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Investigating host-microbiome interactions by droplet based microfluidics

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Tauzin, Alexandra S. 
Pereira, Mariana Rangel 
Van Vliet, Liisa D. 
Colin, Pierre-Yves 
Laville, Elisabeth 


Abstract: Background: Despite the importance of the mucosal interface between microbiota and the host in gut homeostasis, little is known about the mechanisms of bacterial gut colonization, involving foraging for glycans produced by epithelial cells. The slow pace of progress toward understanding the underlying molecular mechanisms is largely due to the lack of efficient discovery tools, especially those targeting the uncultured fraction of the microbiota. Results: Here, we introduce an ultra-high-throughput metagenomic approach based on droplet microfluidics, to screen fosmid libraries. Thousands of bacterial genomes can be covered in 1 h of work, with less than ten micrograms of substrate. Applied to the screening of the mucosal microbiota for β-N-acetylgalactosaminidase activity, this approach allowed the identification of pathways involved in the degradation of human gangliosides and milk oligosaccharides, the structural homologs of intestinal mucin glycans. These pathways, whose prevalence is associated with inflammatory bowel diseases, could be the result of horizontal gene transfers with Bacteroides species. Such pathways represent novel targets to study the microbiota-host interactions in the context of inflammatory bowel diseases, in which the integrity of the mucosal barrier is impaired. Conclusion: By compartmentalizing experiments inside microfluidic droplets, this method speeds up and miniaturizes by several orders of magnitude the screening process compared to conventional approaches, to capture entire metabolic pathways from metagenomic libraries. The method is compatible with all types of (meta)genomic libraries, and employs a commercially available flow cytometer instead of a custom-made sorting system to detect intracellular or extracellular enzyme activities. This versatile and generic workflow will accelerate experimental exploration campaigns in functional metagenomics and holobiomics studies, to further decipher host-microbiota relationships. BEyZgKg3YsWtKJ_ei8gXkiVideo Abstract


Funder: Royal Society Newton fellowship

Funder: CAPES Scholarship - Brazil


Research, Functional metagenomics, Droplet microfluidics, Human gut microbiota, Human glycans, Beta-N-acetyl-galactosaminidase

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BioMed Central
H2020 Marie Skłodowska-Curie Actions (MSCA-IF-2015-707457)
H2020 LEIT Biotechnology (LEIT‐BIO‐2015‐685474, LEIT‐BIO‐2015‐685474)
European Research Council (695669)