Research Projects

Abstract

Research into health and well-being has historically been neglected in critical populations, particularly in women, children, and socioeconomically disadvantaged groups. This global issue, characterized by systemic neglect and underfunding, underscores an urgent need for research centres to spearhead transformative initiatives. A multidisciplinary approach is pivotal in addressing these disparities effectively. Our proposal introduces the establishment of the "U-MaMi" Research Centre of Excellence, designed as an integrated ecosystem to drive impactful research, innovation, education, policy, and community engagement, with a keen focus on health equity and microbiome-centric research. This ecosystem involves principal investigators and their team members from key disciplines to achieve these goals: microbiology and microbiome research (Sarah Lebeer), bioethics (Kristien Hens), general medicine (Veronique Verhoeven), paediatrics (Stijn Verhulst), ear-nose-throat specialication (Olivier Vanderveken), sociology (Karel Neels) and marketing (Annouk Lievens). With the chosen name for our centre, "U-MaMi," we do not only recognize the pivotal role of mothers and 'maternal microbes' in shaping the microbiome and health of their children, but also emphasize the importance of a united and inclusive perspective on health and health equity to drive transformative actions.

Researcher(s)

• Promoter: Lebeer Sarah
• Co-promoter: Hens Kristien
• Co-promoter: Lievens Annouk
• Co-promoter: Neels Karel
• Co-promoter: Vanderveken Olivier
• Co-promoter: Verhoeven Veronique
• Co-promoter: Verhulst Stijn

Research team(s)

• Laboratory of Applied Microbiology and Biotechnology (LAMB)

Project type(s)

• Research Project

Abstract

Respiratory tract infections and infections of the vaginal mucosa, though affecting different anatomical regions, both represent significant global health challenges due to their viral origins, potential complications, and the burden they place on healthcare systems. Respiratory tract infections, such as influenza, respiratory syncytial virus (RSV), and coronaviruses, are among the leading global causes of morbidity and mortality. While most respiratory infections are of viral origin, secondary bacterial infections significantly increase disease severity, antibiotic use, and the development of multidrug resistance. Similarly, viral infections of the vaginal mucosa, such as human papillomavirus (HPV) and human immunodeficiency virus (HIV), pose major global health risks. HPV, for example, is the most common sexually transmitted infection and is responsible for nearly all cases of cervical cancer, while HIV continues to result in substantial morbidity and mortality through its progressive immune system degradation. Both respiratory and vaginal viral infections not only cause high disease burdens but also increase susceptibility to secondary bacterial infections or co-infections, thereby exacerbating health outcomes. These similarities highlight the need for innovative therapeutic strategies to address these complex infections, potentially including live biotherapeutic products, to mitigate their global impact. 3 It is nowadays well established that the microbiome at the respiratory and vaginal mucosa have an important gatekeeper function for our health. The microbiome can protect against viral infections, but also significantly be disturbed, so that symptoms are increased. Nevertheless, few studies have attempted to target the mucosal microbiota as a strategy to reduce the risk of respiratory infections9. The laboratory of applicant prof. Sarah Lebeer has gained pioneering insights into the role of the mucosal microbiome in health in projects such as ProCure (wwww.procureproject.be) and Isala (https://isala.be/en/) and collected a unique dataset of the vaginal and nasal microbiome in health versus various diseases. In addition, the lab has a unique culture collection or microbiome bank of supposedly beneficial bacteria, mainly lactobacilli, which have therapeutic potential based on preclinical data, mainly from in vitro and cell models. To explore the clinical potential of these strains, clinical trials are required, but they are not straightforward for live biotherapeutic products (LBPs), because they will have to form a new regulatory route compared to standard single-molecule drugs. This SEP project is aimed taking the next steps into the valorization of the microbiome bank. The SEP funding will be applied to optimize the datapackage of the existing culture collection, by performing additional experiments on valorization-readiness of the different strains.

Researcher(s)

• Promoter: Lebeer Sarah

Research team(s)

• Laboratory of Applied Microbiology and Biotechnology (LAMB)

Project type(s)

• Research Project

Abstract

Preterm birth (PTB) remains a significant global health challenge, affecting millions of pregnancies annually. Despite extensive research, preterm birth rates continue to rise worldwide. The vaginal microbiome composition, a.k.a. microorganisms inhabiting the vaginal ecosystem, influences preterm birth risk and neonatal health outcomes. Variation in the vaginal microbiome composition, particularly decreased lactobacilli abundance and colonization by Group B Streptococcus, correlates with a higher risk of preterm labour. Worryingly, current antibiotic therapies have limitations, including emerging resistance and disturbance of host microbiota balance. Thus, there is a need to investigate predictive and novel preventive strategies to decrease preterm birth rates. As predictive strategies, the present project proposes (a) to explore the already available clinical data using novel bioinformatic tools for the identification of predictive factors (b) to map the vaginal microbiome composition and elucidate its interacting networks (not explored before). In addition, as a preventive strategy, we aim to screen the host lab lactobacilli isolates collection against Group B Streptococcus isolates. Finally, utilizing advanced techniques such as the vagina-on-a-chip model, we will select ten lactobacilli and uncover their interaction with GBS within a physiologically relevant environment, guiding the selection of probiotic candidates.

Researcher(s)

• Promoter: Lebeer Sarah
• Co-promoter: Condori Sandra
• Co-promoter: Donders Gilbert
• Fellow: Marin Andreea-Monica

Research team(s)

• Laboratory of Applied Microbiology and Biotechnology (LAMB)

Project type(s)

• Research Project

Abstract

Lactobacillaceae are the best documented family of beneficial bacteria with crucial roles in human reproduction, fermented foods, pollinator health, and other "one health"-related functions. However, we know surprisingly little about the beneficial activities of lactobacilli, beyond lactic acid production. Recently, we discovered that, despite the relatively small genomes of most Lactobacillaceae (about 3 Mbp), many species do contain large gene clusters, such as non-ribosomal peptide synthetases (NRPS). Preliminary results indicate unusual chemistry and valuable genetic elements and metabolites, which could contribute to insights into microbial ecology and synthetic re-engineering of non-ribosomal peptides (NRPs). This diverse class of molecules is known to elicit different effects, ranging from antimicrobial activity to immunomodulation and anti-cancer effects. We believe these molecules play a key role in explaining the lactobacilli dominance in specific niches, such as the human vagina and vegetable fermentations. Using in silico analysis, the diversity of NRPS systems in Lactobacillaceae will be classified. The most interesting NRPs will be chemically and functionally characterized in view of their mode of action. Using genetic engineering, we will gain more insight into the important features of these NRPs and explore possibilities for enhancing activity.

Researcher(s)

• Promoter: Lebeer Sarah
• Co-promoter: Vandenheuvel Dieter
• Fellow: Van Hee Matisse

Research team(s)

• Laboratory of Applied Microbiology and Biotechnology (LAMB)

Project type(s)

• Research Project

Abstract

The crucial role of the vaginal microbiome in women's health cannot be overstated. Disruptions to this ecosystem by pathobionts can result in the development of prevalent vaginal conditions, including bacterial vaginosis, aerobic vaginitis, and vulvovaginal candidiasis. These infections not only affect physical health but have also broader implications for women's well-being, society, and the economy. Current treatment methods involve the use of antibiotics or probiotics, but concerns about emerging antimicrobial drug resistance and a lack of solid evidence for the efficacy of current probiotics are frequently raised. This PhD project explores an innovative approach using synthetic communities (SynComs) to develop vaginal therapeutics. First, a top-down approach will be used to screen and select consortia of vaginal microbiota, emphasizing synergistic interactions and eliminating antagonistic effects. A bottom-up approach will validate the top-down findings, providing defined communities suitable for automation and scaling up. Simultaneously, these defined SynComs will undergo testing for their probiotic potential, comparing them with single strains through in vitro anti-pathobiont assays, community fitness analyses, and implementation into cutting-edge vaginal cell models. This research project will offer ground-breaking insights into a novel approach to establishing robust, safe, and effective microbiome-targeted therapies.

Researcher(s)

• Promoter: Lebeer Sarah
• Co-promoter: Allonsius Camille
• Co-promoter: Donders Gilbert
• Co-promoter: Verhoeven Veronique
• Fellow: Victor Maline

Research team(s)

• Laboratory of Applied Microbiology and Biotechnology (LAMB)

Project type(s)

• Research Project

Abstract

Urbanization is a key global trend. Despite its many advantages, urban life presents significant challenges to human health, potentially disrupting the delicate balance of the human microbiome. Given its pivotal role in preventing local infections and inflammatory diseases, it is crucial to understand the effects of urbanization on the skin microbiome. Therefore, this innovative project aims to investigate urban factors or combinations thereof that impact the skin microbiome composition, and identify potentially beneficial skin bacteria resistant to these urban factors. To address this challenge, we will use comprehensive skin microbiome and metadata from several microbiome projects, which we will combine with public environmental data to obtain groundbreaking insights. Furthermore, we will establish innovative in vitro microbial-based testing platforms suitable to represent children or adults. This will enable us to experimentally validate the impacts of urban-associated factors on the skin microbiome to substantiate the observed microbiome study associations, which has seldom been done in the past. As a final innovative aim, we will identify and characterize beneficial skin microorganisms that mitigate the negative effects of harmful urban factors on the skin. These novel insights will be critical for the advancement of skin disease prevention strategies and promoting overall human health in urban environments.

Researcher(s)

• Promoter: Spacova Irina
• Co-promoter: Gehrmann Thies
• Co-promoter: Lebeer Sarah

Research team(s)

• Laboratory of Applied Microbiology and Biotechnology (LAMB)

Project type(s)

• Research Project

Abstract

The composition of the vaginal microbiome is crucial for women's health. Its composition changes significantly with age, environment, lifestyle, physiological condition, biogeography and ethnicity. Yet we lack a in-depth comprehension of the factors fostering a healthy vaginal ecosystem, slowing down the development of much needed effective diagnostic and therapeutic approaches. Notably, there exists a substantial knowledge deficit regarding the vaginal microbiome in regions like Sub-Saharan and Central Africa. This PhD project aims to bridge this gap by delving into the vaginal microbiome dynamics in Central Africa (Cameroon) using state-of-the-art microbiome analyses. The study encompasses four distinct cohorts: healthy women residing in rural and urban areas, HIV-positive pregnant women, and HIV-negative pregnant women in Cameroon. Each participant contributes four vaginal swabs for comprehensive analysis: eNat swabs for DNA extraction and microbiome sequencing, Eswab for culturomics and metabolomics, a sterile swab for vaginal pH measurement, and another sterile swab for bacterial vaginosis assessment using the Nugent score. Furthermore, participants provide valuable insights into their dietary patterns, socio-economic status, personal hygiene practices, as well as reproductive and sexual health via a comprehensive survey. By integrating these metadata with microbiome data analysis, this research aims to unravel novel insights into the vaginal microbiome in Cameroon, identifying new avenues for diagnostic and therapeutic interventions.

Researcher(s)

• Promoter: Lebeer Sarah
• Fellow: Kenfack Zanguim Marie Josiane

Research team(s)

• Laboratory of Applied Microbiology and Biotechnology (LAMB)

Project type(s)

• Research Project

Abstract

Cystic fibrosis (CF) is the most common hereditary life-threatening condition in Belgium and is included since 2019 in the newborn screening program in Flanders to promote early diagnosis and treatment and consequently outcome. Antibiotics and the more recent modulator therapies are crucial in the treatment of persons with CF, but they both have limitations. For instance, even with modulator therapy, structural lung damage persist, pathogens remain present in high numbers, and exacerbations still occur. Complementary and/or alternative treatments for persons with CF remain thus of high interest, especially preventive therapies that can be used in early stages. The use of beneficial bacteria from the airway microbiome is an appealing option as such early-stage prevention, since several studies highlight the importance of the entire microbial communities. Especially the beneficial members are known to be important for airway health and in preventing potential pathogens from causing excessive inflammation. In order to study these complex bacterial interactions in the CF host, more sophisticated models that better represent the in vivo conditions are needed. In this project, I aim to develop a CF interaction model to study these complex interactions by making use of a CF bronchoalveolar epithelial cell line and immune cell line. The interaction of both beneficial microbiome members and CF pathogens will be studied within the model, in terms of epithelial barrier stability, inflammatory cytokine and mucin expression, and cytotoxicity. This model can aid the development of microbiome therapies for the airways.

Researcher(s)

• Promoter: De Boeck Ilke

Research team(s)

• Laboratory of Applied Microbiology and Biotechnology (LAMB)

Project type(s)

• Research Project

Abstract

In an era marked by escalating concerns over antibiotic and antimycotic resistance, the need to explore unconventional sources of antimicrobial agents has become increasingly urgent. The emergence of antibiotic-resistant pathogens challenges the efficacy of traditional antibiotics, thereby causing serious global public health risks and a worldwide pandemic. In this context, lactobacilli, traditionally renowned for their probiotic properties, have recently emerged as a promising source of novel antibiotics. These lactic acid bacteria, abundant in various natural habitats including the human vagina and fermented foods, present a unique opportunity for the discovery of antimicrobial compounds that could potentially address the growing antibiotic resistance crisis. This research project aims to elevate recent discoveries regarding potential antibiotic production, including a novel type of bacteriocins, by lactobacilli from the host laboratory to a higher Technology Readiness Level (TRL). Our objectives include purifying and characterizing these compounds by assessing their antimicrobial efficacy against key pathogens, including yeasts like Candida albicans and ESKAPE pathogens and elucidate their mode of action. Hereto, we will assess their safety and efficacy in in vivo models and initiate the development of a (multispecies) bacterial formulation that can be used in future studies. The ultimate goal is to amass a robust dataset that can attract industrial partners for future endeavors aimed at clinical applications. Through innovative approaches, we aspire to unveil and harness the untapped antimicrobial potential of lactobacilli, providing a ray of hope in our ongoing battle against antibiotic resistance.

Researcher(s)

• Promoter: Lebeer Sarah

Research team(s)

• Laboratory of Applied Microbiology and Biotechnology (LAMB)

Project website

Project type(s)

• Research Project

Abstract

Space agencies are developing regenerative life support systems that provide air, water, and staple foods through hydroponic cultivation of a limited number of plants using crew waste as fertilizer, but these, mostly vegan, diets lack a number of essential nutrients found in a balanced diet. The aim of this project is to develop sustainable microbial-based food supplements for space travelers on long-duration space missions to the Moon and Mars. We will research and select suitable microbial-based food supplements, providing essential nutrients and vitamins to maintain human health and wellbeing, and still be active under stressful space conditions, including chronic exposure to reduced gravity and cosmic radiation. The growth and nutritional content of the microbial products and their safety and efficacy for human consumption in space will be evaluated, also by using reduced gravity simulators and space radiation analogs. In addition, it will be explored how on-site substrates (e.g. CO2 gas, regolith, etc.) could be used. The final outcome of the project will be a set of microbial strains or products that can be used as a reliable supplement to complete a space diet, improving the viability of human colonies on celestial bodies, and a first step towards a concept on how such a DIY production payload could look like.

Researcher(s)

• Promoter: Lebeer Sarah
• Co-promoter: Spacova Irina
• Fellow: Ellena Gabriele

Research team(s)

• Laboratory of Applied Microbiology and Biotechnology (LAMB)

Project type(s)

• Research Project

Abstract

Our economy is undergoing a complete transition from the current fossil-based to a sustainable biobased economy as a solution to the large societal and economic challenges. This transition creates a strong need for new technologies to convert renewable resources into a broad range of bioproducts, biomaterials and bioenergy. Industrial biotechnology, driven by metabolic engineering and synthetic biology, has been identified as a key enabling technology in the building process of libraries of potential microbial cell factories (MCFs) for producing such bioproducts. However, the transformation of wild type microorganisms into efficient, productive and robust MCFs remains an ennobled trial and error process. To this end, evolutionary biotechnology has attracted attention in recent years: adaptive laboratory evolution (ALE) is combined with high throughput screening methods, to generate and screen a massively diverse set of phenotypes and variants. In this project, we want to accelerate the industrial timeframe of traditional ALE approaches and apply an innovative and accelerated ALE to the non-model organism Lactobacillus casei for defined production of chitinpentaose. These molecules have a vast repertoire of application possibilities in sectors such as pharma, food, feed and cosmetics. Industry would greatly benefit from a probiotic chitooligosaccharides production system, starting from renewable resources, taking into account downstream processing and regulation costs.

Researcher(s)

• Promoter: Lebeer Sarah

Research team(s)

• Laboratory of Applied Microbiology and Biotechnology (LAMB)

Project type(s)

• Research Project

Abstract

Primary crop production is facing serious challenges with respect to climate change, sustainability, food security and socio-economic profitability. With an average yield loss of 23%, plant diseases and pests are an important threat to global food security. Chemical plant protection products (PPPs) are widely used to control diseases and pests. Due to their environmental impact and the resistance development of pathogens and pests against several PPPs, their application becomes more and more restricted. The European Farm to Fork strategy envisages to reduce the overall use and risk of chemical PPPs with 50% by 2030. To achieve this ambitious goal, alternative and highly effective management strategies, based on innovative technologies are needed. The SynBioS consortium aims to develop an innovative concept of synergy, where biocontrol technologies with different modes of action are being combined. To target insects, we will develop a root-associated microbe based approach to enhance plant resistance, and an indirect approach based on phages, targeting bacterial symbionts of the insects. To target fungi and bacteria, SynBioS will explore the composition and functionalities of the phyllosphere microbiome and use this data to develop a synthetic microbial community specifically tailored to tackle diseases. The different approaches will be combined and evaluated for potential synergies. Finally, to strongly increase the valorization potential of the SynBioS results, we will analyze the social acceptability and economic feasibility of the innovative biocontrol strategies. The SynBioS project will focus on strawberry as a first proof-of-concept and against its most important airborne diseases and pests. However, we expect that the groundbreaking technology-driven toolbox, developed by the SynBioS consortium, can be extrapolated to other crop production systems and will lead to a breakthrough in the efficacy and adoption rates of biological control.

Researcher(s)

• Promoter: Lebeer Sarah

Research team(s)

• Laboratory of Applied Microbiology and Biotechnology (LAMB)

Project type(s)

• Research Project

Abstract

Female specific health conditions are underrepresented in research. The taboo felt by women to talk about intimate wellbeing is fed by this gender gap in scientific knowledge. This project aims to meet these needs by studying one of the most prevalent female-specific infections, vulvovaginal candidiasis (VVC), and paving the way towards its efficient diagnosis and treatment. About 70% of women worldwide suffer from vaginal candidiasis at least once in their life. An episode of this fungal infection is accompanied by a burning sensation, pain, and a reduced mental wellbeing. Some women (about 5%) encounter such infectionsat least four times a year, referring to recurrent(R) VVC. The design of efficient diagnostic and therapeutic strategies for (R)VVC is hindered by a knowledge gap surrounding vaginal health. To meet the absolute need for more information, this project will characterize the role of the microbiome, metabolome, immune system, and pathogen characteristics in (R)VVC. To this end, a large sampling platform of women with/without VVC will be established in this project. We will identify the most important and clinically relevant micro-organisms, metabolites, and immune factors in VVC pathogenesis. VVC models will be developed and optimized, which will be used to validate the causality of the correlations identified in the cohort. Identified correlations will be proposed as biomarkers, and microbes, metabolites, and combinations, which effectively lower pathogenicity of Candida species, will be further investigated for therapeutic potential. State-of-the-art tools and know how in the consortium will allow us to unravel the involved molecular pathways and elucidate how these can be exploited to optimize therapeutic efficacy. Finally, the knowledge gathered in this project will be used to improve literacy of women on VVC using platforms established by the consortium as well as novel tools to be developed in this project.

Researcher(s)

• Promoter: Lebeer Sarah

Research team(s)

• Laboratory of Applied Microbiology and Biotechnology (LAMB)

Project type(s)

• Research Project

Abstract

Mobile genetic elements (MGEs) are genetic elements that can move around within genomes or between cells. It is known that MGEs play a crucial role in prokaryotic ecology and evolution. However, due to limitations of current MGE detection tools in prokaryotic genomes, the full size and diversity of the prokaryotic mobilome is unknown, as well as the extent to which MGEs interact. In addition, current knowledge on the host range of various types of MGEs is limited. This project aims to explore the full mobilome of the important orders Lactobacillales and Enterobacterales, two taxa that are densely sampled in terms of the number of strains with sequenced genomes in public databases. First, a novel tool will be developed that can predict the full mobilome of a set of genomes in a database-independent manner, based on comparative genomics. Second, this tool, as well as existing MGE prediction tools, will be applied to both taxa. The predicted MGEs will be clustered, and presence/absence correlations between the resulting clusters will be determined to assess interactions between the elements. Third, the co-evolutionary history of MGE clusters and their host genomes will be explored and ancestral MGE transfer events inferred. Finally, the host clades of the MGEs will be predicted and validated through CRISPR spacer matching. Together, these analyses will yield new insights into the "dark matter" of the prokaryotic mobilome.

Researcher(s)

• Promoter: Lebeer Sarah
• Fellow: Wittouck Stijn

Research team(s)

• Laboratory of Applied Microbiology and Biotechnology (LAMB)

Project type(s)

• Research Project

Abstract

In this project, we will study the vaginal microbiome and the microbiome of endometrium biopts via amplicon sequencing 16S via standard pipelines of the host lab for wetlab and in silico analyses. The partner is the main coordinator if this project. We provide a service.

Researcher(s)

• Promoter: Lebeer Sarah

Research team(s)

• Laboratory of Applied Microbiology and Biotechnology (LAMB)

Project type(s)

• Research Project

Abstract

Women's health is receiving increased attention, but science is still not filling society's needs when it comes to vaginal health. For instance, in the last 40 years, no major breakthroughs have been made to manage bladder and vaginal infections. One way in setting a societally relevant research agenda is actively involving citizens in scientific dialogues. We have founded the Isala project as a citizen-science project to significantly advance research, diagnostics and therapeutics for the vaginal microbiome. In the first pioneering phase of the project, more than 5500 women have provided intimate samples and data; proposed research objectives and survey questions; and helped disseminate and interpret results. Thanks to the enthusiasm of the Belgian citizens participating and cocreating the research questions, we have built the largest citizen-science project in the world on the vaginal microbiome. And we are still expanding! Now, we want to expand this cohort in Belgium and across the world, to jointly taboos on women's health, increase scientific literacy and provide new insights in associations of lifestyle with the vaginal microbiome and work on and tangible solutions such as microbiome-modulating strategies.

Researcher(s)

• Promoter: Lebeer Sarah

Research team(s)

• Laboratory of Applied Microbiology and Biotechnology (LAMB)

Project type(s)

• Research Project

Abstract

In this project, we will explore the process of fruit fermentation via lactic acid bacteria and yeast to have a safe, tasty product with an enhanced shelf-life of use in bakeries. This project is confidential and no details can be disclosed.

Researcher(s)

• Promoter: Lebeer Sarah

Research team(s)

• Laboratory of Applied Microbiology and Biotechnology (LAMB)

Project type(s)

• Research Project

Abstract

The aim of this project is to gain a better overall understanding of the relationship between the respiratory microbiota (upper and lower) and the intestine in pigs, which will provide a deeper insight into both composition and functionality of the microbes present. These insights will reveal genetic characteristics of pathogenic bacteria (such as virulence factors). results, but the presence of useful bacteria will also be visualized, which can be used for the optimization of existing workflows and the development of potential probiotics.

Researcher(s)

• Promoter: Lebeer Sarah

Research team(s)

• Laboratory of Applied Microbiology and Biotechnology (LAMB)

Project type(s)

• Research Project

Abstract

The phytopathogenic fungus, Botrytis cinerea, is the most common reason for fruit rejection in small fruit crops such as the strawberry plant. To get rid of this fungus, chemical fungicides are still the most popular worldwide. Due to increased resistance, growing environmental awareness, continued consumer demand for fewer pesticide residues and more stringent policies in many countries, more and more research is being devoted to sustainable alternatives fitting within the framework of integrated pest management. Within this project, biocontrol using lactic acid bacteria is studied as an alternative. Lactic acid bacteria are well known for their protective properties within food applications, but their role on the plant and their potential as a biocontrol organism on the phyllosphere have only been investigated to a limited extent. To avoid inconsistent field performance, a common problem in biocontrol, candidates will be screened for their potential to survive and grow on the phyllosphere. We will focus on the entomovectoring system as the approach to applying these potential biocontrol agents. In this system, a vector, Bombus terrestris, will disseminate an optimized formulation of lactic acid bacteria directly to the strawberry flowers. In this way, pollination and crop protection are done at the same time and efficient delivery towards the target location is guaranteed.

Researcher(s)

• Promoter: Lebeer Sarah
• Co-promoter: Kiekens Filip
• Fellow: Temmermans Jari

Research team(s)

• Laboratory of Applied Microbiology and Biotechnology (LAMB)

Project type(s)

• Research Project

Abstract

The microbiota of the upper respiratory tract (URT) is emerging as a gatekeeper to respiratory health, but it is currently underexplored at the functional level compared to other body sites. URT diseases such as otitis media (OM) form leading causes for antibiotic prescription, while the functional role of bacteria in the disease pathology is still not clear. Consequently, new insights into the functional biology and microbial ecology of OM as a microbial disease are needed to design novel therapeutic strategies. Microbiome sequencing of the URT revealed Streptococcus salivarius as one of the primary colonizers of the oral cavity shortly after birth. It is also significantly more abundant in the nasopharynx of healthy children compared to children with chronic OM. Endogenous beneficial bacteria can indeed play a pivotal role in URT health through inhibition of respiratory pathogens and immunomodulation. As a key beneficial commensal, specific strains of S. salivarius could have high potential as URT probiotics. These strains can produce secreted secondary metabolites with bacteriostatic or bactericidal activity, but their role in probiotic effects is currently underexplored. This project will focus on exploring the metabolic properties and functional potential of S. salivarius isolates, which will be evaluated through dedicated in vitro culturing systems, phenotypic screening assays and comparative genomics, combined with an innovative proof-of-concept study in humans.

Researcher(s)

• Promoter: Lebeer Sarah
• Co-promoter: Boudewyns An
• Co-promoter: Spacova Irina
• Co-promoter: Vanderveken Olivier
• Fellow: Van Malderen Joke

Research team(s)

• Laboratory of Applied Microbiology and Biotechnology (LAMB)

Project type(s)

• Research Project

Abstract

Fermented foods are defined as foods made through desired microbial growth and enzymatic conversion of food components. Despite being widely consumed, only a few vegetable fermentations (e.g. kimchi) have been extensively studied, but others remain largely understudied. These vegetable fermentations are mostly spontaneous and could benefit from a dedicated starter culture to improve safety, flavor, texture, and health potential, such as production of vitamins. This project will therefore focus on collecting a wide range of fermented vegetable samples through citizen science projects both in Belgium and USA. Species level community dynamics will be explored to understand the ecology of lactic acid bacteria (LAB) in these man-made environments. LAB will be isolated as potential starter cultures. Traditionally, starter culture selection relies mostly on labor intensive trial and error screening but in our project, we propose the use of genome-scale metabolic models (GEMs) for rapid screening of metabolic potential. Starter cultures will be fully characterized both in silico using GEMs and in vitro phenotypic characterization. Based on these results, starter cultures will be metabolically engineered for the increased expression of target metabolites to improve texture, flavor and health potential. This project will result in 5 optimized functional starter cultures together with a metabolic engineering pipeline for future starter cultures.

Researcher(s)

• Promoter: Lebeer Sarah
• Fellow: Van Beeck Wannes

Research team(s)

• Laboratory of Applied Microbiology and Biotechnology (LAMB)

Project type(s)

• Research Project

Abstract

The aim of this PhD project is to determine the radioprotective mode of action of biotic food supplements including LGG and Limnospira sp.. First (WP1), we will implement the newly GuMI platform using human gut derived organoids and CRC tumoroids, in a radiotherapy relevant setup which has never been done before, then (WP2) to investigate barrier protective and immunomodulatory mechanisms of action of LGG and Limnospira sp. either individually and in a symbiotic combination, and in parallel (WP3) to continue the search for new radioprotective agents of natural origin taking advantage of the higher screening throughput and human physiological applicability provided by the GuMI platform compared to mouse studies. This could also include the use of FMT, as a more holistic gut microbiome-based therapy.

Researcher(s)

• Promoter: Lebeer Sarah

Research team(s)

• Laboratory of Applied Microbiology and Biotechnology (LAMB)

Project type(s)

• Research Project

Abstract

ODORETION researches and develops technology paths to remediate and prevent malodors in bedrooms, bathrooms and toilets. A research platform with modular methodologies will form a solid basis for identifying the most effective biological and chemical technologies. On top of that, ODORETION aims to be more sustainable than the typically used toxic and less environmentally friendly strategies.

Researcher(s)

• Promoter: Lebeer Sarah

Research team(s)

• Laboratory of Applied Microbiology and Biotechnology (LAMB)

Project type(s)

• Research Project

Abstract

In this project, together with partners at KU Leuven, we want to investigate the vaginal microbiome in women with iatrogenic menopause caused by breast cancer treatment and its association with vaginal health and sexuality (www.volupta.be).

Researcher(s)

• Promoter: Lebeer Sarah

Research team(s)

• Laboratory of Applied Microbiology and Biotechnology (LAMB)

Project type(s)

• Research Project

Abstract

Speaking openly about vaginal health is taboo in Peru, and public attention to intimate female care has been neglected for decades. For instance, during the present pandemic, several primary health care centers shut down gynaecological consultations, affecting women suffering from vaginal infections. With the current Laura 2.0 project, we aim to create a national (in Peru) and international research network investigating on vaginal health by actively engaging several key stakeholders from society and academia. Higher education institutions (HEIs) will play a key role in achieving Laura 2.0 aim. Universidad Nacional de la Amazonia Peruana (UNAP) and Universidad Nacional San Agustín de Arequipa (UNSA) are the prominent universities in the Peruvian Amazon and the Highlands regions, respectively. Both HEIs are strengthening their key roles in developing their regions by consolidating their research capacity. The current project will strengthen the national (UNAP-UNSA-UPCH) and international (local partners and UAntwerp) collaboration by actively developing research capacities in a multidisciplinary approach. More importantly involving (for the first time in Peru), citizens (women) in science, via a citizen science project inspired by the Belgian Isala project (https://isala.be/en).

Researcher(s)

• Promoter: Lebeer Sarah
• Co-promoter: Brusselaers Nele
• Co-promoter: Condori Sandra
• Co-promoter: Verhoeven Veronique

Research team(s)

• Laboratory of Applied Microbiology and Biotechnology (LAMB)

Project type(s)

• Research Project

Abstract

COOLSCHOOLS is a transdisciplinary applied urban research project that examines the transformative potential of nature-based solutions (NBS) to support the creation of climate shelters in European school environments. We assess how nature-based climate shelters can drive social-ecological transformations towards urban sustainability, climate resilience, social justice, and quality education at multiple urban scales (from schools to metropolitan region) and translate them into practical building capacity for school communities and beyond. Building on pioneering pilot NBS projects of school transformation in Barcelona, Brussels, Paris, and Rotterdam, COOLSCHOOLS unravels the specificities of each context and finds common patterns related to climate shelters transformation capacities, focusing on marginalized groups. Through participatory and co-creation methodologies, we propose an interdisciplinary approach that combines natural, bio-medical, social, and education sciences. To further promote a holistic approach to school climate shelters transformation capacities, we will actively disseminate the pilots' best practice and key learnings among city governments, urban planners, companies, school communities and other relevant stakeholders. The consortium's cross-sectoral composition ensures active multi-stakeholder involvement through an urban living lab and other co-engagement actions, that are planned to boost reflection and learning, and the wider use of COOLSCHOOLS outputs.

Researcher(s)

• Promoter: Casas Ruiz Lidia

Research team(s)

• Social Epidemiology & Health Policy (SEHPO)
• Laboratory of Applied Microbiology and Biotechnology (LAMB)

Project type(s)

• Research Project

Abstract

Lactobacilli are among the best documented beneficial bacteria. Humans are unique animals having a reproductive tract dominated by lactobacilli. In the female reproductive tract, Lactobacillus taxa normally dominate this habitat under healthy conditions, with numbers up to 90-100%. However, there exists a major knowledge gap on why this is the case. The biodiversity, dynamics and evolutionary history of vaginal lactobacilli are largely underexplored. In this project, we aim to follow an innovative sequencing and Citizen Science approach to genetically and functionally characterize vaginal lactobacilli (isala.be). This will include shallow shotgun, whole genome and innovative culturomics and characterization strategies. Specific attention will be given to their adaptation to the vagina and antimicrobial properties.

Researcher(s)

• Promoter: Lebeer Sarah

Research team(s)

• Laboratory of Applied Microbiology and Biotechnology (LAMB)

Project type(s)

• Research Project

Abstract

The urogenital microbiome is a crucial microbiome for human health and reproduction. Lifestyle and hygiene practices are suggested to have a strong influence on the urogenital microbiome. For instance, humans are the only animals that wear clothes, and certain underwear fabrics have been correlated with higher risk of urogenital disease. However, the causal relationship between urogenital health and underwear fabrics is underexplored, especially regarding how underwear could influence the urogenital microbiome. In this project, we first aim to correlate the use of specific underwear fabrics with vaginal health and microbiome, exploring the dataset generated by the host lab from more than 3300 Isala study participants. In parallel, a microbiological in vitro platform will be designed for the evaluation of microbiome-friendly characteristics of (underwear) fabrics through the use of defined microbial communities. Subsequently, a key part of the project will consist of a large-scale study that will explore in vivo interactions between specific underwear fabrics, the vaginal, vulvar and skin microbiome and urogenital health. The ultimate application aim is to better understand how underwear fabrics can affect female health, and implement microbiome-friendly underwear through future collaborations between the academic, health and textile sectors.

Researcher(s)

• Promoter: Lebeer Sarah
• Co-promoter: Spacova Irina
• Co-promoter: Verhoeven Veronique
• Fellow: Vander Donck Leonore

Research team(s)

• Laboratory of Applied Microbiology and Biotechnology (LAMB)

Project type(s)

• Research Project

Abstract

Vitamin producing microorganisms are emerging as a natural, cost-effective and sustainable alternative to chemical vitamin production. To date, they have mainly been explored in the gut and fermented food, however, recently, the host group isolated several vaginal lactobacilli capable of vitamin B2 (over)production. Lactobacilli have a long history of safe use and are highly suitable for application as probiotics or for biofortification of foods, yet they are generally still applied as 'black boxes', without full understanding of the genes and molecules that drive their beneficial action. In this project, we will perform in silico and in vitro functional screening of the host group's large biobank of more than 1000 human bacterial isolates with the innovative goal to identify and characterize vitamin producing lactobacilli from untapped non-gut body niches (vagina, upper respiratory tract), and fermented foods. Next, to better understand and enhance the vitamin producing capacity of lactobacilli, untargeted and targeted genetic modification strategies will be implemented. A specific unique and challenging focus will be on the functionalization of the novel CRISPR-Cas9 based tool 'Prime editing' in lactobacilli for targeted genetic alterations leading to vitamin overproduction. Overproduction phenotypes, naturally isolated or resulting from genetic engineering approaches, can then be used in food/feed, as supplements and in human therapeutic applications.

Researcher(s)

• Promoter: Lebeer Sarah
• Co-promoter: Spacova Irina
• Fellow: Dricot Caroline

Research team(s)

• Laboratory of Applied Microbiology and Biotechnology (LAMB)

Project type(s)

• Research Project

Abstract

Up to 75% of females worldwide encounter at least one episode of vulvovaginal candidiasis (VVC) in their lifetime and 5%-10% of them suffers from recurrent infections (RVVC). Globally, RVVC is estimated to target 150 million women a year by 2030, leading to universal healthcare related and economic losses. Current treatment of (R)VVC is insufficient and resistance occurs frequently. Therefore, the development of additional, effective therapy strategies has become urgent. In this project, we will investigate the treatment of (R)VVC with probiotics based on S. cerevisiae alone and in combination with Lactobacillus spp., in in vitro and in vivo setups. Additionally, we will generate an overview of the vaginal mycobiome of the Belgian population. This overview will allow us to compare the healthy and (R)VVC-linked microbiome, generating insight into the relationships between microorganisms present in this niche. This could highlight microorganisms that could have probiotic capacities against Candida species.

Researcher(s)

• Promoter: Lebeer Sarah

Research team(s)

• Laboratory of Applied Microbiology and Biotechnology (LAMB)

Project type(s)

• Research Project

Abstract

The upper respiratory tract (URT) is a key habitat of the human microbiome, but it is currently underexplored compared to other body sites, especially at the functional level. URT diseases such as chronic rhinosinusitis (CRS) form leading causes for antibiotic prescription, while the functional role of bacteria in the disease pathology is still not clear. As such, CRS is a microbial disease needing new insights in functional biology and microbial ecology to design novel therapeutic strategies. Based on microbiome sequencing of the URT, the underexplored lactic acid bacterium Dolosigranulum pigrum is associated with URT health, highlighting its potential as URT probiotic. Nevertheless, fundamental and molecular research is lacking on its beneficial mechanisms of action, and on its ecological and adaptation mechanisms in the human nasal cavity. This project will therefore focus on exploring the biology and metabolic properties of D. pigrum strains isolated from healthy URT samples, using comparative genomics, phenotypic screening assays and fluorescent microscopy techniques. In addition, the barrier-enhancing and anti-inflammatory properties of D. pigrum isolates will be evaluated in complex in vitro cell culture systems. In parallel, molecular biology tools will be used for further molecular characterization of the isolated strains' mechanisms of action. Finally, the most promising D. pigrum strains will be evaluated in murine models relevant for CRS.

Researcher(s)

• Promoter: Lebeer Sarah
• Co-promoter: Vanderveken Olivier
• Fellow: De Boeck Ilke

Research team(s)

• Laboratory of Applied Microbiology and Biotechnology (LAMB)

Project type(s)

• Research Project

Abstract

The effects of green spaces on respiratory health are unclear. Potential reasons for inconsistencies across studies are the study design (cross-sectional or short follow-ups), exposure measurement being limited to the residence, and limited consideration of potential mediators and modifiers (e.g. oxidative stress, maternal stress during pregnancy). Therefore, we propose a longitudinal study investigating the association of early life exposure to green spaces with respiratory outcomes up to adulthood. This project is based on a recently granted FWO project (see application). The project will use the PIPO birth cohort, containing information from birth to adolescence on the development of allergies, respiratory symptoms, lung function, anthropometrics, and allergic sensitization. This project will add an early adulthood (20-24y) follow-up to the PIPO-data. Addresses (residences, day care/school/work) will be linked to measures of land use and greenness (Corine Land Cover, NDVI, etc.), and air pollutants. Further, measures of oxidative stress (9y) will be done using existing samples. Using that data, we will consider mediation effects of air pollution, body mass index, and oxidative stress during childhood. Direct and indirect effects of early life exposure to green spaces will be assessed through mediation analyses.

Researcher(s)

• Promoter: Casas Ruiz Lidia

Research team(s)

• Laboratory of Applied Microbiology and Biotechnology (LAMB)
• Social Epidemiology & Health Policy (SEHPO)

Project type(s)

• Research Project

Abstract

Atopic dermatitis (AD) is a chronic inflammatory disease of the skin that occurs in about 20% of children and 3% of adults in Western countries. AD is characterized by acute flare-ups of itchy eczematous lesions and dry skin. The etiology of AD is complex, the appearance and course of the disease are influenced by both genetic and immunological mechanisms and environmental factors, such as pathogenic microorganisms. In this project,, we aim to characterize the microbiome of children with AD and investigate the impact of a topical therapeutic strategy with well selected lactobacilli.

Researcher(s)

• Promoter: Lebeer Sarah
• Co-promoter: Hagendorens Margo
• Fellow: Delanghe Lize

Research team(s)

• Laboratory of Applied Microbiology and Biotechnology (LAMB)

Project type(s)

• Research Project

Abstract

Synthetic biology is a new discipline that allows designing and creating novel, completely man-made biological systems such as metabolic pathways. The innovative technology is a game-changer for the sustainable production of pharmaceuticals, biofuels, enzymes, aroma compounds and bioplastics. The synthetic systems are often implemented in E. coli or yeast cells because the biotechnological toolbox for these organisms is readily available. However, these microbes are often not optimally suited for industrial or medical applications. This project therefore aims to develop a novel toolbox that allows the ethical exploitation of superior non-standard microbes. The project will not only yield an important breakthrough for the efficiency and possibilities of synthetic biology, but also constitutes a research consortium of a team of young and ambitious scientists that will serve as a strategic hub for the further development of synthetic biology in Flanders, thereby helping to maintain its leading position in biotech.

Researcher(s)

• Promoter: Lebeer Sarah
• Co-promoter: Hens Kristien

Research team(s)

• Laboratory of Applied Microbiology and Biotechnology (LAMB)

Project type(s)

• Research Project

Abstract

The effects of green spaces on allergy and respiratory health are unclear. Potential reasons for inconsistencies across studies are the study design (cross-sectional or short follow-ups), exposure measurement being limited to the residence, and limited consideration of potential mediators and modifiers (e.g. oxidative stress, maternal stress during pregnancy). Therefore, we propose a longitudinal study investigating the association of early life exposure to green spaces with respiratory and allergic outcomes up to adulthood. The project will use the PIPO birth cohort, containing information on early life exposure to residential green spaces, and the development of allergies, respiratory symptoms, lung function anthropometrics, and allergic sensitization from birth to adulthood. This project will add an early adulthood (20-24y) follow-up to the PIPO-data. Addresses (residences, day care/school/work) will be linked to measures of land use and greenness (Corine Land Cover, NDVI, etc.), and air pollutants. Further, measures of oxidative stress (9y) and cortisol in newborn hair (maternal stress) will be done using existing samples. Using that data, we will consider mediation effects of air pollution, body mass index, maternal stress during pregnancy, and oxidative stress during childhood. Direct and indirect effects of early life exposure to green spaces will be assessed through mediation analyses, and effect modification by maternal stress during pregnancy will be tested.

Researcher(s)

• Promoter: Casas Ruiz Lidia

Research team(s)

• Laboratory of Applied Microbiology and Biotechnology (LAMB)
• Social Epidemiology & Health Policy (SEHPO)

Project type(s)

• Research Project

Abstract

Often a microbiome modification with a "beneficial" microbe does not yield the desired results. This illustrates the need of better tools to study the ecology and evolution of microbiomes, and the effects of artificial modifications to these microbiomes. This project proposes the innovative approach of combining synthetic microbial communities with shallow shotgun metagenomics to gain unprecedented understanding in microbial communities in general. The proposed approach will be developed for a phyllosphere model and used for experimental microbial evolution of whole communities. Successive passaging experiments will be set up where synthetic phyllosphere communities will be moved from one generation of host plant to the next. The results of these experiments will lead to new insights in the ecology and evolution of phyllosphere communities. This project aims at setting up this approach to be more widely useable for testing existing and developing new evolutionary theories. Finally, the impact of the addition of a "beneficial" microbial strain to the phyllosphere model will be studied at the level of the microbiome ecology and evolution, allowing novel insight in long-term effects of artificial modifications of our microbial environment.

Researcher(s)

• Promoter: Lebeer Sarah
• Fellow: Smets Wenke

Research team(s)

• Laboratory of Applied Microbiology and Biotechnology (LAMB)

Project type(s)

• Research Project

Abstract

Lactobacillus bacteria have a strong, but underexplored potential as sustainable bio-based solutions for many food and health-related problems. Since Nobel-laureate Eli Metchnikoff hypothesized that lactic acid bacteria can promote human health in the gut, the research on lactobacilli and probiotics has mainly focused on the human gut and fermented dairy foods. However, a major knowledge gap exists on the beneficial potential of Lactobacillus species in other human body sites (vagina, skin, upper respiratory tract), animals (e.g. chickens, honey bees), plants, crops, and even on abiotic surfaces. In addition, lactobacilli play a key role in many plant- and vegetable-based fermentations, where they promote the shelf life and nutritional value of food and feed. Yet, why and how Lactobacillus species can be beneficial in such a wide variety of niches is currently underexplored. Therefore, the core aim of this project is a systematic and integrated analysis of the evolutionary history, ecology, and beneficial functions of Lactobacillus species. I propose an unconventional approach situated at the intersections of molecular microbiology (focusing on a single microbe), molecular ecology (focusing on microbial communities) and comparative genomics with an evolutionary perspective on niche adaptation of lactobacilli. By looking deeper into Lactobacillus biology, a paradigm shift can be made moving from a classical ad hoc base to a unique knowledge-based framework for strain selection and analysis of fitness and performance.

Researcher(s)

• Promoter: Lebeer Sarah

Research team(s)

• Laboratory of Applied Microbiology and Biotechnology (LAMB)

Project type(s)

• Research Project

Abstract

A steady increase in chronic inflammatory diseases can be observed in regions with a high degree of industrialization and urbanization since World War II. The pro-inflammatory capacity of ambient air particulate matter and other air pollutants seems an important factor in the pathogenesis of these diseases, but the underlying mechanisms are not well understood. This project aims to generate more insights in the (micro)biology of air pollution by application of techniques from the fields of molecular microbiology and immunology to investigate the presence of micro-organisms and their endotoxins in particulate matter (PM) and to characterize the pro-inflammatory capacity of PM in detail.

Researcher(s)

• Promoter: Lebeer Sarah
• Fellow: Lebeer Sarah

Research team(s)

• Laboratory of Applied Microbiology and Biotechnology (LAMB)

Project type(s)

• Research Project

Abstract

Primary crop production is facing serious challenges with respect to climate change, sustainability, food security and socio-economic profitability. With an average yield loss of 23%, plant diseases and pests are an important threat to global food security. Chemical plant protection products (PPPs) are widely used to control diseases and pests. Due to their environmental impact and the resistance development of pathogens and pests against several PPPs, their application becomes more and more restricted. The European Farm to Fork strategy envisions to reduce the overall use and risk of chemical PPPs with 50% by 2030. Biocontrol applications could be valuable alternatives to overcome the disadvantages of these chemical PPPs. Currently, not many bacterial-based PPP strategies exist and the current bacterial strategies are largely focusing on spore-forming bacilli. Here we propose to explore the potential of lactic acid bacteria. If they show activity in the lab against major pathogens, we will explore their most suitable formulation and activity in more relevant conditions.

Researcher(s)

• Promoter: Lebeer Sarah

Research team(s)

• Laboratory of Applied Microbiology and Biotechnology (LAMB)

Project type(s)

• Research Project

Abstract

The nasal epithelium forms the first line of defense against environmental insults. Damage to epithelial structure and function, is involved in the pathology of chronic rhinosinusitis with nasal polyps (CRSwNP). Bitter (T2R) and sweet (T1R) taste receptors are upper airway sensors that detect and induce a rapid immune response against secreted bacterial ligands. Activation of T2Rs on nasal epithelium results in rapid calcium release that stimulates the secretion of antimicrobial compounds and production of nitric oxide, consequently killing the bacteria and increasing ciliary beating. Activation of T1R antagonizes the host's T2R mediated immune response. Moreover, T1R agonists increase bacterial survival and propagation. In line with this, we have previously demonstrated that patients with CRSwNP have an increased presence of pathogenic bacteria and a decrease in beneficial lactic acid bacteria, which are able to modulate barrier homeostasis. Unfortunately, limited studies focus on the relationship between the nasal microbiome and taste receptor function in CRSwNP patients. As such, in this project we will investigate the effect of bacterial ligands, produced by the nasal microbiome, on taste receptor function in CRSwNP.

Researcher(s)

• Promoter: Lebeer Sarah

Research team(s)

• Laboratory of Applied Microbiology and Biotechnology (LAMB)

Project type(s)

• Research Project

Abstract

The main objective of this project is to acquire new biological and genetic insights on the application of microorganisms as bioremediation of PAHs in air pollution. Such new insights will lead to a scientific underpinning of a new air purification application based on the spread of benign bacteria in the environment.

Researcher(s)

• Promoter: Lebeer Sarah
• Fellow: Dekeukeleire Max

Research team(s)

• Laboratory of Applied Microbiology and Biotechnology (LAMB)

Project type(s)

• Research Project