SALivAry biomarkers of MediterraneAN Diet associated with long-tERm protection against type 2 diabetes mellitus

ERA-HDHL cofunded call “Biomarkers for Nutrition and Health” (BioNH 2016)
SALivAry biomarkers of MediterraneAN Diet associated with long-tERm protection against type 2 diabetes mellitus
Martine MORZEL


Partner Organization Partner Country

1. Overall project description

1.1 Summary

Saliva sampling is simple and non-invasive and this fluid is a rich source of biomarkers thanks to the high diversity of its microbiome, proteome and metabolome. The SALAMANDER project aims at defining salivary signatures indicative of healthy dietary choices (adherence to a Mediterranean diet: MeDi) with a positive long-term health outcome (protection against type 2 diabetes: T2DM).

We first described the link between adherence to MeDi and incidence of T2DM in the UK population. Our main hypothesis was that the benefit of MeDi on the reduced risk for T2DM was partly explained by an impact on weight status. We used nutritional and clinical data from 21612 UK Biobank participants. A nutritional score reflecting the adherence of each participant to a MeDi was computed. Then we identified participants with incident T2DM. Using regression-based mediation analyses, we observed that higher adherence to a MeDi was associated with a significant 14% reduced risk for diabetes (HR 0.86, 95%CI [0.83 – 0.90]) and that this effect was in part explained by an indirect effect mediated by a lower odds (-10%) of being overweight (HR 0.90, 95%CI [0.88 – 0.92]). 4% of the total effect were not explained by overweight (HR 0.96, 95%CI [0.93 – 0.99]). These results add a mechanistic explanation to the well-known association between a healthy dietary pattern and the lower risk of diabetes, and suggest that both overweight and non-overweight people should adopt a healthy dietary pattern to avoid T2DM.

In parallel, 200 saliva samples from older participants (cohorts 3 City-Bordeaux, France and ENRICA-Seniors, Spain) were obtained and analyzed by 16SrDNA analyses (microbiome), 1H NMR (metabolome) and LC-MS-MS (proteome). For microbiome, there were 25 abundant bacterial genera containing at least 0.5% of the total sequence reads. These were characteristic of oral microbial communities, the most abundant genera being Streptococcus, Veillonella, Prevotella and Neisseria. 450 unique amplicon sequence variants (ASVs) were identified. Alterations in the alpha and beta diversities of the oral microbiome was linked with age, sex and cohort but not with T2DM. Three dietary items (cooking with olive oil, butter and vegetables intake) were correlated with altered microbial diversity. For metabolome, 126 different peaks corresponding to 47 identified and 31 currently unidentified metabolites were quantified. In accordance with microbiome data, no robust model could explain the diabetic status by metabolome. Finally for proteome, 246 proteins were semi-quantified. Approximately 50 proteins were significantly different between diabetic and non-diabetic subjects. These proteins were linked to three dietary items: cooking with olive oil, butter and vegetables intake. 

The three datasets (microbiome, metabolome, proteome) are currently jointly analyzed in order to identify salivary markers of T2DM and/or dietary habits.

1.2 Highlights


4. Impact

4.1 List of publications

AuthorsTitleYear, Issue, PPPartners NumberDoiPdf
Lana A, Struijk EA, Arias-Fernandez L, Graciani A, Mesas AE, Rodriguez-Artalejo F, Lopez-Garcia E. Habitual Meat Consumption and Changes in Sleep Duration and Quality in Older Adults
Ortolá R, García-Esquinas E, García-Varela G, Struijk EA, Rodríguez-Artalejo F, Lopez-Garcia EInfluence of changes in diet quality on unhealthy aging: the Seniors-ENRICA cohort10.1016/j.amjmed.2019.03.023
Seniors-ENRICA cohort. Am J Med. 2019. doi: 10.1016/j.amjmed.2019.03.023. Machado-Fragua MD, Struijk EA, Ballesteros JM, Ortolá R, Rodriguez-Artalejo F, Lopez-Garcia E Habitual coffee consumption and risk of falls in 2 European cohorts of older adults.10.1093/ajcn/nqy369
Ballesteros JM, Struijk EA, Rodríguez-Artalejo F, López-García EMediterranean diet and risk of falling in community-dwelling older adults10.1016/j.clnu.2019.02.004
García-Esquinas E, Ortolá R, Prina M, Stefler D, Rodríguez-Artalejo F, Pastor-Barriuso RTrajectories of Accumulation of Health Deficits in Older Adults: Are There Variations According to Health Domains?10.1016/j.jamda.2018.12.023
Laclaustra M, Rodriguez-Artalejo F, Guallar-Castillon P, Banegas JR, Graciani A, Garcia-Esquinas E, Lopez-Garcia EThe inflammatory potential of diet is related to incident frailty and slow walking in older adults10.1016/j.clnu.2019.01.013
Martinez-Gomez D, Esteban-Cornejo I, Lopez-Garcia E, García-Esquinas E, Sadarangani KP, Veiga OL, Rodriguez-Artalejo FPhysical activity less than the recommended amount may prevent the onset of major biological risk factors for cardiovascular disease: a cohort study of 198 919 adults10.1136/bjsports-2018-099740
Sandoval-Insausti H, Pérez-Tasigchana RF, López-García E, Banegas JR, Rodríguez-Artalejo F, Guallar-Castillón PProtein Intake and Risk of Falls: A Prospective Analysis in Older Adults
Ortolá R, García-Esquinas E, Soler-Vila H, Ordovas JM, López-García E, Rodríguez-Artalejo FChanges in health status predict changes in alcohol consumption in older adults: the Seniors-ENRICA cohort123-129
Ortolá R, García-Esquinas E, López-García E, León-Muñoz LM, Banegas JR, Rodríguez-Artalejo FAlcohol consumption and all-cause mortality in older adults in Spain: an analysis accounting for the main methodological issues
Balboa-Castillo T, Struijk EA, Lopez-Garcia E, Banegas JR, Rodríguez-Artalejo F, Guallar-Castillon PLow vitamin intake is associated with risk of frailty in older adults
Laclaustra M, Rodriguez-Artalejo F, Guallar-Castillon P, Banegas JR, Graciani A, Garcia-Esquinas E, Ordovas J, Lopez-Garcia EProspective association between added sugars and frailty in older adults
Machado-Fragua MD, Struijk EA, Graciani A, Guallar-Castillon P, Rodríguez-Artalejo F, Lopez-Garcia ECoffee consumption and risk of physical function impairment, frailty and disability in older adults10.1007/s00394-018-1664-7

4.2 Presentation of the project

Target groupAuthorsMeans of communicationHyperlinkPdf
scientistsBros P, Sayd T, Neyraud E, Féart C, Proctor G, Rodriguez-Artalejo F, Hébraud M, Morzel M & Chambon C. Optimization of saliva sample preparation and analysis for identification of protein biomarkers. Congrès de la Société Française d’Electrophorèse et d’Analyse Protéomique, Albi, 9-12 October 2018.poster
scientists, policy makersMorzel M. Salivary signatures of taste perception and diet. International Conference on Mediterranean and Gastronomy, Evora, Portugal, 15-16 October 2018.oral communication (invited)
scientists, nutritionists Morzel M. Salivary bioMarkers of Mediterranean Diet associated with long-term protection against type 2 diabetes mellitus. Euro Nutrition 2018, Marne-la-Vallée, France, 18-19 October 2018.oral communication (invited)
scientists (nutrition)André P, Proctor G, Rodriguez-Artalejo F, Lopez-Garcia E, Gomez-Cabrero D, Neyraud E, Bros P, Garcia-Esquinas E, Morzel M & Féart C. Adherence to a Mediterranean diet, body mass index and risk of Type 2 Diabetes Mellitus: Results from the UK Biobank. EGEA VII conference, Lyon, France, 7-9 November 2018.poster
scientists (nutrition)André P, Proctor G, Rodriguez-Artalejo F, Lopez-Garcia E, Gomez-Cabrero D, Bros P, Neyraud E, Garcia-Esquinas E, Morzel M & Féart C. Adhérence au régime Méditerranéen, indice de masse corporelle et risque de diabète de type 2 : Résultats de l’étude UKBiobank. Journées Francophones de Nutrition, Nice, France, 28-30 Novembre 2018poster

4.3 List of submitted patents and other outputs

Patent licencePartners involvedYearInternational eu or national patentCommentPdf


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