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Future events·

Monday, November 20, 2023

MVIF.28 | 16/17 & 18 April 2024

with Keynote talk by Prof. Julia Oh

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Molecular mechanisms of microbial modulation of skin homeostasis

by Prof. Julia Oh

Abstract:

The human skin harbors an abundant microbial ecosystem with bidirectional metabolic exchanges supporting symbiotic and commensal functions. Metagenomic analyses of the diverse skin sites in healthy humans demonstrate that contrasting forces of the skin’s biogeography and individual characteristics shape the skin microbiome and the dynamics of its bacteria, fungi, and viruses. However, we have shown that shifts in the ecological properties of the skin microbiome are significantly associated with aging, skin disease, disease severity, and monogenic skin and immune disorders. We have used a variety of computational and functional approaches, including metagenomics, CRISPRi screening, organoid platforms, transcriptomic and spatial transcriptomics, and other technologies to probe genetic and functional diversity of the skin microbiome.

Short Bio:

Julia Oh received her B.A. from Harvard University, her Ph.D. in genetics from Stanford University, and postdoctoral training at the National Institutes of Health. Now an associate professor at the Jackson Laboratory, Dr. Oh is a microbiome expert with a focus on combining high-resolution computational reconstructions of the microbiome with microbial engineering to devise innovative approaches to create new therapeutic interventions and investigate the underlying ecology of skin microbial communities.


Short talks

Data-driven prediction of colonization outcomes for complex microbial communities

Microbial interactions can lead to different colonization outcomes of exogenous species, be they pathogenic or beneficial in nature. Predicting the colonization of exogenous species in complex communities remains a fundamental challenge in microbial ecology, mainly due to our limited knowledge of the diverse mechanisms governing microbial dynamics. Here, we propose a data-driven approach independent of any dynamics model to predict colonization outcomes of exogenous species from the baseline compositions of microbial communities. We systematically validate this approach using synthetic data, finding that machine learning models can predict not only the binary colonization outcome but also the post-invasion steady-state abundance of the invading species. Then we conduct colonization experiments for commensal gut bacteria species Enterococcus faecium and Akkermansia muciniphila in hundreds of human stool-derived in vitro microbial communities, confirming that the data-driven approaches can predict the colonization outcomes in experiments. Furthermore, we find that while most resident species are predicted to have a weak negative impact on the colonization of exogenous species, strongly interacting species could significantly alter the colonization outcomes, e.g., Enterococcus faecalis inhibits the invasion of E. faecium invasion. The presented results suggest that the data-driven approaches are powerful tools to inform the ecology and management of microbial communities.

Lu Wu, CAS Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China

Link to OA paper: https://doi.org/10.1038/s41467-024-46766-y

A catalogue of small proteins from the global microbiome

Small Open Reading Frames (smORFs, operationally defined as those with fewer than 100 codons) are often neglected due to the limitation of computational and experimental methods. Recently, systematic studies have shown that smORFs are widely distributed ecologically and perform diverse functions. However, little is known about the distribution and role of smORFs in the global microbiome. Therefore, we constructed the global microbial smORFs catalogue (GMSC) from 63,410 publicly-available metagenomes across 72 distinct habitats and 87,920 high-quality isolated microbial genomes. GMSC (available at https://gmsc.big-data-biology.org/) contains 964,970,496 non-redundant smORFs, the majority of which are novel. We found that archaea harbor more small proteins than bacteria (as a fraction of their genomes). To enable the use of this resource, we provide a tool called GMSC-mapper that can identify and annotate reliable smORFs from microbial genomes and metagenomes. The resource shows an immense and underexplored diversity of smORFs and can be used to research the presence, distribution, and role of smORFs at the global scale.

Yiqian Duan, Fudan University, China

Link to preprint: https://www.biorxiv.org/content/10.1101/2023.12.27.573469v1

Comprehensive analyses of a large human gut Bacteroidales culture collection reveal species and strain level diversity and evolution

Species of the Bacteroidales order are among the most abundant and stable bacterial members of the human gut microbiome with diverse impacts on human health. While Bacteroidales strains and species are genomically and functionally diverse, order-wide comparative analyses are lacking. We cultured and sequenced the genomes of 408 Bacteroidales isolates from healthy human donors representing nine genera and 35 species and performed comparative genomic, gene-specific, mobile gene, and metabolomic analyses. Families, genera, and species could be grouped based on many distinctive features. However, we also show extensive DNA transfer between diverse families, allowing for shared traits and strain evolution. Inter- and intra-specific diversity is also apparent in the metabolomic profiling studies. This highly characterized and diverse Bacteroidales culture collection with strain-resolved genomic and metabolomic analyses can serve as a resource to facilitate informed selection of strains for microbiome reconstitution.

Zhenrun Jerry Zhang, University of Chicago, USA

Link to preprint: https://www.biorxiv.org/content/10.1101/2024.03.08.584156v1


Highlights

Maternal smoking during pregnancy increases the risk of gut microbiome-associated childhood overweight and obesity

Childhood obesity is linked to maternal smoking during pregnancy. Gut microbiota may partially mediate this association and could be potential targets for intervention; however, its role is understudied. We included 1,592 infants from the Canadian Healthy Infants Longitudinal Development Cohort. Data on environmental exposure and lifestyle factors were collected prenatally and throughout the first three years. Weight outcomes were measured at one and three years of age. Stool samples collected at 3 and 12 months were analyzed by sequencing the V4 region of 16S rRNA to profile microbial compositions and magnetic resonance spectroscopy to quantify the metabolites. We showed that quitting smoking during pregnancy did not lower the risk of offspring being overweight. However, exclusive breastfeeding until the third month of age may alleviate these risks. We also reported that maternal smoking during pregnancy significantly increased Firmicutes abundance and diversity. We further revealed that Firmicutes diversity mediates the elevated risk of childhood overweight and obesity linked to maternal prenatal smoking. This effect possibly occurs through excessive microbial butyrate production. These findings add to the evidence that women should quit smoking before their pregnancies to prevent microbiome-mediated childhood overweight and obesity risk, and indicate the potential obesogenic role of excessive butyrate production in early life.

Ye Peng, The Jockey Club School of Public Health and Primary Care, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, SAR, China

Link to OA paper: https://www.tandfonline.com/doi/full/10.1080/19490976.2024.2323234

Cas9-Assisted Biological Containment of a Genetically Engineered Human Commensal Bacterium and Genetic Elements

Sophisticated gene circuits built by synthetic biology can enable bacteria to sense their environment and respond predictably. Engineered biosensing bacteria outfitted with such circuits can potentially probe the human gut microbiome to prevent, diagnose, or treat disease. To provide robust biocontainment for engineered bacteria, we devised a Cas9-assisted auxotrophic biocontainment system combining thymidine auxotrophy, an Engineered Riboregulator (ER) for controlled gene expression, and a CRISPR Device (CD). The CD prevents the engineered bacteria from acquiring thyA via horizontal gene transfer, which would disrupt the biocontainment system, and inhibits the spread of genetic elements by killing bacteria harboring the gene cassette. This system tunably controlled gene expression in the human gut commensal bacterium Bacteroides thetaiotaomicron, prevented escape from thymidine auxotrophy, and blocked transgene dissemination. These capabilities were validated in vitro and in vivo. This biocontainment system exemplifies a powerful strategy for bringing genetically engineered microorganisms safely into biomedicine.

Naoki Hayashi, Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, USA; JSR-Keio University Medical and Chemical Innovation Center (JKiC), JSR Corp., Tokyo, Japan.

Link to OA paper: https://www.nature.com/articles/s41467-024-45893-w