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
HEALTHMARK
2017-03-01
2021-02-28
Prof Ute Nöthlings
University of Bonn (UB)
Germany

Consortium

Partner Organization Partner Country
German Center for Neurodegenerative Diseases, "Deutsches Zentrum für Neurodegenerative Erkrankungen e. V." (DZNE) Germany
National Research Institute for Agriculture, Food and Environment, “Institut national de recherche pour l’agriculture, l’alimentation et l’environnement” (INRAE) France
University College Cork/Teagasc (UCC/Teagasc) Ireland
Edmund Mach Foundation, “Fondazione Edmund Mach” (FEM) Italy

1. Overall project description


1.1 Summary

HEALTHMARK investigated 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 project, organized in five work packages (WP) comprised two observational and two intervention studies. In WP1, the University of Bonn (UB) using the DOrtmund Nutritional and Anthropometric Longitudinally Designed Study identified long-term body mass index trajectories and observed their association with cardiometabolic risk markers (CRM) such as interleukin-18. Besides, long-term overweight was associated with decreased levels of indole-3-acetic acid and several amino acids, including indole-3-carboxaldehyde were associated with elevated C-reactive protein (CRP). Finally, carbohydrate intake was associated with the relative abundance of some gut bacteria, Phascolarctobacterium, Dialister, and Desulfovibrio. In WP2, the German Center for Neurodegenerative Diseases, "Deutsches Zentrum für Neurodegenerative Erkrankungen e. V." (DZNE) using the Rhineland Study developed novel methods to automatically segment body fat distribution from MRI recordings. It was also observed that branched-chain amino acids (BCAA) and aromatic amino acids (AAA) metabolites are important biomarkers of some CRM and partial mediators of the association between visceral adipose tissue and CRM. In WP3, the National Research Institute for Agriculture, Food and Environment, “Institut national de recherche pour l’agriculture, l’alimentation et l’environnement” (INRAE) using the Obesity Study measured plasma levels of tryptophan, and its metabolites, other AAA, and BCAA  before and after surgery-induced weight loss. Severe or morbid obesity was associated with increased ratio kynurenine/tryptophan, high plasma levels of 5-hydroxyindole- 3-acetic acid, and low plasma levels of tryptophan, serotonin, indole-3-propionic acid, indole-3-acetic acid, indole-3-lactic acid, and indoxyl sulfate. Moreover, kynurenine and tryptophan indole metabolites were associated with CRP and interleukin-6. In WP4, the University College Cork/Teagasc (UCC/Teagasc) conducted a clinical investigation on the efficacy of probiotic Lactobacillus mucosae DPC6426 as a nutritional agent to modulate tryptophan metabolism and metabolic biomarkers in mildly hypercholesteremic adults. The counts of Lactobacillus increased in stool samples, but the probiotic had no effect on either total blood cholesterol or microbial diversity. In WP5, the Edmund Mach Foundation, “Fondazione Edmund Mach” (FEM) developed and performed targeted metabolomic profiling of biofluids for the putative biomarkers of metabolic health for the WPs, 672 urine samples from WP1, 1000 plasma samples from WP2, and 104 plasma samples from WP3. FEM also built an in-house spectral library for structural elucidation and comparison of metabolites from these samples. Some samples also underwent untargeted metabolomics profiling.


1.2 Highlights

HEALTHMARK investigated 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. HEALTHMARK observed the association of long term body mass index, visceral adipose tissue and severe or morbid obesity with cardiometabolic risk markers. It also established the link of tryptophan and its metabolites, other aromatic amino acid metabolites and branched-chain amino acids with cardiometabolic risk markers. The project also observed the impact of dietary intake, particularly carbohydrate intake on the composition of the gut microbiome. In addition, probiotic Lactobacillus mucosae DPC6426 did not show effect on total blood cholesterol or gut microbial diversity. Finally, a validated state-of-the-art targeted metabolomic profiling method was used to quantify metabolites in the biofluids within the consortium.



4. Impact


4.1 List of publications

AuthorsTitleYear, Issue, PPPartners NumberDoiPdf
Cowan CSM*, Hoban AE, Ventura-Silva AP, Dinan TG*, Clarke G*, Cryan JF*Gutsy Moves: The Amygdala as a Critical Node in Microbiota to Brain Signaling2018, 40, 1700172DOI: 10.1002/bies.201700172
Oluwagbemigun K*, Buyken AE, Alexy U, Schmid M, Herder C, Nöthlings U*Developmental trajectories of body mass index from childhood into late adolescence and subsequent late adolescenceyoung adulthood cardiometabolic risk markers2019, 18(1), 9https://doi.org/10.1186/s12933-019-0813-5
Anesi A*, Rubert J*, Oluwagbemigun K*, Orozco-Ruiz X*, Nöthlings U*, Breteler MMM*, Mattivi F*Metabolic profiling of human plasma and urine, targeting tryptophan, tyrosine and branched chain amino acid pathways. 2019, 9(11), 261DOI: 10.3390/metabo9110261
Estrada, S, Lu, R, Conjeti, S, Orozco‐Ruiz X*, Panos‐Willuhn J, Breteler MMB*, Reuter M.FatSegNet: A fully automated deep learning pipeline for adipose tissue segmentation on abdominal dixon MRI. 2020, 83 (4), 1471–1483https://doi.org/10.1002/mrm.28022
Oluwagbemigun K*, Anesi A*, Ulaszewska M*, Clarke G*, Alexy U, Schmid M, Roden M, Herder C, Mattivi F*, Nöthlings U*Longitudinal investigation into the relationship of amino acids and indole metabolites with long-term body mass index and cardiometabolic risk markers in young individuals. 2020; 10, 6399DOI: 10.1038/s41598-020-63313-z
Cussotto S, Delgado I*, Anesi A*, Dexpert S, Aubert A, Beau C, Forestier D, Ledaguennel P, Magne E, Mattivi F*, Capuron L*Microbial tryptophan metabolites are differentially affected by inflammation in obesity2020; 11, 557DOI: 10.3389/fimmu.2020.00557
Oluwagbemigun K*, O'Donovan AN, Berding K, Lyons K, Alexy U, Schmid M, Clarke G*, Stanton C*, Cryan J*, Nöthlings U*Long-term dietary intake from infancy to late adolescence is associated with gut microbiota composition in young adulthood. 2021, 113 (3), 47–656https://doi.org/10.1093/ajcn/nqaa340

4.2 Presentation of the project

Target groupAuthorsMeans of communicationHyperlinkPdf
ScientistsCryan, J.F. (UCC/Teagasc),“The microbiome – A key regulator of brain & behaviour across the lifespan”, Santander Biomedical Lecture, Santander, Spain, March 2017Special lecture
ScientistsStanton, C. (UCC/Teagasc), “Gut microbiota in developing neonates”, 116th Abbott Nutrition Research Conference, Abott Nutrition Health Institute, Ohio, USA, April 2017Presentation
ScientistsStanton, C. (UCC/Teagasc) “Synbiotics effects on extra-intestinal targets”, International Scientific Association of Probiotics and Prebiotics, Chicago, USA, June 2017Presentation
Scientists, government representatives, industry, farmersStanton, C. (UCC/Teagasc), “Microbiome-based solutions for early life nutrition”, Teagasc Authority Meeting, Kilkenny, Ireland, July 2017Presentation
ScientistsDinan, T. G (UCC/Teasgac), “Microbes and brain function”, FEMS (Federation of European Microbiological Societies) meeting, Valencia, Spain, July 2017Presentation
ScientistsCryan, J.F. (UCC/Teagasc), “Gut feelings: The microbiota as a key regulator of brain and behaviour across the lifespan”. International Society for Nutritional Psychiatry Research, Bethesda, USA, July 2017Plenary lecture
AcademicFallahghohroudy, A., Oluwagbemigun, K. (UB), “The relation between the dietary patterns (short-term and long-term) on the gut microbiota: systematic review”, Master course, project practical, Bonn, July 2017Master’s course report
ScientistsKloster, T., Oluwagbemigun, K. (UB), “The influence of the gut microbiota on blood lipids and short-chain fatty acids: a systematic review”, Master course, project practical, Bonn, July 2017Master’s course report
Scientists, industryCowan, C. S. M., Dinan, T. G., Cryan, J.F. (UCC/Teagasc), “Towards psychobiotics: Microbiome, brain and behaviour”, Gut-Brain Axis Summit, San Francisco, C.A., August 2017Presentation
PhysiciansCryan, J.F. (UCC/Teasgac), “A gut (microbiome) feeling about the brain” Nutricia Nutrition, Royal College of Physicians, London, November 2017Presentation
ScientistsMattivi, F., Nöthlings, U., Oluwagbemigun, K. (UB and FEM), "Gut microbiota and tryptophan metabolism - implications for human health", 9th Probiotics, Prebiotics & New foods, Nutraceuticals and Botanicals for Nutrition & Human and Microbiota Health. Rome; Italy, September 2017Invited lecture
ScientistsDinan, T. G. (UCC/Teagasc), “Psychobiotics”, 17th International Forum on Mood and Anxiety Disorders, Madrid, Spain, December 2017Presentation
General public & scientistsCowan, C.S.M., Hoban, A. E., Ventura-Silva, A. P., Dinan, T. G., Clarke, G., Cryan, J. F. (UCC/Teagasc), “BioEssays: Gutsy Moves: The Amygdala as a Critical Node in Microbiota to Brain Signaling”, December 2017Video on microbiota & amygdala interactions to support review article published in BioEssays: youtube.com/watch?v=O5gvxVJjX18
ScientistsCowan, C.S.M., Hoban, A. E., Ventura-Silva, A. P., Dinan, T. G., Clarke, G., Cryan, J. F. (UCC/Teagasc), “BioEssays: Gutsy Moves: The Amygdala as a Critical Node in Microbiota to Brain Signaling”, January 2018Journal cover art
ScientistsCowan, C.S.M., Dinan, T. G., Cryan, J. F. (UCC/Teagasc), “Gut-brain axis: Focus on the brain and behaviour.”, The 5th Nutrition Winter School, Levi, Finland, January 2018Presentation
Scientists, industryCryan, J.F. (UCC/Teagasc),“New advances: Diet and microbiome.” International Life Science Institute – North America Annual Meeting, Bermuda, January 2018Presentation
AcademicPetri N., Mattiivi F. (FEM), “Sviluppo e prima validazione di un metodo per la quantificazione dei metaboliti del triptofano nel plasma umano mediante cromatografia liquida abbinata a spettrometria di massa”, Master Thesis LM-61, University of Florence, February 2018Master thesis
ScientistOrozco-Ruiz X. (DZNE), “The Rhineland Study in DietBB: Prevalence and Characteristics of Metabolic Phenotypes”. The Symposium der Kompetenzcluster der Ernährungsforschung. Freising, Germany, March 2018.Presentation
ScientistsOrozco-Ruiz X. (DZNE), “Prevalence and characteristics of metabolic phenotypes: the Rhineland Study (Germany). European Congress of Epidemiology, Lyon, France, July 2018.Presentation
ScientistsOluwagbemigun, K., (UB), “Developmental trajectories of body mass index from childhood into late adolescence and subsequent late adolescence young adulthood cardiometabolic risk markers”, 26th European Congress on Obesity, 29 April 2019.Poster
ScientistsOluwagbemigun, K. (UB), “Longitudinal investigation into the relationship of amino acids and indole metabolites with long-term body mass index and cardiometabolic risk markers in young individuals”, DietBB annual meeting. 11 October 2019Poster
ScientistOrozco-Ruiz X. (DZNE), “Association of visceral and subcutaneous adipose tissue with metabolic health in the Rhineland Study”, DietBB annual meeting. 11 October 2019Poster
ScientistsCapuron, L.. (INRAE), “Nutritional habits, obesity and neuropsychiatric symptoms”, International Society for Nutritional Psychiatry Research, London, UK, October 2019.Presentation
ScientistsOrozco-Ruiz X. (DZNE), “Association of Tryptophan, Tyrosine and Branched Chain Amino acids metabolites with abdominal obesity and cardiometabolic risk factors", CHARGE meeting, Hoston Tx, 29-31 January 2020Poster
ScientistsDelgado, I., Capuron, L., (INRAE), “Adiposity-driven inflammatory mechanisms in obesity: role in neuropsychiatric comorbidities”, ECOICO Online 2020, via Zoom, September 2020Presentation
ScientistsOrozco-Ruiz X. (DZNE), “Association of BCAAs and AAAs metabolites with abdominal fat and cardiometabolic risk factors”. DietBB annual meeting. 2 October 2020Poster
ScientistsAnesi, A. (UB, FEM) “Metabolic profiling of human plasma and urine, targeting tryptophan, tyrosine and branched chain amino acid pathways”, Metabolomics 2020. October 27-29, 2020Poster
ScientistsCryan J.F. (UCC/Teagasc) “Microbiota and the Brain”, Online Retreats with the World Leaders (Italy), 2020Workshop
ScientistsCryan J.F. (UCC/Teagasc) “Microbiota-Gut Axis along human life, GMFH 2020 Wold Summit (Spain), 2020Conference
ScientistsCryan J.F. (UCC/Teagasc) “Gut microbiome, brain and behavior”, Molecular Mechanisms Linking the Microbiome and Human Health (USA), 2020Conference
ScientistsCryan J.F. (UCC/Teagasc) “A Gut Feeling about the Brain: Microbiome as a Key Regulator of Neurodevelopment and Behaviour”, Congresso Futuro Chile (Chile), 2020Conference
ScientistsCryan J.F. (UCC/Teagasc) “Gut Feelings: Diet-Microbiome-Gut- Brain axis”, Gran Sasso Forum (online), 2020Seminar
Cryan J.F. (UCC/Teagasc) “Microbiome and Mental Health”, NYAS Webinar (online), 2020Seminar
Primary school studentsCowan, C.S.M. (co-facilitated) (UCC/Teagasc), “Budding Biologist” workshop, UCC, Ireland, May 2017 Workshop
General publicCryan, J.F. (UCC/Teagasc), “Feed your microbes – nurture your mind”, TEDx H’apenny Bridge, Dublin, June 2017Presentation
Primary school studentsCowan, C.S.M. (co-facilitated) (UCC/Teagasc), “Microbe Magic” workshop, Local school, Ireland, November 2017 Workshop
General publicCowan, C.S.M. (assisted) (UCC/Teagasc), "Science Week:" UCC open day, November 2017 Information stand
General publicBerding K. (UCC/Teagasc), “You are what you eat: Diet, Microbiota and Health”, World Microbiome Day (online)Seminar
General publicBerding K. (UCC/Teagasc), “Food, mood and microbes”, Conversation café, Cork, 2020Round table discussion

4.3 List of submitted patents and other outputs

Patent licencePartners involvedYearInternational eu or national patentCommentPdf

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