Metabolic HEALTH through nutrition, microbiota, and tryptophan bioMARKers

ERA-HDHL cofunded call “Biomarkers for Nutrition and Health” (BioNH 2016)
Metabolic HEALTH through nutrition, microbiota, and tryptophan bioMARKers
Prof Ute Nöthlings
University of Bonn


Partner Organization Partner Country
German Center for Neurodegenerative DiseasesGermany
University College CorkIreland
Institut National de la Recherche AgronomiqueFrance
Fondazione Edmund Mach, Research and Innovation CentreItaly

1. Overall project description

1.1 Summary

HEALTHMARK comprises five partners, each leading one WP. The WP1 (University of Bonn, UB) aims to identify trajectories of anthropometry from childhood to young adulthood, their relation to cardiometabolic risk markers, urine-derived biomarkers, and faecal bacterial composition, and how the trajectories modify the relation between diet and these biomarkers. UB identified four and three body mass index (BMI) trajectory groups in boys and girls, respectively. The BMI trajectory was associated with high-density lipoprotein-cholesterol and interleukin(IL)-18 in boys, and diastolic blood pressure and IL-6 in girls. Boys following the ‘overweight’ trajectory had significantly higher IL-18 when compared to their ‘low-normal weight’ counterparts. UB also identified some putative urine biomarkers of age, gender, and BMI to be further investigated. The WP2 (German Center of Neurodegenerative Diseases, DZNE) aims to identify and stratify subgroups of metabolic health in the adult population by analysing to which extent the proportion of MRI- measured visceral adipose tissue is indicative of or yields additional health status information beyond metabolic health status as defined by standard criteria. For that, DZNE has developed novel methods to automatically segment body fat distribution from MRI recording. DZNE also aims to identify and stratify subgroups of metabolic health in the adult population. In collaboration with WP5 (Fondazione Edmund Mach, FEM), DZNE is working on identifying putative dietary biomarkers of tryptophan metabolism that classify those subgroups of metabolic health. The WP3 (Institut National de la Recherche Agronomique, INRA) aims to investigate the relationship of gut microbiota and tryptophan metabolism with metabolic health in obesity and the effect of this relationship on metabolic improvement following surgery-induced weight loss. Plasma levels of tryptophan and other amino acids and respective metabolites were measured for a preliminary assessment of the putative biomarkers of metabolic health before and after the surgery-induced weight loss. The WP4 (University College Cork/Teagasc, UCC/Teagasc) conducted a clinical investigation on the efficacy of the patented probiotic Lactobacillus mucosae DPC6426 as nutritional agent to modulate tryptophan metabolism and metabolic biomarkers. Preliminary results revealed an increased Lactobacillus count in stool samples in mildly hypercholesterolaemic adults, but no effect on total blood cholesterol or microbial diversity. The WP5 (FEM) aims to perform metabolomic profiling of biosamples. To this end, 672 urine samples from the DOrtmund Nutritional and Anthropometric Longitudinally Designed study; 104 plasma samples from Obesity study, and 150 plus 850 plasma samples from the Rhineland study have been profiled. FEM also built an in-house spectral library for structural elucidation and comparison of metabolites from these samples.

1.2 Highlights

HEALTHMARK investigates the complex associations between diet, microbiota, tryptophan metabolites of microbial metabolism, and metabolic health in a set-up of identification, replication, and validation of associations. The projects are organized in five work packages (WP), and overall all WPs are progressing adequately to achieve the HEALTHMARK objectives. HEALTHMARK identified trajectory of body mass index and its relation to cardiometabolic risk markers, developed novel methods to automatically segment body fat distribution from MRI recording, observed an impact of probiotic Lactobacillus mucosae DPC6426 on faecal Lactobacillus of mildly hypercholesterolaemic adults; and conducted untargeted metabolomic profiling and targeted profiling of tryptophan and other amino acids of biosamples. Indeed, HEALTHMARK is on its way to derive novel biomarker signatures which can be modulated by diet and which may aid in monitoring key biological processes on the trajectory to metabolically driven diseases. The set-up of identification, replication and validation will give rise to strong research findings in the area of microbiota-derived bioactive and metabolic health.

4. Impact

4.1 List of publications

AuthorsTitleYear, Issue, PPPartners NumberDoiPdf

4.2 Presentation of the project

Target groupAuthorsMeans of communicationHyperlinkPdf
Scientists, publicDinan TG. “Brain-gutmicrobiota axis: Implications for psychopathology”. Journée de la recherche translationnelle, Institut Pasteur, Paris, March 2018Presentation
ScientistsSchellekens H. “Bugs to Drugs: Gut bacteriaderived metabolites as major modulators of neuroendocrine systems within the gut-brain axis”. APC Forum, Cork, Ireland, March 2018.Presentation
ScientistsOrozco-Ruiz X. “The Rhineland Study in DietBB: Prevalence and Characteristics of Metabolic Phenotypes”. The Symposium der Kompetenzcluster der Ernährungsforschung. Freising, Germany, March 2018Presentation
Primary school studentsCowan CSM (cofacilitator) “Microbe Magic” workshop, Local school, Ireland, March 2018Workshop
Clinicians, industryCryan JF. Nutricia Educational Evening, Cork, Ireland, March 2018Presentation
ScientistsCowan, CSM “The microbiota-gut-brain axis across the lifespan modulates stress and cognitive behaviours”; CINP World Congress; Vienna, Austria, June 2018.Presentation
ScientistsOrozco-Ruiz X. “Prevalence and characteristics of metabolic phenotypes: the Rhineland Study (Germany). European Congress of Epidemiology Lyon, France, July 2018Presentation
ScientistsCowan, CSM “Bugs, brain and behaviour: a role for the Microbiome in mental health”; Brain and Mind Centre Seminar Series; AustraliaPresentation
ScientistsCryan, JF: “The dietmicrobiome-gut-brain axis to support brain health”; ECNP 2018; Netherlands; October 2018Presentation
University StudentsHarold, KB “Nurturing the Microbiota-Gut-Brain Axis: Diet, Microbiome and Cognitive Health”, Cork, Ireland, November 2018Presentation
ScientistsCowan, CSM “Towards psychobiotics: Microbiome, brain and behaviour”; Gut-Brain Axis Summit, San Francisco, USA, December 2018Presentation
ScientistsCapuron L. How your weight affects your mood, Royal Society of Medicine, London, January 2019Presentation
General PublicCryan, JF: “The human microbiome: why our microbes could be key to our health”; The Guardian newspaper, UK; March 2018Presentation
General PublicCryan, JF: “The Diet that might cure depression”; The Atlantic newspaper; March 2018Presentation
General PublicCork Discovers; UCC open day; Cork, Ireland; September 2018 (Kirsten Berding Harold assisted)Information stand
General PublicCryan, JF: “Going with your gut instinct: The microbes that control how we feel”; The University Observer, Ireland; November 2018Presentation
Primary School students“Food is Funky” workshop, UCC, Cork, Ireland (Kirsten Harold facilitated); November 2018Workshop

4.3 List of submitted patents and other outputs

Patent licencePartners involvedYearInternational eu or national patentCommentPdf


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