Targeted Approaches for In Situ Gut Microbiome Manipulation

Abstract

Microbial communities and their collective genomes form the gut microbiome, of which bacteria are the major contributor. Through their secreted metabolites, bacteria interact with the host, influencing human health and physiology. Perturbation of the microbiota and metabolome has been associated with various diseases and metabolic conditions. As knowledge on fundamental host-microbiome interactions and genetic engineering tools becomes readily available, targeted manipulation of the gut microbiome for therapeutic applications gains favourable attention. Manipulation of the gut microbiome can be achieved by altering the microbiota population and composition, or by modifying the functional metabolic activity of the microbiome to promote health and restore the microbiome balance. In this article, we review current works that demonstrate various strategies employed to manipulate the gut microbiome in situ to various degrees of precision.

Keywords: CRISPR-Cas9; gut microbiome; microbiome modulation; phage; prebiotics; probiotics.

Figure 1

Overview of targeted methods to manipulate the gut microbiome. (a) Administration of targeted prebiotics to stimulate the growth of beneficial microbes; (b) use of targeted probiotics and engineered probiotics to eliminate pathogens or directly change the functional output of the gut microbiome; and (c) use of bacteriophages to eliminate specific species of pathogens or target pathogens with certain genes.

Figure 2

Cross-feeding effect between Bifidobacterium and butyrate-producing bacteria. Bifidobacterium utilises supplemented prebiotics, which stimulates their growth. Acetate produced by Bifidobacterium becomes a carbon source for butyrate-producing microbes, stimulating their growth and butyrate-producing activities and, in turn, modulating the microbiome function and improving gut health.