Sarah Lebeer is a research professor at the Department of Bioscience Engineering of the University of Antwerp. She is heading the Laboratory for Applied Microbiology and Biotechnology. The major research topics within this lab are all driven by a passion for beneficial bacteria and microbiome research (www.lebeerlab.com). The team studies host-microbe interaction mechanisms to develop microbiological alternatives for antibiotics, such as probiotics and live biotherapeutic products to boost human, animal and plant health. In addition, the team aims to adopt citizen-science approaches in different research lines when there is a mutual interest and benefit for participants and scientists. In 2020, the team has launched their most recent citizen science project on women’s health and the vaginal microbe (isala.be/en), thanks to funding via an ERC Starting grant Lacto-Be.
The vaginal microbiome is crucial for women’s health and reproduction, but its ecology and determinants in the general population are still understudied, especially if you compare it to the booming field of the gut microbiome. It is the ambition of the Isala citizen-science consortium (https://isala.be/en) to overcome this knowledge, but also innovation gap, by combining a citizen science approach with vaginal microbiome research. In a first phase of the project, we mapped the vaginal microbiome of women in Belgium and analyzed more than 3300 samples, the largest collection in one lab at that time. This analysis showed that more than 75% of the Belgian women studied have a vagina dominated by Lactobacillus taxa. Especially Lactobacillus crispatus and Lactobacillus iners appear to be predominating, but the different species do not occur in discrete community state types. Compositional correlation network analysis validated with public data pointed at four main modules of interacting microbes: a Lactobacillus, Gardnerella-, Prevotella-, and Bacteroides-centred module. In the first module, Limosilactobacillus taxa are functionally connected to L. crispatus and Lactobacillus jensenii. This module is also positively associated with the luteal phase of the menstrual cycle and negatively with the number of vaginal complaints, while the Gardnerella-module is associated with discharge and increasing age. Contraceptives with oestrogen correlate with higher levels of the L. crispatus- and less of the Gardnerella-module, with the opposite found for a hormonal intrauterine device or having multiple partners. Surprisingly, mothers appeared to have lower relative abundance of the L. crispatus-module and more Bifidobacterium, Lactobacillus gasseri and Streptococcus. Other covariates such as BMI, menstrual pads and menstrual cups, smoking and dietary habits were also found to be associated with different parameters studied for microbial constellation composition (beta & alpha-diversity, individual taxa and modules). These data indicate that lifestyle interventions have potential to improve vaginal health when combined with dedicated therapies, but of course further in-depth follow-up and mechanistic research is still needed, such as several projects already initiated in our lab that will be introduced during this talk.
Recurrent urinary tract infection and estrogen shape the taxonomic ecology and function of the postmenopausal urogenital microbiome
Postmenopausal women are severely affected by recurrent urinary tract infection (rUTI). The urogenital microbiome is a key component of the urinary environment. However, changes in the urogenital microbiome underlying rUTI susceptibility are unknown. Here, we perform shotgun metagenomics and advanced culture on urine from a controlled cohort of postmenopausal women to identify urogenital microbiome compositional and function changes linked to rUTI susceptibility. We identify candidate taxonomic biomarkers of rUTI susceptibility in postmenopausal women and an enrichment of lactobacilli in postmenopausal women taking estrogen hormone therapy. We find robust correlations between Bifidobacterium and Lactobacillus and urinary estrogens in women without urinary tract infection (UTI) history. Functional analyses reveal distinct metabolic and antimicrobial resistance gene (ARG) signatures associated with rUTI. Importantly, we find that ARGs are enriched in the urogenital microbiomes of women with rUTI history independent of current UTI status. Our data suggest that rUTI and estrogen shape the urogenital microbiome in postmenopausal women.
Michael Neugent, Ashwani Kumar, Neha Hulyalkar, Kevin Lutz, Vivian Nguyen, Jorge Fuentes, Cong Zhang, Amber Nguyen, Belle Sharon, Amy Kuprasertkul, Amanda Arute, Tahmineh Ebrahimzadeh, Nitya Natesan, Chao Xing, Vladimir Shulaev, Oiwei Li, Philippe Zimmern, Kelli Palmer, Nicole Janell De Nisco
Presenting author affiliation: Department of Biological Sciences, The University of Texas at Dallas
Maternal and foetal outcomes among pregnant women with vaginal dysbiosis: a systematic review and meta-analysis
Bacterial vaginosis (BV) is the most common gynecological condition in women of reproductive age. BV affects women during pregnancy and could lead to maternal-foetal outcomes that can be fatal for mothers and newborns. The aim of this review is to identify the different maternal and foetal outcomes among pregnant women with BV encountered worldwide and to highlight their prevalence. We search worldwide published articles that have recorded the prevalence of maternal-foetal outcomes among pregnant women with BV in the database Embase, PubMed, Web of Science, and Global Index Medicus from inception until January 2022. The meta-analysis was performed using a random-effects model. Sources of heterogeneity were investigated using subgroup analysis, while funnel plots and Egger tests were performed to assess publication bias. This review was registered in PROSPERO with the number CRD42022299498. A total of 8254 articles were found in the searched databases. After the exclusion of duplicated articles and others for multiple reasons, we finally obtained 26 articles that met all inclusion criteria. Worldwide, we recorded separately 22 maternal outcomes and 22 foetal outcomes among pregnant women with BV. When analyzing the different worldwide outcomes combined, there are 5 maternal-fetal outcomes that have been reported with the highest prevalence namely preterm birth, < 37 wGA (17.9% [95%CI= 13-23.3]), mechanical ventilation (15.2% [95%CI= 0-45.9]), low birth weight, < 2500 g (14.2% [95%CI= 9.1-20.1]), premature rupture of membrane, < 37 wGA (13.2% [95%CI= 6.1-22.3]) and neonatal intensive care unit admission (11.2 % [95%CI= 0-53.5]). We also found that at the level of the WHO Region, South-East Asia records the highest prevalence of maternal-foetal outcomes (25.5 % [95%CI = 17.5-34.4]) followed by Africa with a prevalence of (24.6% [95%CI= 16.8-33.4]). At the diagnostic level, we obtained the greatest prevalence (37.2% [95%CI= 23-52.6]) for BV diagnosed with Amsel criteria, then blue test (31.7 % [95%CI= 8.4-60.6]). When considering gestation age, we obtained a high prevalence (29.6% [95%CI= 21.2-38.8]) among pregnant women with BV diagnosed in the third trimester of pregnancy. Even if BV is one of the most common vaginal conditions, the repartition of the type of maternal-foetal outcomes among pregnant women positive for BV is grandly disproportional among countries and continents
Kenfack Zanguim Marie Josiane, Sebastien Kenmoe, Jean Thierry Ebogo-Belobo, Arnol Bowo-Ngandji, Donatien Serge Mbaga, Airy Barriere Yetgang Fodjo, Cyprien Kengne-Ndec, Livo Esemu, Jude Bigoga, Rosette Megnekou
Presenting author affiliation: University of Yaounde 1, Cameroon
Functional screens of barcoded expression libraries uncover new gene functions in carbon utilization among gut Bacteroidales
A mechanistic understanding of host-microbe interactions in the gut microbiome is hindered by poorly annotated bacterial genomes. While functional genomics can generate large gene-to-phenotype datasets to accelerate gene discovery, their applications to study gut anaerobes have been limited. For instance, most gain-of-function screens of gut bacterial genes have been performed in an aerobic host and included a small number of conditions. To address these challenges, we developed a strategy to barcode expression libraries for high-throughput interrogation of gene functions in competitive fitness assays. We demonstrate the power of this approach to uncover novel phenotypes for uncharacterized genes using pooled libraries constructed from a diverse set of gut Bacteroidales expressed in Bacteroides thetaiotaomicron. We identified new roles in carbohydrate metabolism for nine proteins, including enzymes, transporters, a regulator, and hypothetical proteins from mobile genetic elements. This approach can be readily applied to other organisms and additional phenotypic assays.
Link to OA paper: https://www.biorxiv.org/content/10.1101/2022.10.10.511384v2
Yolanda Y. Huang, Morgan Price, Allison Hung, Omree Gal-Oz, Davian Ho, Heloise Carion, Adam Deutschbauer, Adam Arkin
Presenting author affiliation: Lawrence Berkeley National Laboratory, California, US
BugSigDB: A Comprehensive Database of Published Microbial Signatures for Epidemiological Analysis of Microbiome Data
Most microbiome studies report “signatures” of differentially abundant microbial taxa for a disease or exposure of interest, but heterogeneity in how complex methods and results are reported make comparisons between studies difficult. A signature represents statistically different bacterial taxa identified in a given study and represents a summary of a study’s findings. These signatures can be assessed across studies for consistency and agreement. BugSigDB is a manually curated database of microbial signatures collected from published microbiome differential abundance studies. Key information for each study is curated including study design, sample size, participant information, laboratory methods, and statistical methods in a structured, standardized format. BugSigDB is open source and available for researchers to use and contribute to. As of January 11th, 2022 it contains 2,107 microbial signatures curated from 522 published microbiome research articles. We present an applied example of use of BugSigDB gut microbiome signatures for COVID-19. Analysis of 132 signatures from 32 studies of COVID-19 and the gut microbiome reveal significant co-occurrence of several bacterial taxa within the phylum Firmicutes along with Actinobacteria, Bacteriodetes, and Proteobacteria (Figure 1). Across these studies, the genera Bacteroides and Alistipes were statistically found to be in decreased abundance among COVID-19 patients. bugsigdbr, an accompanying open source R/Bioconductor package, provides signatures and accompanying data downloads in a tidy data format. Data can also be accessed via a semantic wiki web interface at https://bugsigdb.org. Together, they allow for efficient systematic analysis of findings from microbiome studies across a variety of diseases and conditions of interest.
Chloe Anya Mirzayi, Ludwig Geistlinger, Heidi E Jones, Levi Waldron
Presenting author affiliation: CUNY Graduate School of Public Health and Health Policy, Institute for Implementation Science in Public Health, New York, NY, USA
A Resource of Microbiome Benchmark Datasets with Biological Ground Truth
Little consensus exists about which statistical methods are most suitable for identifying differentially abundant (DA) taxa in microbiome research. A limitation of benchmarking DA methods is the lack of datasets with ground truth. Here, we introduce the MicrobiomeBenchmarkData package/resource of datasets with known biological ground truth and varying ecological complexity. We compiled and standardized three datasets: 1) a high-diversity dataset from the Human Microbiome Project contrasting subgingival and supragingival oral plaques using both 16S and shotgun data, 2) a low-diversity 16S dataset of healthy vaginal and bacterial vaginosis samples, and 3) a 16S spike-in dataset containing fixed amounts of foreign spiked-in bacteria across stool samples of patients who underwent allogeneic stem transplantation. We used the first two datasets to benchmark 17 differential abundance methods broadly categorized as classical, compositional, microbiome-specific, RNA-seq, and scRNA-seq tests. We used the third dataset to assess low variability of spiked-in bacteria. Overall, RNAseq methods performed best in the high-diversity dataset (gingiva) while most methods performed well in the low-diversity dataset (vagina). Notably, compositional methods proposed specifically for microbiome data analysis, performed equivalently to other methods in the high-complexity dataset but produced spurious results in the low-diversity dataset and increased unwanted variability of spike-in bacteria. The MicrobiomeBenchmarkData project aims to be a gold-standard resource of microbiome datasets for benchmarking DA methods based on biologically relevant signatures, following the data FAIRness principles of Findability, Accessibility, Interoperability, and Reusability. Datasets are available as TSV text files through Zenodo (https://doi.org/10.5281/zenodo.6911026), and as TreeSummarizedExperiment class objects through the MicrobiomeBenchmarkData R/Bioconductor package (https://waldronlab.io/MicrobiomeBenchmarkData).
Samuel David Gamboa-Tuz, Marcel Ramos, Levi Waldron
Presenting author affiliation: CUNY Graduate School of Public Health and Health Policy, New York, USA
OPEN-ACCESS PAPER HIGHLIGHTS:
A novel taurine-respiring murine gut bacterium contributes to colonization resistance against enteropathogens
Taurine-respiring gut bacteria produce H2S with ambivalent impact on host health. We report the isolation and genomic-ecophysiological characterization of the first taurine-respiring mouse gut bacterium. Taurinivorans muris represents a new widespread species with protective capacity against pathogens and differs from the human gut sulfidogen Bilophila wadsworthia in its sulfur metabolism and host distribution. Despite alternative physiologies, taurine respiration was the main in vivo lifestyle of T. muris independent of mouse diet and genotype. In gnotobiotic mice, T. muris selectively enhanced the activity of a sulfur metabolism gene-encoding prophage and provided slightly increased colonization resistance against Salmonella Typhimurium, which showed reduced expression of galactonate catabolism genes. We identified T. muris as the dominant sulfidogen of a mouse microbiota that conferred H2S-mediated protection against Klebsiella pneumoniae in a previous study. Together, we revealed the realized physiological niche of a key murine gut sulfidogen and its impact on pathogen and phage gene expression.
Link to OA paper: https://www.biorxiv.org/content/10.1101/2022.10.05.510937v1
Huimin Ye, Sabrina Borusak, Claudia Eberl, Buck T. Hanson, Benjamin Zwirzitz, Craig W. Herbold, Petra Pjevac, Bela Hausmann, Bärbel Stecher, David Schleheck, Alexander Loy
Presenting author affiliation: Division of Microbial Ecology, Centre for Microbiology and Environmental Systems Science, University of Vienna, Vienna, Austria