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.
|University College Cork
|University of Naples Federico II
|Amsterdam Diabetes Center AMC-VUmc
|University of Copenhagen
|King's College Hospital
- 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.
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.