A Cohort Study Followed for 13 Years

Background There is growing evidence of an association between oral health, specifically dental status, and chronic systemic diseases. However, varying measures of dental status across different populations and low study sample has made comparison of studies and conclusion of findings unclear. Our aim is to examine whether the number of teeth as a measure of dental status is associated with incident chronic diseases in a cohort setting. Methods We conducted a cohort study among 24,313 middle-aged Germans followed up for 13 years. Data on number of teeth as a measure of dental status were obtained through self-reports. Outcomes were clinically–verified incident non–fatal myocardial infarction, stroke, type 2 diabetes mellitus, and cancer. Hazard ratio (HR) and 95% confidence intervals (CI) were obtained from Cox regression models. Results Increasing number of teeth is inversely related to risk of myocardial infarction (HR: 0.97; 95% CI: 0.96, 0.99). The full multivariate model of teeth groups showed a strong linear trend for myocardial infarction, a less strong trend for stroke, and no relation with type 2 diabetes mellitus and cancer in a competing risk model. Participants with 18–23 teeth and those without teeth were at 76% (95%CI: 1.04, 3) and 2.93 times (95%CI: 1.61, 5.18) higher risk of myocardial infarction compared to those with nearly all teeth (28–32 teeth). Conclusions Number of teeth is specifically associated with myocardial infarction and not with other chronic disease indicating that dental status further strengthens the link between oral health and cardiovascular diseases

An investigation into the temporal reproducibility of Tryptophan metabolite networks among healthy adolescents

Tryptophan and its bioactive metabolites are associated with health conditions such as systemic inflammation, cardiometabolic diseases, and neurodegenerative disorders. There are dynamic interactions among metabolites of tryptophan. The interactions between metabolites, particularly those that are strong and temporally reproducible could be of pathophysiological relevance. Using a targeted metabolomics approach, the concentration levels of tryptophan and 18 of its metabolites across multiple pathways was quantified in 24-hours urine samples at 2 time-points, age 17 years (baseline) and 18 years (follow-up) from 132 (52% female) apparently healthy adolescent participants of the DOrtmund Nutritional and Anthropometric Longitudinally Designed (DONALD) Study. In sex-specific analyses, we applied 2 network approaches, the Gaussian graphical model and Bayesian network to (1) explore the network structure for both time-points, (2) retrieve strongly related metabolites, and (3) determine whether the strongly related metabolites were temporally reproducible. Independent of selected covariates, the 2 network approaches revealed 5 associations that were strong and temporally reproducible. These were novel relationships, between kynurenic acid and indole-3-acetic acid in females and between kynurenic acid and xanthurenic acid in males, as well as known relationships between kynurenine and 3-hydroxykynurenine, and between 3-hydroxykynurenine and 3-hydroxyanthranilic acid in females and between tryptophan and kynurenine in males. Overall, this epidemiological study using network-based approaches shed new light into tryptophan metabolism, particularly the interaction of host and microbial metabolites. The 5 observed relationships suggested the existence of a temporally stable pattern of tryptophan and 6 metabolites in healthy adolescent, which could be further investigated in search of fingerprints of specific physiological states. The metabolites in these relationships may represent a multi-biomarker panel that could be informative for health outcome

Blood Metabolomic Profiling Confirms and Identifies Biomarkers of Food Intake

Metabolomics can be a tool to identify dietary biomarkers. However, reported food-metabolite associations have been inconsistent, and there is a need to explore further associations. Our aims were to confirm previously reported food-metabolite associations and to identify novel food-metabolite associations. We conducted a cross-sectional analysis of data from 849 participants (57% men) of the PopGen cohort. Dietary intake was obtained using FFQ and serum metabolites were profiled by an untargeted metabolomics approach. We conducted a systematic literature search to identify previously reported food-metabolite associations and analyzed these associations using linear regression. To identify potential novel food-metabolite associations, datasets were split into training and test datasets and linear regression models were fitted to the training datasets. Significant food-metabolite associations were evaluated in the test datasets. Models were adjusted for covariates. In the literature, we identified 82 food-metabolite associations. Of these, 44 associations were testable in our data and confirmed associations of coffee with 12 metabolites, of fish with five, of chocolate with two, of alcohol with four, and of butter, poultry and wine with one metabolite each. We did not identify novel food-metabolite associations; however, some associations were sex-specific. Potential use of some metabolites as biomarkers should consider sex differences in metabolism

Dietary patterns are associated with serum metabolite patterns and their association Is influenced by gut bacteria among older German adults

Background: Although dietary intakes and dietary intake patterns (DPs) have been associated with single metabolites, it is unclear whether DPs are also reflected in specific metabolite patterns (MPs). Moreover, the influence of groups of gut bacteria on the relationship between DPs and MPs is underexplored. Objectives: We aimed to investigate the association of DPs and serum MPs and also the modifying effect of the gut bacteria compositional patterns (BCPs). Methods: This is a cross-sectional investigation among 225 individuals (median age: 63 y; 53% women) from the European Prospective Investigation into Cancer and Nutrition study. Dietary intakes were assessed by three 24-h dietary recalls, gut bacteria composition was quantified by 16S rRNA gene sequencing, and the serum metabolome was profiled by an untargeted approach. We identified DPs and BCPs by the treelet transform analysis. We modeled associations between DPs and 8 previously published MPs and the modifying effect of BCPs by fitting generalized linear models using DataSHIELD R. Results: We identified 5 DPs and 7 BCPs. The “bread, margarine, and processed meat” and “fruiting vegetables and vegetable oils” DPs were positively associated with the “amino acids” (β = 0.35; 95% CI: 0.02, 0.69; P = 0.03) and “fatty acids” MPs (β = 0.45; 95% CI: 0.16, 0.74; P = 0.01), respectively. The “tea and miscellaneous” was inversely associated with the “amino acids” (β = −0.28; 95% CI: −0.52, −0.05; P = 0.02) and “amino acid derivatives” MPs (β = −0.21; 95% CI: −0.39, −0.02; P = 0.03). One BCP negatively modified the association between the “bread, margarine, and processed meat” DP and the “amino acids” MP (P-interaction = 0.01). Conclusions: In older German adults, DPs are reflected in MPs, and the gut bacteria attenuate 1 DP–MP association. These MPs should be explored as biomarkers of these jointly consumed foods while taking into account a potentially modifying role of the gut bacteria

An investigation into the relationship of circulating gut microbiome molecules and inflammatory markers with the risk of incident dementia in later life

The gut microbiome may be involved in the occurrence of dementia primarily through the molecular mechanisms of producing bioactive molecules and promoting inflammation. Epidemiological evidence linking gut microbiome molecules and inflammatory markers to dementia risk has been mixed, and the intricate interplay between these groups of biomarkers suggests that their joint investigation in the context of dementia is warranted. We aimed to simultaneously investigate the association of circulating levels of selected gut microbiome molecules and inflammatory markers with dementia risk. This case-cohort epidemiological study included 805 individuals (83 years, 66% women) free of dementia at baseline. Plasma levels of 19 selected gut microbiome molecules comprising lipopolysaccharide, short-chain fatty acids, and indole-containing tryptophan metabolites as well as four inflammatory markers measured at baseline were linked to incident all-cause (ACD) and Alzheimer's disease dementia (AD) in binary outcomes and time-to-dementia analyses. Independent of several covariates, seven gut microbiome molecules, 5-hydroxyindole-3-acetic acid, indole-3-butyric acid, indole-3-acryloylglycine, indole-3-lactic acid, indole-3-acetic acid methyl ester, isobutyric acid, and 2-methylbutyric acid, but no inflammatory markers discriminated incident dementia cases from non-cases. Furthermore, 5-hydroxyindole-3-acetic acid (hazard ratio: 0.58; 0.36-0.94, P = 0.025) was associated with time-to-ACD. These molecules underpin gut microbiome-host interactions in the development of dementia and they may be crucial in its prevention and intervention strategies. Future larger epidemiological studies are needed to confirm our findings, specifically in exploring the repeatedly measured circulating levels of these molecules and investigating their causal relationship with dementia ris

Identification and Characterization of Human Observational Studies in Nutritional Epidemiology on Gut Microbiomics for Joint Data Analysis

In any research field, data access and data integration are major challenges that even large, well-established consortia face. Although data sharing initiatives are increasing, joint data analyses on nutrition and microbiomics in health and disease are still scarce. We aimed to identify observational studies with data on nutrition and gut microbiome composition from the Intestinal Microbiomics (INTIMIC) Knowledge Platform following the findable, accessible, interoperable, and reusable (FAIR) principles. An adapted template from the European Nutritional Phenotype Assessment and Data Sharing Initiative (ENPADASI) consortium was used to collect microbiome-specific information and other related factors. In total, 23 studies (17 longitudinal and 6 cross-sectional) were identified from Italy (7), Germany (6), Netherlands (3), Spain (2), Belgium (1), and France (1) or multiple countries (3). Of these, 21 studies collected information on both dietary intake (24 h dietary recall, food frequency questionnaire (FFQ), or Food Records) and gut microbiome. All studies collected stool samples. The most often used sequencing platform was Illumina MiSeq, and the preferred hypervariable regions of the 16S rRNA gene were V3-V4 or V4. The combination of datasets will allow for sufficiently powered investigations to increase the knowledge and understanding of the relationship between food and gut microbiome in health and disease

Zahnstatus und das Risiko für chronisch systemische Erkrankungen : die Rolle systemischer Inflammation, Autoimmunität und oraler Mikrobiota

Dental diseases leading to tooth loss have severe impact on normal functional capacity in biting, chewing, smiling, speaking, and psychosocial wellbeing, and as if these were not enough, these dental conditions have also been linked to chronic systemic diseases thereby affecting general health. To achieve a better understanding of the role of dentition status on chronic systemic diseases, there is a need to investigate the potential link between these conditions in a well-characterised population and also to investigate possible biological mechanisms that might elucidate disease pathogenesis. Additionally, the identification of poor dentition status and related biomarker of pathogenesis could help to detect individuals at high-risk of some chronic systemic diseases. Therefore, the present thesis investigated the relation between dentition status as measured by the number of teeth and chronic systemic diseases and the role of some possible biological mechanisms within the EPIC-Potsdam cohort. Lower numbers of teeth were largely associated with a higher risk myocardial infarction and to some extent with stroke. Decreasing number of teeth was not associated with elevated levels of hsCRP, a marker of low-grade inflammation. However, we observed a relationship between increasing quantity of an important periodontal pathogen, Porphyromonas gingivalis in the saliva and elevated levels of ACPA in the presence of high hsCRP. Further, we demonstrated that in the presence of an overall low bacterial diversity, high saliva periodontitis-associated bacteria and caries-associated bacteria were also associated with a reduced number of teeth. These bacteria were also important predictors of the number of teeth and hsCRP among individuals with low bacterial diversity. Collectively, these findings based on epidemiological observations indicate that tooth loss may be an additional risk factor for CVD. Low-grade inflammation, autoimmunity and the less diverse polybacterial oral community appear to play important roles. The quality of our studies and data, the strength of association, and consistency of results are remarkable. However, these findings need to be investigated further in other German populations. Additional evidence will strengthen potential public health actions.Zahnerkrankungen, die zu Zahnverlust führen, haben starke Auswirkungen auf die normale Funktionsfähigkeit hinsichtlich des Beißens, Kauens, Lächelns, Sprechens und psychosozialen Wohlbefindens. Außerdem konnte der Zustand der Zähne mit chronischen systemischen Erkrankungen verbunden werden, welche den allgemeinen Gesundheitszustand beeinflussen. Um ein besseres Verständnis zur Rolle des Zahnstatus auf chronische systemische Erkrankungen zu erhalten, sollte die mögliche Verbindung dieser Konditionen in einer gut beschriebenen Population erforscht werden und mögliche biologische Mechanismen untersucht werden, die die Pathogenese der Erkrankung verdeutlichen. Zusätzlich könnte die Identifizierung des schlechten Zahnstatus sowie krankheitsspezifischer Biomarker dazu beitragen, Individuen mit hohem Risiko für chronische systemische Erkrankungen zu ermitteln. Daher untersuchte die hier vorliegende Doktorarbeit die Verbindung zwischen dem Zustand der Zähne, gemessen an der Anzahl der Zähne, und den chronischen, systemischen Erkrankungen innerhalb der EPIC-Potsdam Kohorte. Sie geht außerdem auf die Rolle möglicher biologischer Mechanismen ein. Eine niedrige Anzahl an Zähnen wurde weitgehend mit einem höheren Risiko für Herzinfarkt oder auch Schlaganfall in Verbindung gebracht. Sie konnte nicht mit einem erhöhten hsCRP-Wert assoziiert werden, einem Marker für leichte Entzündungen. Wir beobachteten einen Zusammenhang zwischen zunehmenden Mengen des wichtigen periodontalen Bakterien, Porphyromonas gingivalis im Speichel und erhöhtem ACPA-Werten im Umfeld hoher hsCRP-Wert. Weiterhin konnten wir zeigen, dass im Kontext insgesamt niedriger bakterieller Vielfalt hohe Parodontitis -assoziierte Bakterien und karies-assoziierte Bakterien auch mit der niedrigen Anzahl an Zähnen in Verbindung gebracht werden können. Diese Bakterien waren auch wichtige Prediktoren für die Anzahl der Zähne und hsCRP bei Individuen mit niedriger bakterieller Vielfalt. Zusammengefasst zeigen diese drei auf epidemiologischen Beobachtungen basierenden Ergebnisse, dass Zahnverlust ein zusätzlicher Risikofaktor für Herz-Kreislauf-Erkrankungen sein könnte. Leichte Entzündung, Autoimmunität und eine weniger artenreiche orale Bakteriengemeinschaft scheinen eine wichtige Rolle zu spielen. Die Qualität unserer Studie und unserer Daten, die Stärke der Assoziation und die Konsistenz der Ergebnisse sind bemerkenswert. Schließlich sollten diese Ergebnisse weiter in anderen deutschen Populationen untersucht werden. Zusätzliche Untersuchungen könnten die öffentliche Gesundheit stärken.EC/FP7/290246/EU/Rheumatoid Arthritis and the Periodontal Inflammatory Disease/RAPI

Association between Number of Teeth and Chronic Systemic Diseases: A Cohort Study Followed for 13 Years

BACKGROUND: There is growing evidence of an association between oral health, specifically dental status, and chronic systemic diseases. However, varying measures of dental status across different populations and low study sample has made comparison of studies and conclusion of findings unclear. Our aim is to examine whether the number of teeth as a measure of dental status is associated with incident chronic diseases in a cohort setting. METHODS: We conducted a cohort study among 24,313 middle-aged Germans followed up for 13 years. Data on number of teeth as a measure of dental status were obtained through self-reports. Outcomes were clinically-verified incident non-fatal myocardial infarction, stroke, type 2 diabetes mellitus, and cancer. Hazard ratio (HR) and 95% confidence intervals (CI) were obtained from Cox regression models. RESULTS: Increasing number of teeth is inversely related to risk of myocardial infarction (HR: 0.97; 95% CI: 0.96, 0.99). The full multivariate model of teeth groups showed a strong linear trend for myocardial infarction, a less strong trend for stroke, and no relation with type 2 diabetes mellitus and cancer in a competing risk model. Participants with 18-23 teeth and those without teeth were at 76% (95%CI: 1.04, 3) and 2.93 times (95%CI: 1.61, 5.18) higher risk of myocardial infarction compared to those with nearly all teeth (28-32 teeth). CONCLUSIONS: Number of teeth is specifically associated with myocardial infarction and not with other chronic disease indicating that dental status further strengthens the link between oral health and cardiovascular diseases