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What can microfluidics do for human microbiome research?

ABSTRACT: Dysregulation of the human microbiome has been linked to various disease states, which has galvanized the efforts to modulate human health through microbiomes. Currently, human microbiome research is going through several phases to identify the constituent components of the microbiome, associate microbiome changes with physiological and pathological states, understand causative relationships, and finally translate this knowledge into therapeutics and diagnostics. The convergence of microfluidic technologies with molecular and cell profiling, microbiology, and tissue engineering can potentially be applied to these different phases of microbiome research to overcome the existing challenges faced by conventional approaches. The goal of this paper is to discuss and highlight the opportunities of applying different microfluidic technologies to specific areas of microbiome research as well as unique challenges that microfluidics must overcome when working with microbiome-relevant biological materials, e.g., micro-organisms, host tissues, and fluids. We will discuss the applicability of integrated microfluidic systems for processing biological samples for genomic sequencing analyses. For functional analysis of the microbiota, we will cover state-of-the-art microfluidic devices for microbiota cultivation and functional measurements. Finally, we highlight the use of organs-on-chips to model various microbiome–host tissue interactions. We envision that microfluidic technologies may hold great promise in advancing the knowledge on the interplay between microbiome and human health, as well as its eventual translation into microbiome-based diagnostics and therapeutics.

SUBMITTER: Tan H

PROVIDER: S-EPMC7538166 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Project description:BackgroundDespite 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.ResultsHere, 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.ConclusionBy 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. Video Abstract.

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What can microfluidics do for human microbiome research?

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