Umeå University's logo

Background: Dietary choices are shaped by both genetic predisposition and environmental exposures, yet the relative influence of these factors remains insufficiently understood across populations and age groups. Young adulthood represents a critical period when long-term eating habits take form, and clarifying the determinants of dietary behavior in this life stage may inform strategies to promote sustained health.

Objectives: This twin study aimed to estimate genetic and environmental contributions to food, energy, and nutrient intakes, and taste preferences in young adults in Sweden.

Methods: The study included 2832 Swedish twins (858 monozygotic and 1974 dizygotic; mean age 24 y; 59.5% female). Participants completed a validated dietary questionnaire assessing food intake frequencies and taste preferences. Additive genetic (A), shared environmental (C), and nonshared environmental (E) influences on a priori dietary indices, specific food and nutrient intakes, and taste preferences were estimated using classical ACE twin models and nested models fitted in OpenMx.

Results: Heritability estimates across dietary traits ranged from 20% to 61%. Genetic influences on overall dietary pattern indices exceeded 40%. Heritability varied across food groups (e.g., 61% for venison; 24% for potatoes) and nutrient intakes (50% for fiber; 20% for sodium), indicating differing degrees of genetic impact across dietary components. Taste preferences also showed substantial genetic contributions (21%–61%), with the strongest effects observed for bitter foods (e.g., black coffee, grapefruit), followed by sweet foods (e.g., jam/marmalade).

Conclusions: This large-scale twin study provides a comprehensive overview of genetic and environmental influences on dietary behavior in young adults, showing substantial genetic and nonshared environmental contributions across diverse dietary traits. These results provide a foundation for future research on diet–disease relationships and may support the development of prevention and intervention strategies, including emerging precision-nutrition approaches.

Genome-Wide Association Studies (GWAS) are the primary method used to investigate the effects of common genetic variants on health and disease and are increasingly used as an arena for applied epidemiological methods. There are now a growing number of applications of GWAS in oral health research, yielding exciting findings and holding great potential for future discoveries. While exciting, the GWAS approach has inherent limitations, and the success of these experiments depends on achieving adequate statistical power. In the context of dental diseases, where multiple genetic variants have small effects, very large samples are needed to unlock the full potential of GWAS. This article discusses the motivation for undertaking these studies, introduces the GWAS method, and highlights the potential of GWAS to help unravel the complex factors influencing oral health and diseases. Alongside the promises of GWAS, this article also summarizes the key challenges that need to be addressed for this method to be deployed usefully and suggests criteria to consider during the appraisal of a GWAS paper.

Introduction: The global population is aging. Although aging populations experience a high burden of dental and systemic diseases, few studies have described the oral microbiota in aging population-based cohorts. This observational, registry-based study aimed to characterize the diversity and composition of the oral microbiota in 1,093 aging Swedes—aged 54–84 years at inclusion—and evaluate associations with host traits, as well as prospective measures of caries and periodontal status.

Methods: Saliva microbiota was characterized using complete 16S rRNA gene sequencing, and dental data were obtained from primary care dental records. Partial least squares regression was used to identify species associated with variation in age, number of teeth, total number of sequence reads, caries, and periodontal status. Follow-up analyses were conducted using two-part regression models with covariate adjustments.

Results: The oral microbiota remained highly diverse in the aging population without major shifts within this age frame. Carriage of hitherto unfamiliar yet well-documented disease-associated species was found to be associated with metrics of active disease but not lifelong measures, such as the common decayed, filled, and missing surfaces index.

Conclusion: These results underscore methodological considerations, including the importance of read number adjustments beyond using relative abundances, and the importance of carefully selecting metrics for oral disease in aging individuals.

Objectives: The objectives were to: (i) assess the accuracy of dental data for adults obtained from the Swedish Quality Register on Caries and Periodontitis (SKaPa); (ii) explore whether Latent Class Analysis (LCA) can identify groups of people based on caries data; and (iii) characterise the dental, medical and behavioural characteristics of people in the LCA-derived classes.

Methods: Caries data from the SKaPa register were compared with clinical data collected by five experienced dentists in a nested subgroup of the Malmö Offspring Study (MOS), namely the Malmö Offspring Dental Study (MODS) (n = 724) for validation. Dental data from SKaPa were then used to classify 61 984 adult participants of the Västerbotten Intervention Programme (VIP) into five classes using LCA and DMFS-based quintile ranking, respectively. Dental status (including caries progression over 5 years), medical, anthropometric and behavioural characteristics were compared between the groups. Analyses were replicated in 2767 adults in the MOS.

Results: DMFS-scores and number of teeth recorded within −2 to +2 years showed excellent agreement between the SKaPa and reference data with intra-class correlations > 0.90. The five LCA classes differed in mean DMFS from 10.0 to 94.4. There were strong associations between LCA class and health, and health and behavioural measures respectively, including some associations that were not detected using DMFS-ranked quintile groups. LCA class was associated with incremental change in DMFS, DFS, and number of teeth. The results in the MOS cohort were consistent with the results in the VIP cohort.

Conclusions: Dental data for adults from the SKaPa registry were considered accurate within 2 years of recording. The LCA approach can classify participants into caries subtypes based on dental charting. These groups differ in health and behavioural characteristics and future caries increment. The LCA approach may capture some information that is missing from DMFS-ranked quintile groups, but is also heavily influenced by total DMFS, meaning that applying LCA in cumulative, highly age-determined diseases, such as caries, is a challenge.

Introduction: Infant formulas with reduced iron levels and lactoferrin (Lf) supplementation might mimic the beneficial effects of breast milk on the oral microbiome. This study aimed to investigate the impact of a bovine Lf-supplemented and iron-reduced formula on the oral microbiota in infants at 4, 6 and 12 months.

Methods: In a double-blind controlled trial, 6-week-old formula-fed infants were randomized to receive either a formula with reduced iron levels (2 mg/L) and Lf supplementation (1 g/L) (n = 72), the same formula without Lf (n = 72), or a standard formula (8 mg iron/L) (n = 36). A breast-fed reference group (n = 72) was also included. The oral microbiota was analyzed at 4 (n = 244), 6 (n = 216) and 12 (n = 229) months of age using the Oxford Nanopore Technology of the 16S rRNA gene annotation (eHOMD database).

Results: Neither the within- or between-group diversities nor overall microbiota pattern assessment revealed any statistically significant differences in microbiota composition between the formula groups. However, single species were significantly associated with specific formula-fed groups. At 6 months, breast-fed infants exhibited significantly lower species richness and distinct microbiota composition compared to the formula-fed groups.

Conclusions: The effects of reduced iron levels and lactoferrin supplementation of infant formula on the oral microbiome were inconclusive.

Background/Objectives: Trimethylamine N-oxide (TMAO), a gut microbiota-derived metabolite from L-carnitine and choline (abundant in meat and eggs), is linked to CVD and T2D. This study investigated whether TMAO responses to animal-based foods differ between individuals with and without metabolic syndrome (MetS), in relation to their gut microbiota composition.

Subjects/Methods: In a randomized crossover trial, 12 MetS (≥3 criteria according to the Adult Treatment Panel III: elevated waist circumference, fasting glucose, triglycerides, and blood pressure or reduced HDL cholesterol) and 21 non-MetS subjects consumed two test meals (3 hard-boiled eggs or 170 g meat balls) after overnight fasting, with ≥1-week washout. Blood was collected at baseline and 0.5, 1, 2, 4, and 6 h postprandially; urine was collected over 6 h. Fecal samples (collected pre-first day of intervention) underwent 16S rRNA sequencing. Plasma and urinary TMAO, TMA, choline, and carnitine were quantified using UPLC-MS/MS.

Results: MetS subjects exhibited a non-significant trend towards higher incremental AUCs for plasma TMA, TMAO, choline, and carnitine after consuming both foods, with a 30–50% higher urinary TMAO excretion (but similar for TMA) versus non-MetS subjects. This exploratory analysis also indicated that MetS subjects had reduced gut microbial diversity, featuring decreased Blautia glucerasea (butyrate producer) and increased Ruminococcus torques (pro-inflammatory), a profile associated with inflammation but not TMA production.

Conclusion: No significant increase in plasma methylamines after choline and carnitine challenge was observed in subjects with MetS compared with non-MetS. In MetS subjects (without CVD and T2D), gut microbiota composition was characterized by increased pro-inflammatory bacteria rather than TMAO-generating bacteria. The lack of statistical significance with regard to plasma TMAO response could be due to an insufficient sample size rather than the absence of an effect. Nevertheless, the observed elevation might still be clinically relevant, supported by concurrent differences in microbiota composition. These preliminary findings warrant validation in larger cohorts due to sample size limitations.

Background/Objectives: Trimethylamine N-oxide (TMAO) is a gut microbiota-dependent metabolite considered as a risk metabolite for various non-communicable diseases. This study aims to identify differences in the gut microbiota composition and concentrations of TMAO and related metabolites in subjects with and without metabolic syndrome (MetS).

Methods: Plasma samples were collected following an overnight fast on two occasions from subjects with (n = 12) and without (n = 21) MetS. Feces samples were collected on the day before the first blood sampling. The gut microbiota was profiled using 16S rRNA full-gene amplification sequencing. TMAO and related methylamines were quantified using UPLC-MSMS. The fasted plasma glucose, plasma lipid profile, and HbA1c were determined, and blood pressure, circumference, height, and weight were measured.

Results: A divergent gut microbiota composition was observed in feces samples from both groups. In contrast to subjects without MetS, subjects with MetS had a reduced microbial diversity, with lower Blautia glucerasea and higher Ruminococcus torques-a pattern associated with (increased) inflammation. Trimethylamine (TMA)-producing bacteria were low in abundance across both groups. While plasma TMAO and related methylamines displayed no significant differences between both groups, L-carnitine was elevated (p = 0.0191) in subjects with MetS. A strong positive correlation was detected between TMAO and TMA (r = 0.439, p = 0.003), with a tendency to correlate with carnitine (r = 0.212, p = 0.087).

Conclusions: Subjects with MetS were characterized by gut microbiota favoring inflammation-associated species but not TMA producers. This suggests that TMAO may not play a role in MetS subjects without overt comorbidities, e.g., CVD or T2D. The influence of the gut microbiota on early MetS is likely mediated through inflammatory mechanisms driven by specific bacterial shifts rather than TMAO production.

Introduction: Periodontitis is associated with rheumatoid arthritis (RA). One hypothesis posits that this connection arises from the formation of autoantibodies against citrullinated proteins (ACPA) in inflamed gums, possibly triggered by Porphyromonas gingivalis. We previously demonstrated an increased antibody response to P. gingivalis arginine gingipains (anti-Rgp IgG), not only in individuals with severe periodontitis compared to controls, but in RA versus controls, with an association to ACPA. In the present study, we set out to further explore the relationship between anti-Rgp IgG, ACPA and periodontitis, including clinical periodontal parameters, in the large and well-characterized PerioGene North case-control study.

Methods: We measured serum levels of anti-Rgp and ACPA IgG by enzyme-linked immunosorbent assay (ELISA), in 478 patients with periodontitis and 509 periodontally healthy controls within PerioGene North. Subsequently, anti-Rgp IgG levels and ACPA status were analysed in relation to periodontitis and clinical periodontal parameters.

Results: Serum anti-Rgp IgG levels were elevated in cases versus controls (p< 0.001). However, receiver operating characteristic (ROC) curve analysis revealed that anti-Rgp IgG could not efficiently discriminate cases from controls (AUC= 0.63; 95% CI: 0.60 – 0.66). Among cases, increased anti-Rgp IgG levels associated with high periodontal inflammation and advanced alveolar bone loss (p<0.001 for both). An ACPA response was detected in 15 (3.1%) cases and 6 (1.2%) controls (p=0.033), but no association to periodontitis was evident after adjustment for age and smoking and anti-Rgp IgG levels did not differ between ACPA-positive and ACPA-negative individuals.

Conclusion: We show that anti-Rgp IgG identifies a subgroup of periodontitis patients with high degree of periodontal inflammation and advanced alveolar bone loss, but we do not find support for a link between periodontitis or anti-Rgp IgG and ACPA status in PerioGene North. Given the association between anti-Rgp and alveolar bone loss, the mechanistic role of gingipains in bone resorption should be experimentally explored.

Caries is a partially heritable disease, raising the possibility that a polygenic score (PS, a summary of an individual’s genetic propensity for disease) might be a useful tool for risk assessment. To date, PS for some diseases have shown clinical utility, although no PS for caries has been evaluated. The objective of the study was to test whether a PS for caries is associated with disease experience or increment in a cohort of Swedish adults. A genome-wide PS for caries was trained using the results of a published genome-wide association meta-analysis and constructed in an independent cohort of 15,460 Swedish adults. Electronic dental records from the Swedish Quality Registry for Caries and Periodontitis (SKaPa) were used to compute the decayed, missing, and filled tooth surfaces (DMFS) index and the number of remaining teeth. The performance of the PS was evaluated by testing the association between the PS and DMFS at a single dental examination, as well as between the PS and the rate of change in DMFS. Participants in the highest and lowest deciles of PS had a mean DMFS of 63.5 and 46.3, respectively. A regression analysis confirmed this association where a 1 standard deviation increase in PS was associated with approximately 4-unit higher DMFS (P < 2 × 10⁻¹⁶). Participants with the highest decile of PS also had greater change in DMFS during follow-up. Results were robust to sensitivity analysis, which adjusted for age, age squared, sex, and the first 20 genetic principal components. Mediation analysis suggested that tooth loss was a strong mediating factor in the association between PS and DMFS but also supported a direct genetic effect on caries. In this cohort, there are clinically meaningful differences in DMFS between participants with high and low PS for caries. The results highlight the potential role of genomic data in improving caries risk assessment.

Prolonged use of antibacterial mouthwash is linked to an increased risk of systemic disease. We aimed to investigate if disturbing the oral microbiota would impact the lower gut microbiome with functional effects in diet-induced obesity. Mice were exposed to oral chlorhexidine and fed a Western diet (WD). Food intake and weight gain were monitored, and metabolic function, blood pressure, and microbiota were analyzed. Chlorhexidine reduced the number of viable bacteria in the mouth and lowered species richness in the gut but with proportional enrichment of some bacteria linked to metabolic pathways. In mice fed a Western diet, chlorhexidine reduced weight gain, body fat, steatosis, and plasma insulin without changing caloric intake, while increasing colon triglycerides and proteins, suggesting reduced absorption of these nutrients. The mechanisms behind these effects as well as the link between the oral microbiome and small intestinal function need to be pinpointed. While the short-term effects of chlorhexidine in this model appear beneficial, potential long-term disruptions in the oral and gut microbiota and possible malabsorption should be considered.