Low dietary fiber intake is a dietary and health concern. Insufficient intake (<25 and 36 g/d, f/m) is frequent in many developed countries including Luxembourg (Alkerwi et al., 2012), and has been related to increased risk of developing various cardio-metabolic complications and higher mortality (McRae et al., 2017) in addition to cancer (Kunzmann et al., 2015). Fiber intake lowers blood lipids (including cholesterol) and is related to anti-inflammatory reactions, fostering a more healthy gut microbiota, with positive systemic effects. However, there is little information to which extent the observed effects are depending on the genetic background of the host (Esworthy et al., 2010). Whole genome sequencing will allow a detailed in-depth investigation of SNPs and other mutations related to the effects of fiber intake.
It has been demonstrated that a higher fiber intake is health beneficial, acting via anti-inflammatory and immune related pathways, which are mediated by the microbiota, but it is not clear to what extent the effects observed depend on the genetic background, which may be an important consideration for explaining health related effects of dietary patterns and interventions. It is the aim of this project to detect genetic variants related to responses of fiber-rich diets.
The proposed project will be carried out by building on an already planned human dietary intervention study in the context of another PhD thesis at DII (student: Erica Grant; MICROH DTU, focussing on the effects of short-term intervention of dietary fiber on the gut microbiota and the immune system, with a particular focus on the microbial mucus foraging). In the current DTU project, a novel and unique aspect will be whole genome analyses (MeGeno) of the healthy volunteers participating in the above interventional study. The genomic information of the healthy individuals will be analysed in relation to the data obtained in the intervention study. Specifically, the genomes analysed (and interesting variants retained) will be re-viewed (further scrutinized via pathway analyses such as KEGG…) and compared in terms of how different individuals would react to short-term dietary fiber intervention in terms of changes in the gut microbiota and inflammatory (CRP, miRNA, cytokines) changes. Immune cell profiling will also be carried out and associated to host genetics.
In a parallel study, samples collected during the cross-sectional ORISCAV-LUX study will be used to investigate the relation of fiber intake (e.g. highest vs. lowest quintile based on Food-Frequency Questionnaires), inflammatory markers (CRP, miRNA, cytokines etc.) and genetic background to verify whether findings from the intervention study can be found also in this population. A more targeted genetic analysis is envisioned, with variants chosen based on results of the intervention trial. This project will generate critical data sets and hypotheses to understand how genetic information can be potentially connected to various aspects of diet and the gut microbiota, making the present PhD project highly innovative, and is expected to result in additional high impact publications.
• Supervisor: Dr Torsten Bohn
• PhD Student: Guilherme Ramos Meyers
This project is part of the i2TRON - PhD Training Program.
i2TRON is a doctoral training unit (DTU) of 20 Ph.D. positions with a strong focus on developing the new generation of translational scientists, who can turn observations in the laboratory, clinical setting or community into interventions that improve health of individuals via innovative diagnostics or treatments. Here we use specific non-communicable diseases (NCDs) as model diseases across auto-immunity/allergy, cancer and neurodegeneration, that are characterized by inflammation as shared key pathogenic mechanism.
i2TRON Individual projects
•Work package 1: Chronic Inflammation
•Work package 2: Immuno-Oncology
•Work package 3: Neuroimmunology