SALAMANDER: SALivAry bioMarkers of mediterraneAN Diet associated with long-tERm protection against type 2 diabetes mellitus
Lead Research Organisation:
King's College London
Department Name: Dental Institute
Abstract
Type 2 diabetes mellitus (T2DM) is a major public health concern, affecting more than 400 million adults worldwide, a figure that may rise to 642 million by 2040. Effective strategies to prevent or delay the onset of the disease include modifiable factors such as lifestyle, physical activity and nutrition. The Mediterranean Diet (MeDi) combines different food groups that are beneficial for nutrition-related diseases. A MeDi diet is characterized by high consumption of vegetables, legumes, fruits, cereals and olive oil, moderate-to-high intake of fish, low intake of dairy products and meat, and low-to-moderate intake of wine. Beyond dietary habits, the MeDi is also part of a lifestyle with traditional practices, skills and traditions. The MeDi has been consistently associated with a lower risk of T2DM over time in several studies. In this project, we aim at identifying salivary biomarkers of a healthy dietary pattern (MeDi) associated with prevention of T2M. In SALAMANDER, the main idea is that among healthy subjects, some salivary patterns may convey two types of information: adherence to MeDi and a future positive affect on health (protection against T2DM in the following 7 to 11 years).
The study will look at 3 groups of subjects across Europe: initially the UK Biobank, N= 85 000 and then two cohorts specifically of older adults: the ENRICA study in Spain and the 3-City study in Bordeaux France. Blood samples, questionnaires data (lifestyle including physical activity, diet, dietary supplements, clinical data and drug use...) and physical measurements (anthropometrics, blood pressure...) are available in the three cohorts. In addition, saliva samples have been taken at baseline on the UK Biobank. A detailed description of the cohorts is provided in part 3 of this application.
The study will look at 3 groups of subjects across Europe: initially the UK Biobank, N= 85 000 and then two cohorts specifically of older adults: the ENRICA study in Spain and the 3-City study in Bordeaux France. Blood samples, questionnaires data (lifestyle including physical activity, diet, dietary supplements, clinical data and drug use...) and physical measurements (anthropometrics, blood pressure...) are available in the three cohorts. In addition, saliva samples have been taken at baseline on the UK Biobank. A detailed description of the cohorts is provided in part 3 of this application.
Technical Summary
Saliva offers the advantages of simple and non-invasive sampling and a rich source of biomarkers thanks to the high diversity of its microbiome, proteome and metabolome. Recent results suggest that saliva composition in humans is dependent on diet quality and diversity. The main objective of the proposed project is to identify and validate salivary signatures indicative of healthy
dietary choices (adoption of a Mediterranean diet) with a positive long-term health outcome (protection against type 2 diabetes) throughout adult life.
Saliva samples and data on diet, lifestyle and health questionnaires will be obtained from UK Biobank, the largest salivary bank in Europe (85000 saliva donors) collected between 2006 and 2010. This will enable researchers to relate past salivary and dietary patterns to current health status. It is expected that approximately 3000 subjects from whom saliva was sampled will now have diabetes. For biomarker discovery, subjects will be categorized as follows: healthy at baseline, and either still healthy (H+) or currently diagnosed with type 2 diabetes (H-). Compliance to the Mediterranean diet (D+, D-) will also be evaluated with appropriate adjustment factors (physical activity, dietary supplements...). Within each of the four D/H groups, 50 subjects will be randomly selected and their salivary microbiome, proteome and metabolome will be analysed and data integrated to define a multimarker signature of healthy diet associated with protection against type 2 diabetes. The biomarker signature will be validated by examining two additional population-based cohorts of elderly subjects in Spain (ENRICA) and France (3City-Bordeaux), enabling verification of whether the identified biomarkers signatures are conserved as ageing proceeds. The project will advance nutritional epidemiology by proposing objective and non-invasive biomarkers of compliance to a beneficial diet associated with prevention of a diet-related disease.
dietary choices (adoption of a Mediterranean diet) with a positive long-term health outcome (protection against type 2 diabetes) throughout adult life.
Saliva samples and data on diet, lifestyle and health questionnaires will be obtained from UK Biobank, the largest salivary bank in Europe (85000 saliva donors) collected between 2006 and 2010. This will enable researchers to relate past salivary and dietary patterns to current health status. It is expected that approximately 3000 subjects from whom saliva was sampled will now have diabetes. For biomarker discovery, subjects will be categorized as follows: healthy at baseline, and either still healthy (H+) or currently diagnosed with type 2 diabetes (H-). Compliance to the Mediterranean diet (D+, D-) will also be evaluated with appropriate adjustment factors (physical activity, dietary supplements...). Within each of the four D/H groups, 50 subjects will be randomly selected and their salivary microbiome, proteome and metabolome will be analysed and data integrated to define a multimarker signature of healthy diet associated with protection against type 2 diabetes. The biomarker signature will be validated by examining two additional population-based cohorts of elderly subjects in Spain (ENRICA) and France (3City-Bordeaux), enabling verification of whether the identified biomarkers signatures are conserved as ageing proceeds. The project will advance nutritional epidemiology by proposing objective and non-invasive biomarkers of compliance to a beneficial diet associated with prevention of a diet-related disease.
Planned Impact
Impact summary
Publications
Shaalan AK
(2021)
Inhibition of Aurora Kinase B activity disrupts development and differentiation of salivary glands.
in Cell death discovery
Chambon C
(2021)
The salivary proteome reflects some traits of dietary habits in diabetic and non-diabetic older adults.
in European journal of nutrition
Shaalan A
(2022)
Alterations in the Oral Microbiome Associated With Diabetes, Overweight, and Dietary Components
in Frontiers in Nutrition
André P
(2020)
The role of overweight in the association between the Mediterranean diet and the risk of type 2 diabetes mellitus: a mediation analysis among 21 585 UK biobank participants.
in International journal of epidemiology
Proctor GB
(2021)
Disease-Induced Changes in Salivary Gland Function and the Composition of Saliva.
in Journal of dental research
Proctor G
(2017)
The SALAMANDER project: SALivAry bioMarkers of mediterraneAN Diet associated with long-tERm protection against type 2 diabetes
in Nutrition Bulletin
Description | The Medi (Mediterranean) Diet is substantially plant-based and widely percieved to be a healthier diet. 1. We obtained nutritional data of subjects who took part in the UK Biobank study and gave a numerical score to indicate degree of adherence to a Medi Diet. We found that increased adherence to the Medi Diet was associated with a lower risk of type 2 diabetes (T2DM) and this was due to a lower risk of being overweight and to a direct effect of the Medi Diet on development of T2DM, suggesting that the Medi Diet is also beneficial for those who are not overweight. This might be due to a higher consumption of important nutrients such as vitamins and antioxidants and a lesser consumption of saturated fats and refined sugars. These results have been published. 2. We collected saliva samples from 2 cohorts of elderly subjects (3C-Bordeaux, France and Seniors-ENRICA-2, Madrid) and analysed the proteins present. We found that specific proteins in saliva were helpful as markers of dietary intake of vegetables, butter and sweet snacks. These results have been submitted for publication. 3. Saliva samples from the Seniors-ENRICA-2 cohort of subjects were analysed to determine the composition of microrganisms (microbiome). We found that, in subjects with T2DM, the diversity of bacterial species was reduced and clusters of certain bacterial species were more abundant. We also found that clusters of certain bacterial species were associated with increased consumption of sugary snacks along with decreased consumption of fish/ shellfish and nuts. A manuscript describing these results is in preparation. |
Exploitation Route | These results are relevant for public health, in particular for encouraging a Mediterranean-like dietary pattern for primary prevention of type 2 diabetes mellitus and overweight/obesity. |
Sectors | Agriculture, Food and Drink,Healthcare |
URL | http://www.inra.fr/salamander |
Title | 16S amplicon sequencing data for saliva samples of diabetic patients |
Description | 16S amplicon sequencing data for saliva samples of elderly type-2 diabetic and non-diabetic patients stratified according to adherence to a mediterranean style diet |
Type Of Material | Database/Collection of data |
Year Produced | 2022 |
Provided To Others? | Yes |
Impact | It can be concluded that the microbial community structure of saliva is altered in T2DM and obesity and is associated with altered consumption of particular food items. In order to further substantiate these observations a prospective study should be undertaken to assess the impact of diets aimed at modifying diabetic status and reducing weight. |
URL | https://www.ebi.ac.uk/ena/browser/view/PRJEB51205 |
Title | 3Cités cohort saliva sample collection |
Description | A collection of saliva samples from a subgroup of patients in the 3Cités cohort of individuals aged 65 and over in Bordeaux, Dijon and Montpellier |
Type Of Material | Database/Collection of data |
Year Produced | 2018 |
Provided To Others? | No |
Impact | This saliva sample collection with associated data on the cohort is part of the revised SALAMANDER study |
URL | https://www6.inrae.fr/salamander/Consortium/UBx |
Title | ENRICA-Seniors cohort saliva sample collection |
Description | Saliva samples have been collected from subjects who are part of the ENRICA-Seniors cohort created by the Universidad Autónoma de Madrid. |
Type Of Material | Database/Collection of data |
Year Produced | 2018 |
Provided To Others? | No |
Impact | The creation of this saliva sample has enabled the objectives of the SALAMANDER study to be investigated. |
URL | https://www6.inrae.fr/salamander/Consortium |
Description | SALAMANDER project: SALivAry bioMarkers of mediterraneAN Diet associated with long-tERm protection against type 2 diabetes |
Organisation | Autonomous University of Madrid |
Country | Spain |
Sector | Academic/University |
PI Contribution | Analysis of the microbiome of saliva samples. |
Collaborator Contribution | Selection and collection of salivas from the ENRICA cohort |
Impact | Publication of paper |
Start Year | 2017 |
Description | SALAMANDER project: SALivAry bioMarkers of mediterraneAN Diet associated with long-tERm protection against type 2 diabetes |
Organisation | University of Bordeaux |
Country | France |
Sector | Academic/University |
PI Contribution | Analysis of salivary microbiome |
Collaborator Contribution | Collection of saliva samples from 3-C Bordeaux cohort |
Impact | Publication of paper. |
Start Year | 2017 |
Description | School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju, Republic of Korea |
Organisation | Gwangju Institute of Science and Technology |
Country | Korea, Republic of |
Sector | Academic/University |
PI Contribution | 16Srnagene sequencing of microbiome in saliva samples |
Collaborator Contribution | Bioinformatics analysis of sequences |
Impact | Manuscript in preparation, to be submitted in March/ April, 2022. Sequencing data to be uploaded to European Nucleotide Archive in March 2022. |
Start Year | 2021 |