Molecular tools for probing the microbiome

Abstract

The microbiome plays essential roles in health and disease. Our understanding of the imbalances that can arise in the microbiome and their consequences is held back by a lack of technologies that selectively knock out members of these microbial communities. Antibiotics and fecal transplants, the existing methods for manipulating the microbiota of the gastrointestinal tract, are not sufficiently pinpointed to reveal how particular microbial genes, strains, or species affect human health. A toolset for the precise manipulation of the microbiome could significantly advance disease diagnosis and treatment. Here, we provide an overview of current and future strategies for the development of molecular tools that can be used to probe the microbiome without producing off-target effects.

Figure 1. Schematic of the current tools available for probing the microbiome.

Computational techniques coupled with efficient high-throughput experimental platforms are being used for the targeted engineering of microbiome communities. Advances in synthetic biology have enabled CRISPR and engineered bacteriophages to be used as targeted molecular tools capable of reconfiguring bacterial communities. Recent reports have also revealed that small molecules, such as proteins and peptides, possess selective activity towards certain bacterial genera and species, opening up numerous opportunities for ways to sculpt the microbiome.

Figure 2. Molecular tools for sculpting the microbiome.

(a) Identification of bacterial targets by CRISPR enable probing the gut microbiome [27,28]. (b) Bacteriophages have been engineered ex vivo for the manipulation of bacterial communities in the gut [34,35]. (c) Stable peptides have been used to selectively target oral bacteria by interacting with specific bacterial components [42,43].