly in chronic kidney dis-ease, but the association between phosphate levels within the normal phosphate range and CAC is unclear. Our objectives were to evaluate associations between phosphate levels and CAC among men and women from the general population and assess causality through Mendelian randomization. METHODS AND RESULTS: CAC, measured by electron-beam computed tomography, and serum phosphate levels were assessed in 1889 individuals from the RS (Rotterdam Study). Phenotypic associations were tested through linear models adjusted for age, body mass index, blood pressure, smoking, prevalent cardiovascular disease and diabetes, 25-hydroxyvitamin D, total calcium, C-reactive protein, glucose, and total cholesterol: high-density lipoprotein cholesterol ratio. Mendelian randomiza-tion was implemented through an allele score including 8 phosphate-related single-nucleotide polymorphisms. In phenotypic analyses, serum phosphate (per 1 SD) was associated with CAC with evidence for sex interaction (Pinteraction =0.003) (men β, 0.44 [95% CI, 0.30– 0.59]; P=3×10−9; n=878; women β, 0.24 [95% CI, 0.08– 0.40]; P=0.003; n=1011). Exclusion of hyperphos-phatemia, chronic kidney disease (estimated glomerular filtration rate &lt;60 mL/min per 1.73 m2) and prevalent cardiovascular disease yielded similar results. In Mendelian randomization analyses, instrumented phosphate was associated with CAC (total population β, 0.93 [95% CI: 0.07–1.79]; P=0.034; n=1693), even after exclusion of hyperphosphatemia, chronic kidney disease and prevalent cardiovascular disease (total population β, 1.23 [95% CI, 0.17– 2.28]; P=0.023; n=1224). CONCLUSIONS: Serum phosphate was associated with CAC in the general population with stronger effects in men. Mendelian randomization findings support a causal relation, also for serum phosphate and CAC in subjects without hyperphosphatemia, chronic kidney disease, and cardiovascular disease. Further research into underlying mechanisms of this association and sex differences is needed.</p

Ancestry and dental development: A geographic and genetic perspective

Objective: In this study, we investigated the influence of ancestry on dental development in the Generation R Study. Methods: Information on geographic ancestry was available in 3,600 children (1,810 boys and 1,790 girls, mean age 9.81±0.35 years) and information about genetic ancestry was available in 2,786 children (1,387 boys and 1,399 girls, mean age 9.82±0.34 years). Dental development was assessed in all children using the Demirjian method. The associations of geographic ancestry (Cape Verdean, Moroccan, Turkish, Dutch Antillean, Surinamese Creole and Surinamese Hindustani vs Dutch as the reference group) and genetic content of ancestry (European, African or Asian) with dental development was analyzed using linear regression models. Results: In a geographic perspective of ancestry, Moroccan (β=0.18; 95% CI: 0.07, 0.28), Turkish (β=0.22; 95% CI: 0.12, 0.32), Dutch Antillean (β=0.27; 95% CI: 0.12, 0.41), and Surinamese Creole (β=0.16; 95% CI: 0.03, 0.30) preceded Dutch children in dental development. Moreover, in a genetic perspective of ancestry, a higher proportion of European ancestry was associated with decelerated dental development (β=-0.32; 95% CI: -.44, -.20). In contrast, a higher proportion of African ancestry (β=0.29; 95% CI: 0.16, 0.43) and a higher proportion of Asian ancestry (β=0.28; 95% CI: 0.09, 0.48) were associated with accelerated dental development. When investigating only European children, these effect estimates increased to twice as large in absolute value. Conclusion: Based on a geographic and genetic perspective, differences in dental development exist in a population of heterogeneous ancestry and should be considered when describing the physiological growth in children