DINAMIC
Diet-induced Arrangement of the gut Microbiome for improvement of Cardiometabolic health
The DINAMIC project investigates the interplay between diet, the gut microbiota, and the host in the context of cardiometabolic health. Using state-of-the-art prospective human cohorts, microbiota profiling allows the consortium to identify specific features associated with disease states. Clinical trials based on dietary interventions and fecal microbiota transplantation were designed and are being performed to test causal roles and targeted manipulations of the microbiome under controlled conditions. Mechanistic interactions within the microbiome are further investigated in vitro using continuous culture systems. Meta-omics technologies are employed, aiming at the harmonization or results and the establishment of models towards prediction of detrimental and favourable gut environments with respect to cardiometabolic health. Hence, the expected impact of DINAMIC is to bring light into diet-microbiome interactions for improvement of metabolic conditions, which will contribute to the establishment of appropriate dietary recommendations.
Consortium
| Partner Organization | Partner Country |
|---|---|
| University College Cork | Ireland |
| Université d'Auvergne | France |
| University of Naples Federico II | Italy |
| Amsterdam Diabetes Center AMC-VUmc | The Netherlands |
| University of Copenhagen | Denmark |
| MetaGenoPolis | France |
| King's College Hospital | United Kingdom |
Highlights
- Arrhythmic gut microbiome signatures predict risk of Type 2 diabetes in population studies.
- Heritable components of the human fecal microbiome are associated with visceral fat.
- Breastmilk-promoted bifidobacteria produce aromatic lactic acids in the infant gut.
- Mediterranean diet intervention in overweight and obese subjects lowers plasma cholesterol and causes changes in the gut microbiome and metabolome independently of energy intake.
- A Mediterranean diet intervention reduces the levels of salivary periodontopathogenic bacteria in overweight and obese subjects.
- Red wine consumption is associated with increased gut microbiota α-diversity in three independent cohorts.
- Improvement of insulin sensitivity after lean donor feces in metabolic syndrome is driven by baseline intestinal microbiota composition.
- Combining a mediterrean diet with lean donor fecal transplantation (FMT) has no synergistic effect on glucose metabolism. Beneficial effects of the mediterreanean diet on the gut microbiota (e.g. increase in diversity) may prohibit engraftment of donor bacterial strains.
- The use of reference communities in amplicon sequencing studies allows to avoid the analysis of artefact sequences.
Products
Reports
Endreport
Studies from the consortium reinforced the idea that the gut microbiome is important for cardiometabolic health and identified specific taxa and microbiome signatures associated with risk factors. The work also provides further evidence that a Mediterranean diet is an efficient strategy to reduce inflammation status during controlled energy intake, which might benefit public health by limiting people at risks of developing cardiometabolic diseases.
In the course of the project, we were able to investigate and provide valuable novel insights to the relationships between diet, the microbiota and human health at different levels. In the KORA cohort study, we were able to correlate, via shotgun metagenomics, metabolic pathways to the proposed bacterial taxa with disrupted rhythmicity potentially involved in the development of T2D. By integrating together microbiome, diet and phonotypic information in over 2,700 participants from the TwinsUK cohort, we showed that the microbiome may play a predominant role in mediating the effects of diet on host metabolic health. Integration of metagenomics and metabolomics data enabled us to demonstrate that the gut microbiome shapes host metabolome. Lastly, using prospective data, we observed that T2D development is preceded by a significant alteration of the composition of the gut microbiome.
Via interventions studies, we could demonstrate that an isocaloric, 8-week intervention with a Mediterranean diet in obese and overweight subjects with cardiometabolic risk in Italy without any change in individual energy intake, nutrient intake and physical activity leads to multiple and beneficial changes in the microbiome and systemic metabolome. We also observed a beneficial effect of the Mediterranean diet on plasma lipids after two weeks of intervention in subjects with metabolic syndrome in the Netherlands. However, there was no additional beneficial effect of combining the Mediterrean diet and lean donor fecal microbiota transplantation (allogenic) on stable isotope-determined (peripheral) insulin sensitivity compard to own feces transplantation.
In vitro, we could show that specific components of the Mediterranean diet (e.g. oil from olives and nuts) modulate the occurrence and activity of microbial taxa with consequences on metabolomes produced. Using metabolomics for analysis of the samples from the Mediterranean diet intervention study in Italy, increased levels of biomarkers of wholegrains, legumes, vegetables and nuts, as well as reduced concentrations of biomarkers of meat and protein degradation products were observed. Shotgun sequencing allowed the reconstruction of metagenome-assembled genomes to show that approximately 10% of the gut microbiome was rearranged by the Mediterranean diet, which favoured butyrate-producing taxa such as Faecalibacterium prausnitzii and members of the genus Roseburia.
Standardization work with high-throughput 16S rRNA gene amplicon analysis demonstrated that handling of artifact sequences during bioinformatic processing requires careful attention to avoid the generation of misleading findings. A threshold of relative abundance of 0.25% is more appropriate than singleton removal, although study-specific analysis strategies are mandatory. The new concept of effective richness will help comparing results across studies.
Communication & Dissemination Activities
| Target group | Authors | Means of communication |
|---|---|---|
| Diabetes researchers, internists, dieticians | Prof. Nieuwdorp (AMC), EASD 2018 Lisbon | Oral presentation |
| Scientists | APC: Diet-induced Arrangement of the gut microbiome for Improvement of Cardiometabolic health, Gut Health Day Conference, Netherlands 05/12/2019 | Plenary talk |
| Scientists | Le Roy (Kings College), Heritability of the gut microbiome. University of Luxembourg, 2020 | Oral presentation |
| Scientists | Le Roy (Kings College), Understanding diet-gut microbiota interaction in health and disease through observational studies., Gut Day, Amsterdam, The Netherland, 2019 | Oral presentation |
| Scientists | Le Roy (Kings College), Heritability of the gut microbiome. Human microbiome: Resistance and disease EMBO Symposia, Kalyani, India, 2019 | Oral presentation |
| Scientists | Le Roy (Kings College), Dissecting the role of the gut microbiota and diet on visceral fat mass accumulation. Nutrition 2019, Baltimore, USA, 2019 | Oral presenation |
| Scientists | Bell (Kings College), The role of the gut microbiota in human type 2 diabetes: insights from multi-omic studies, European Association for the Study of Diabetes (EASD) 54th annual meeting, Berlin, Germany, October 2018. | Oral presentation |
| Scientists | Le Roy, Visconti, Falchi, Menni, Bell, Spector (Kings College). Christensenella association with visceral fat mass is species dependent. 2018, Keystone, Banff, Canada, 2018 | Poster presentation |
| Scientists | Oral presentation: Le Roy, Bowyer, Steve, Spector, Forslund, Bell (Kings College), Heritability of antibiotic resistance in the Human gut microbiome. 2017, Welcome trust conference, Cambridge, UK, 2017 | Oral presenation |
| Scientists | Roager, HM, UCPH, Mediterranean diet changes the intestinal and systemic metabolome in overweight/obese adults; Nordic Metabolomics Conference 2018, Aug 26-28 2018 | Poster Presenation |
| Scientists | Roager, HM, UCPH; Mediterranean diet changes the intestinal and systemic metabolome in overweight/obese adults; Clinical Metabolomics Copenhagen Conference, Oct 25, 2018 | Poster presenation |
| Scientists | Roager, HM, UCPH; Exploring diet-microbiome interactions by metabolomics; Clinical Metabolomics Copenhagen Seminar, June 13, 2019 | Invited oral presentation |
| Scientists | Roager, HM , UCPH; Metabolomics to elucidate gut microbial-host interactions important for health, Nordic Metabolomics Workshop 2019, Oct 31 2019 | Invited oral keynote presentation |
| Scientists | Lars Ove Dragsted, UCPH; Reflections of gut microbiota‐diet interaction in plasma and urine; results on metabolomics, JPI day – Dutch Gut day December 5th 2019 – Amsterdam UMC, location AMC | Invited oral presentation |
| Scientists | Lars Ove Dragsted, UCPH; Gut-host co-metabolism explored by metabolomics, Sciene Day: ZIELkolaus Nutrition & Microbiome, TUM, 12/2019 | Invited oral presentation |
| Scientists | De Filippis, F., Laiola, M., Mennella, I., Vitaglione, P., Ercolini (UNINA), Dietary intervention with a Mediterranean-style diet modulates gut microbiome in healthy obese subjects. 7th International Human Microbiome Consortium Meeting 2018, Killarney, IR, 26-28 June 2018 | Poster presentation |
| Scientists | Laiola, M., De Filippis, F., Mennella, I., Vitaglione, P., Ercolini, D (UNINA). 2018. Changes in the salivary microbiota after a Mediterranean diet-based intervention in overweight subjects. 7th International Human Microbiome Consortium Meeting 2018, Killarney, IR, 26-28 June 2018. | Poster presentation |
| Scientists, Industry and Policiy makers | De Filippis, F (UNINA). Modulation of the gut microbiome through diet for a healthy living. “Korea-Italy Bilateral Workshop on Human Microbiome” organized by the Italian Embassy in South Korea within BioKorea2018 Convention, Seoul, South Korea, 10 May 2018 | Invited oral presentation |
| Scientists | De Filippis, F., Laiola, M., Gallo, M.A., Giacco, R., Rivellese, A.A., Vitaglione, P., Ercolini, D. (UNINA): Modulation of gut microbiota through Mediterranean diet in obese adults. XXXIX National Congress of the Italian Society of Human Nutrition (SINU2018), Napoli, IT, 19-21 November 2018 | Invited oral presentation |
| Scientists | Vitaglione, P., Rivellese, A.A., Ercolini, D. (UNINA), Vitale, M., Giacco, R., De Filippis, F., Mennella, I. Biomarkers of adherence tot he mediterranean diet: which contribution from the gut microbiota? XXXIX National Congress of the Italian Society of Human Nutrition (SINU2018), Napoli, IT, 19-21 November 2018 | Oral presentation |
| Scientists | De Filippis, F (UNINA). Gut microbiome and diet inter-connections for a healthy living. MIBIOC – The way of the microbiota in cancer. Milan, IT, 21-22 November 2019 | Invited oral presentation |
| Scientists | De Filippis, F., Laiola, M., Giacco, R., Rivellese, A.A., Vitaglione, P., Ercolini, D. (UNINA). Mediterranean-style dietary intervention promotes the production of beneficial metabolites and modulates gut microbiome in healthy obese subjects. 5th International Conference on Microbial Diversity 2019, Catania, IT, 25-27 September 2019 | Oral presentation |
| Scientists | Ercolini, D. (UNINA). Impact of Mediterranean Diet on the gut Microbiota. Conference :“Le basi farmacologiche dei nutraceutici“. Naples, IT, 29-30/03/2019. | Oral presentation |
| Scientists | Ercolini, D.(UNINA). Solid foods, junk foods, Mediterranean Diet and gut Microbiota. Conference :“10th Conference of Prebiotics probiotics and new foods“. Rome, IT, 09/09/2019. | Oral presenation |
| Scientists | Vitaglione, P., De Filippis, F., Mennella, I., Giacco, R., Rivellese, A.A., Ercolini, D. (UNINA), A dietary intervention with a Mediterranean diet in subjects at risk of cardiovascular disease: effects on metabolism and on gut microbiome XXXIII European Nutrition Conference (FENS2019), Dublin, Ireland, 15-18 October 2019 | Oral presentation |
| Scientists | Sandra Reitmeier (TUM): Arrhythmic gut microbiota members as diagnostic risk factors for Type-2 Diabetes, UEG Conference (Barcelona Oct. 2019) | Poster presentation |
| Scientists | Sandra Reitmeier (TUM): Arrhythmic microbiota signatures improve diagnostic profiling of Type-2 diabetes in a prospective population cohort, Keystone Symposium (Killarney Oct. 2019) | Poster presentation |
| Scientists | Sandra Reitmeier (TUM): Gut microbiota profiling in a prospective population cohort in relation to metabolic health, Conference (Seeon June. 2019) | Oral presentation |
| Scientists | Sandra Reitmeier (TUM): Gut microbiota profiling in a prospective population cohort in relation to metabolic health, DDW (San Diego May. 2019) | Oral presentation |
| Scientists | Sandra Reitmeier (TUM): Handling of spurious molecular species influence the outcome of high-throughput 16S rRNA gene amplicon profiling, #SciGQ2019 the 9th Gene Quantification Event -- qPCR dPCR & NGS 2019 (Freising March 2019) | Oral presentation |