Mapping the Peruvian vaginal microbiota and linking it to increased awareness and capacity building. 01/01/2021 - 31/12/2021

Abstract

The human microbiota is composed of a vast number of microorganisms inhabiting different body sites, especially the skin, gut, vagina. For women, the bacteria inhabiting the vaginal tract, specifically Lactobacillus spp. (mainly by L. crispatus, L. iners, L. jensenii, L. gasseri) play a key role in sexual and reproductive health. For instance, a disruption of the vaginal microbiota is associated with a variety of pathogenic disorders, such as bacterial vaginosis (BV), highly prevalent in Peru (estimated to range between 10-37%). Affected women are at increased risk of acquiring more serious infectious agents such as HIV, Chlamydia, Trichomonas, Neisseria. Other complications of BV include preterm premature rupture of membranes and neonatal sepsis. Previously, a healthy vaginal microbiota composition has been defined when high numbers of lactic acid producing lactobacilli were present based on microscopy or culture-based approaches, including pH measurements. Nowadays with the development of culture-independent approaches such as next-generation sequencing (NGS), we know that the vaginal microbiota is not only composed of Lactobacillus species but also of a diverse group of strictly anaerobic bacteria. However, while several of these anaerobic bacteria appear to be associated to disorders such as BV, some might also be linked to health. This is at present not well understood. Based on studies on the gut microbiota, several factors have been described that can influence this microbiota composition, including dietary habits, health status, demographics, environmental factors, and ethnicity. For the vaginal microbiota, this area of research is still largely underexplored. Several studies indicate that ethnicity might also play a key role in shaping the vaginal microbiota. For example, Ravel et al. have observed that African American and Hispanic women have predominantly anaerobic bacteria compared to women from European ancestry (Lactobacillus-dominant). However, most vaginal microbiota studies have been focused on the "Western white woman" so far. Hence, the impact of ethnicity on the vaginal microbiota remains a critical research gap in this field. To overcome various knowledge gaps on the vaginal microbiota, our research group has recently set up a citizen science project named Isala to explore the female microbiota's stability and temporal dynamics in relation to different lifestyle factors and environmental conditions. We also explore the importance of various individual and social risk factors that can influence the "healthy" vaginal microbiota. While we were aiming to recruit 200 volunteers in Flanders at the start of the project in March 2020, we managed to enroll at least 5528 women due to immense success and large amounts of subscriptions (we even had to stop registrations). This massive response from women highlights the need that it is important to understand the vaginal microbiota better, how this microbiota is influenced, and its impact on health. In this present project proposal, we aim to implement the Isala project in Peru to radically increase our insights on the diversity of a "healthy" vaginal microbiota composition and the influence of ethnicity and other possible factors.

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Beneficial Lactobacillus interactions at the nasopharyngeal epithelium. 01/10/2013 - 30/09/2017

Abstract

The human body is occupied by a vast number of microorganisms, which are collectively called microbiota. They inhabit the skin, oronasopharyngeal cavity, genital tract and gastrointestinal tract. The microbiota present in each of the niches provides to the host a vast number of health effects, including inhibition of bacterial pathogenic colonization, stimulation of immune responses and promotion of immune regulation. Interest in the beneficial functions of the human microbiota has boomed within the last ten years, thanks to major advances in next generation sequencing technologies in so called 'metagenomic studies'. In this rather new 'microbiota field', the potential of nasal and pharyngeal probiotics is currently unexplored, while they hold great promise for multiple reasons. Among these, the facts that (i) upper respiratory tract infections, including acute otitis media, are the leading causes for the prescription of antibiotics in children and that (ii) the oronasopharyngeal cavity is quite accessible and generally populated by a less complex and less dense microbiota than the gut, form a major incentive for the proposed PhD project. In this study, fundamental questions underlying the potential of oronasopharyngeal application of probiotic lactobacilli will be studied. Hereto, a stepwise in vitro experimental design will be followed. The research questions that will be addressed include: (i) are lactobacilli tolerated by upper respiratory tract cells, (ii) can we select lactobacilli with inhibitory activity against typical bacterial respiratory pathogens, (iii) Do these lactobacilli also have potential to counteract aspects of the pro-inflammatory and oxidative activity of air pollution, (iv) which are the molecular mechanisms of probiotic action involved? To study potential modes of action, we will implement the construction and phenotypic analysis of dedicated knock-out mutants of Lactobacilli lacking putative probiotic factors. These in vitro experiments should deliver data for later in vivo animal studies and clinical trials.

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