Abstract
Our bodies are colonized by a complex ecosystem of bacteria, unicellular eukaryotes and their viruses that together play a major role in our health. Over the past few years tools derived from the prokaryotic immune system known as CRISPR-Cas have empowered researchers to modify and study organisms with unprecedented ease and efficiency. Here we discuss how various types of CRISPR-Cas systems can be used to modify the genome of gut microorganisms and bacteriophages. CRISPR-Cas systems can also be delivered to bacterial population and programmed to specifically eliminate members of the microbiome. Finally, engineered CRISPR-Cas systems can be used to control gene expression and modulate the production of metabolites and proteins. Together these tools provide exciting opportunities to investigate the complex interplay between members of the microbiome and our bodies, and present new avenues for the development of drugs that target the microbiome.This article is part of a discussion meeting issue ‘The ecology and evolution of prokaryotic CRISPR-Cas adaptive immune systems’.
Highlights
Healthy humans live in a symbiotic relationship with trillions of microorganisms that inhabit the exposed surfaces of our bodies and play an essential role in the maturation of the host-immune response, production of metabolites, brain–gut axis and more
We describe how tools derived from the prokaryotic immune system known as clustered regularly interspaced short palindromic repeats (CRISPRs)—and CRISPR-associated (Cas) proteins can be used to modify or eliminate members of the microbiome
The Cas nucleases are guided by CRISPR RNAs, produced by transcription and processing of the CRISPR locus: a chromosomal site into which DNA fragments from invading nucleic acids are integrated in between repeats, providing a memory of past infections
Summary
Healthy humans live in a symbiotic relationship with trillions of microorganisms that inhabit the exposed surfaces of our bodies and play an essential role in the maturation of the host-immune response, production of metabolites, brain–gut axis and more (see reviews [1,2,3,4]) This close relationship makes our microbiome an interesting target for therapies with the goal to induce desired responses, immunological, metabolic or even neurological in nature. These therapies can be classified into three main types: (i) additive therapies supplementing the host microbiota with individual strains or consortiums of bacterial species, (ii) subtractive therapies aiming to eliminate disease-causing members of the microbiome, and (iii) modulatory therapies aiming to modulate the composition or activity of the endogenous microbiome (see reviews [5,6]). CRISPR-Cas systems offer a powerful set of tools that will benefit the study of the microbiome and lead to the development of new strategies to modify it (figure 2)
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