SALAMANDER: SALivAry bioMarkers of mediterraneAN Diet associated with long-tERm protection against type 2 diabetes mellitus

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.

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.

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