The increasing evidence pointing towards the involvement of the gut microbiome in multiple diseases, as well as its plasticity, renders it a desirable potential therapeutic target. Nevertheless, classical therapies based on the consumption of live probiotic bacteria, or their enrichment by prebiotics, exhibit limited efficacy. Recently, a novel therapeutic approach has been suggested based on metabolites secreted, modulated or degraded by the microbiome. As many of the host–microorganism interactions pertaining to human health are mediated by metabolites, this approach may be able to provide therapeutic efficacy while overcoming caveats of current microbiome-targeting therapies, such as colonization resistance and inter-individual variation in microbial composition. In this Perspective, we will discuss the evidence that supports pursuing the metabolite-based therapeutic approach as well as issues critical for its implementation. In a broader context, we will discuss how recent advances in microbiome research may improve and refine current treatment modalities, and the potential of combining them with metabolite-based interventions as a means of achieving a person-specific, integrated and efficient therapy.
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We thank the members of the Elinav Lab for fruitful discussions. We apologize to authors whose relevant work was not included in this Perspective owing to space constraints. J.S. is the recipient of the Strauss Institute research fellowship. E.E. is supported by Y. Ungar and R. Ungar, Israel; the Abisch Frenkel Foundation for the Promotion of Life Sciences; the Gurwin Family Fund for Scientific Research; the Leona M. and Harry B. Helmsley Charitable Trust; the Crown Endowment Fund for Immunological Research; the estate of J. Gitlitz; the estate of L. Hershkovich; the Benoziyo Endowment Fund for the Advancement of Science; the Adelis Foundation; J.L. Schwartz and V. Schwartz, Pacific Palisades; A. Markovitz, Canada; C. Adelson, Canada; CNRS (Centre National de la Recherche Scientifique); the estate of S. Weber and A.J. Weber; Mr and Mrs D.L. Schwarz, Sherman Oaks; grants funded by the European Research Council; the Kenneth Rainin Foundation; the German-Israel Binational Foundation; the Israel Science Foundation; the Minerva Foundation; the Rising Tide Foundation; and the Alon Foundation Scholar Award. E.E. is the incumbent of the Rina Gudinski Career Development Chair and is a senior fellow, CIFAR (Canadian Institute for Advanced Research).
The authors declare no competing financial interests.
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Suez, J., Elinav, E. The path towards microbiome-based metabolite treatment. Nat Microbiol 2, 17075 (2017). https://doi.org/10.1038/nmicrobiol.2017.75
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