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
SALAMANDER
2017-04-01
2020-03-31
Martine MORZEL
INRAE
France

Consortium

Partner Organization Partner Country
Université de BordeauxFrance
King's College LondonUnited Kingdom
Universidad Autonoma de MadridSpain

1. Overall project description


1.1 Summary

The SALAMANDER project aimed 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).


In a discovery phase, 214 subjects were selected in two cohorts of elderly people (3-C Bordeaux in France, Seniors-ENRICA in Spain) following a case-control design (cases: T2DM). Saliva samples were obtained and their microbiome, metabolome and proteome compositions were analyzed by 1H-NMR, 16SrRNA gene analyses and nano-LC MS/MS, respectively. This generated three datasets of 78 metabolites, 450 unique amplicon sequence variants and 246 proteins. Each dataset was first analyzed separately. There were differences in microbial diversity with some food groups defining MeDi. For example, subjects who ate more butter showed increased alpha diversity and differences in the presence of some genera including Prevotella, Porphyrmonas and Fusobacterium. Eating more vegetables resulted in a lower presence of Porphyrmonas, Peptostreptococcaceae and Saccharibacteria. For proteome, three food groups were explained by a model comprising proteins: eating vegetables (cohort + 5 proteins), butter (cohort + 4 proteins) and sweets & pastries (diabetic status, sex + 2 proteins).


The datasets of the discovery phase were also analyzed jointly. The microbiome and metabolome datasets shared much information: 60% of the variability in metabolome was explained by microbiome. In contrast, proteome was largely independent of microbiome (<10% of the variability in proteome explained by microbiome). Biomarkers of T2DM were sought in each cohort separately and in a meta-analysis : 5 proteins, ethanol and Coriobacteriia were significantly different between cases and controls. Interestingly, two of the proteins (Q96DA0, Q96DR5) were also significantly different between high and low consumers of butter. 


As a validation, 121 new Seniors-ENRICA participants were selected. 116 saliva samples were obtained and analyzed with the same methods as in the discovery phase for microbiome and proteome. Ethanol concentration was also measured. Overall, none of the T2DM biomarker candidates identified in the discovery phase (5 proteins, ethanol, Coriobacteriia) were confirmed. Only one protein was near significance both in the meta-analysis of the discovery phase and in the validation phase (gene CTBS).


The validation phase nonetheless provided interesting results. It first confirmed that variability in microbiome did not explain variability in proteome. Second, there were statistically significant differences in both alpha and beta diversities between participants who visit the dentist frequently (at least once a year) or not. This was particulary true for T2DM patients.


Overall, it was not possible to identify a signature of T2DM across both a discovery and a validation phase. However, the results strongly suggest that saliva reflects some aspects of usual diet.


1.2 Highlights

In view of identifying biomarkers of diet and health, we analyzed the microbiome, metabolome and proteome of saliva samples. Two key findings should be pointed out :


- Coordination between the three omics studied was evaluated. We found coordinated profiles of saliva microbiome and metabolome : how individuals are grouped is quite similar considering the profile of either saliva microbiome or metabolome. In contrast, saliva proteome has little information shared with the other two omics. This suggests that identification of biomarkers in saliva may benefit from the combined analysis of proteome on one hand and microbiome or metabolome on the other hand, since these two groups convey complementary information.


- The microbiome diversity and proteome composition were altered by the usual consumption of specific food groups such as vegetables or butter & cream. Although this should be confirmed, this opens the way of utilizing saliva (an easily accessible biofluid) as a source of objective markers of usual diet.


4. Impact


4.1 List of publications

AuthorsTitleYear, Issue, PPDoiPdf
Proctor GB, André P, Lopez-Garcia E , Gomez Cabrero Lopez D, Neyraud E, Feart C, Rodriguez Artalejo F, García García-Esquinas E & Morzel MThe SALAMANDER project: SALivAry bioMarkers of mediterraneAN Diet associated with long-tERm protection against type 2 diabetes.2017, 42: 369–37410.1111/nbu.12298
André P, Proctor G, Driollet B, Garcia-Esquinas E, Lopez-Garcia E, Gomez-Cabrero D, Neyraud E, Rodriguez-Artalejo F, Morzel M & Féart C.The role of overweight on the association between Mediterranean diet and risk of type 2 diabetes mellitus : a mediation analysis among 21 612 UK Biobank participants.accepted on 7th May 2020

4.2 Presentation of the project

Target groupAuthorsMeans of communicationHyperlinkPdf
Scientists (topic: nutrition)André P, Proctor GB, Rodriguez Artalejo F, Lopez-Garcia E, Gomez Cabrero Lopez D, García García-Esquinas E, Neyraud E, Morzel M & Féart C. 2017. Projet SALAMANDER : Biomarqueurs salivaires du régime méditerranéen associé à une protection à long terme contre le diabète de type 2. Journées Francophones de Nutrition, Nantes (FR) 13-15 December 2017.Poster
Scientists, medical doctorsAndré P, Proctor GB, Rodriguez Artalejo F, Lopez-Garcia E, Gomez Cabrero Lopez D, García García-Esquinas E, Neyraud E, Morzel M & Féart C. 2018. Projet SALAMANDER : Biomarqueurs salivaires du régime Méditerranéen associés à une protection au long terme contre le diabète de type 2. Congrès de la société Francophone du Diabète, Nantes (FR), 20-23 March 2018.e-poster
Scientists (topic: mass spectrometry)Bros 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 SFEAP (Société Française d’Electrophorèse et d’Analyse Protéomique), Albi (FR), 9-12 October 2018.Poster
Scientists, policy makersMorzel M. Salivary signatures of taste perception and diet. International Conference on Mediterranean Diet and Gastronomy, Evora (PT), 15-16 October 2018.oral communication (invited)
Scientists (topic: nutrition) Morzel M. Salivary bioMarkers of Mediterranean Diet associated with long-term protection against type 2 diabetes mellitus. Euro Nutrition 2018, Marne-la-Vallée (FR), 18-19 October 2018.oral communication (invited)
Scientists (topic: 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 (FR), 7-9 November 2018poster
Scientists (topic: 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, (FR), 28-30 November 2018.poster
Scientists, medical doctorsAndré P, Proctor G, Rodriguez-Artalejo F, Lopez-Garcia E, Gomez-Cabrero D, 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 la UK Biobank. Congrès de la Société Francophone du Diabète, Marseille (FR), 26-29 March 2019.oral communication
Scientists (topic: nutrition)Bros P, Di Biagio R, Sayd T, Neyraud E, Féart C, Proctor G, Rodriguez-Artalejo F, Lopez-Garcia E, Chambon C & Morzel M. Salivary protein markers of type 2 diabetes mellitus in elderly subjects and links with dietary habits. 5th International Congress of Translational Research in Human Nutrition., Clermont-Ferrand (FR), 20-21 June 2019.oral communication
Scientists (topic: nutrition)André P, Proctor G, Rodriguez-Artalejo F, Lopez-Garcia E, Gomez-Cabrero D, Neyraud E, Garcia-Esquinas E, Morzel M & Féart C. Mediation analysis to understand the role of overweight on the relationship between Mediterranean diet and risk of type 2 diabetes mellitus: evidence from 21612 UK Biobank participants. 5th International Congress of Translational Research in Human Nutrition., Clermont-Ferrand (FR), 20-21 June 2019.oral communication

4.3 List of submitted patents and other outputs

Patent licencePartners involvedYearInternational eu or national patentCommentPdf

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