ZIEL Graduate Programme

Title of the PhD thesis
Breaking down Barriers: Understanding the Role of Anaerobic Bacteria in the Skin

Description
Atopic eczema (AE) is an inflammatory skin disorder that is increasing in prevalence (Williams H., et al. 2008; Asher MI., et al. 2006). Most of the research done on this topic has focused on the disturbance of the aerobic microbial layer above the stratum corneum, but inflammation may be caused by the loss of anaerobic microbes lying beneath that skin layer (Nakatsuji T, et al 2013).  The stratum corneum is fractured in patients with AE, and this allows oxygen to reach and disrupt the environment where the anaerobic bacteria live (Tabata N, et al 1998; Nakatsuji, T et al 2013). It has been shown that skin microbiome diversity is lower in AE patients, and the diversity is significantly lower in perforated skin than with it intact. Though this change might solely result from an increase in S. aureus, it also implies the possibility that the size of the anaerobic microbiome may be drastically reduced, which indeed may be the cause of AE (Gong J, et al 2006; Reiger M, et al 2016). Anaerobic bacteria are known to have pH reducing metabolites, such as short chain fatty acids, and, compared to the healthy controls, in AE patients the skin pH is increased (Jang et al 2015).  In this project, we aim to isolate, characterize, and define the role of anaerobic bacteria in the skin, and to determine their relationship to the development of AE.

Title of the PhD thesis
Modulation of the microbial production of dietary biomarkers based on a dietary intervention

Description

Nutrition biomarkers are assumed to be a valuable and objective measure for dietary intake. Unfortunately, only few biomarkers are sufficiently validated so far ^[1]. Furthermore, biomarkers underlie inter- and intra-individual variabilities because they are often influenced by various endo- and exogenous factors such as genetic variability, lifestyle and physiological factors including for example the intestinal microbiota ^[2]. Therefore, the aim of the Food-Biomarker Alliance (FoodBAll) was the validation and systematic evaluation of (novel) biomarkers ^[3,4].

With this project we aim to continue this work on nutrition markers.  With a human intervention study the impact of dietary fibre on certain biomarkers will be investigated^. Another focus is to evaluate the plasticity of the intestinal microbiome under this treatment.

[1]     E. M. Brouwer-Brolsma, L. Brennan, C. A. Drevon, H. van Kranen, C. Manach, L. O. Dragsted, H. M. Roche, C. Andres-Lacueva, S. J. L. Bakker, J. Bouwman et al., The Proceedings of the Nutrition Society, DOI: 10.1017/S0029665117003949.

[2]     A. Scalbert, L. Brennan, C. Manach, C. Andres-Lacueva, L. O. Dragsted, J. Draper, S. M. Rappaport, J. J. J. van der Hooft, D. S. Wishart, The American journal of clinical nutrition, DOI: 10.3945/ajcn.113.076133.

[3]     Ulaszewska MM, Weinert CH, Trimigno A, Portmann R, Lacueva CA, Badertscher R, Brennan L, Brunius C, Bub A, Capozzi F, Rosso MC, Cordero CE, Daniel H, Durand S, Egert B, Ferrario PG, Feskens EJM, Franceschi P, Garcia-Aloy M, Giacomoni F, Giesbertz P, Domínguez RG, Hanhineva K, Hemeryck LY, Kopka J, Kulling S, Llorach R, Manach C, Mattivi F, Migné C, Münger LH, Ott B, Picone G, Pimentel G, Pujos-Guillot E, Riccadonna S, Rist M, Rombouts C, Rubert J, Skurk T, Sri Harsha PSC, van Meulebroek L, Vanhaecke L, Vázquez-Fresno R, Wishard D, and Vergères G. Nutrimetabolomics: An Integrative Action for Metabolomic Analyses in Human Nutritional Studies. Mol Nutr Food Res 2018:e1800384. Doi: dx.doi.org/10.1002/mnfr.201800384

[4]     P. Giesbertz, B. Brandl, Y.-M. Lee, H. Hauner, H. Daniel, T. Skurk, Molecular nutrition & food research, DOI: 10.1002/mnfr.201900921.

Title of the PhD thesis

Microbial Transformation of dietary fatty acids into active metabolites in the gut 

Project description

Dietary fatty acids play an important role in human health and disease, but their Major modulators are not yet identified. Therefore the project aims (1) to identify key players catalyzing the anaerobic transformation of dietary fatty acids in the gut, (2) to investigate the consequences of different dietary interventions in the community composition and activity of microbiota triggering this transformation, and (3) to identify key metabolites formed by the degraders potentially acting as drivers for microbe-microbe and host-microbe interactions. To reach These goals, first transformation of selected fatty acids by minimal consortia will be investigated in vitro using anaerobic Fermenter systems and in vivo in mouse models by metabolomics and -transcriptomics analyses. Then insights will be transferrred to the investigation of key organisms and processes in more complex microbial communities. 

Title of the PhD thesis
Enteroendocrine cells and regulation of feeding behavior

Description
Enteroendocrine cells (EECs) are a key component of the gut epithelium. They interact with the external gut environment and play an active role in the homeostasis of the animal. They release different molecules, from neuropeptides to hormones, that affect their immediate surroundings or travel along the animal to reach distal regions. EECs can respond to a variety of stimuli, such as food presence in the gut, integrity of the epithelium and the composition of the microbiota, by expression of different receptors. However, whether and how EECs modulate animal behavior, such as feeding related decisions, has not been studied at sufficient detail, although it could have broad implications in behavior and metabolism.

Project: The interaction between GR activity and microbiome

Phd Student: Zhanhua Xing

Supervisors: Nina Henriette Uhlenhaut, Britta Spanier

Introduction

Ontologically, the gut is the important organ as it is a place of host-microbiome interaction. The gut microbiome produces macromolecules such as short-chain fatty acids and bile acids, which in turn mediates diverse metabolic processes. The dysfunction in the production of microbiota-derived metabolites due to the (micro-)environmental factors, diet could result in the over activation of immune cells. A potential contribution of this dysfunction has recently been linked to the development of diseases involving inflammation like inflammatory bowel diseases and cancer. The synthetic glucocorticoids such as dexamethasone have been widely used in the clinic to treat severe inflammatory conditions. Besides, glucocorticoids is also known as a potential metabolic regulator. Glucocorticoids is the ligand of glucocorticoids receptor (GR), which is a transcription regulator of genes involved in inflammation, metabolism etc. However the crosstalk between glucocorticoids receptor and gut microbiome is not clear yet. Thus, in this Ph.D. project, we are interested in understanding the impact of glucocorticoids receptor activity on the gut microbiome and vice versa.