Microbiota-targeted therapies: an ecological perspective.
The connection between disease and the disruption of homeostatic interactions between the host and its microbiota is now well established. Drug developers and clinicians are starting to rely more heavily on therapies that directly target the microbiota and on the ecology of the microbiota to understand the outcomes of these treatments. The effects of those microbiota-targeted therapies that alter community composition range in scale from eliminating individual strains of a single species (for example, with antibacterial conjugate vaccines) to replacing the entire community with a new intact microbiota (for example, by fecal transplantation). Secondary infections linked to antibiotic use provide a cautionary tale of the unintended consequences of perturbing a microbial species network and highlight the need for new narrow-spectrum antibiotics with rapid companion diagnostics. Insights into microbial ecology will also benefit the development of probiotics, whose therapeutic prospects will depend on rigorous clinical testing. Future probiotics may take the form of a consortium of long-term community residents: "a fecal transplant in a capsule." The efficacy of microbiota-targeted therapies will need to be assessed using new diagnostic tools that measure community function rather than composition, including the temporal response of a microbial community to a defined perturbation such as an antibiotic or probiotic.
Department of Molecular Genetics, The Forsyth Institute, Cambridge, MA 02142, USA. klemon@forsyth.org
Katherine P
KP
Lemon
Gary C
GC
Armitage
David A
DA
Relman
Michael A
MA
Fischbach
D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D006801:Humans; D054892:Metagenome / Q000187:drug effects / Q000502:physiology*; D019936:Probiotics / Q000627:therapeutic use
D000900:Anti-Bacterial Agents