4.8 Review

Emerging targetome and signalome landscape of gut microbial metabolites

Journal

CELL METABOLISM
Volume 34, Issue 1, Pages 35-58

Publisher

CELL PRESS
DOI: 10.1016/j.cmet.2021.12.011

Keywords

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Funding

  1. National Natural Science Foundation of China [81720108032, 81930109, 81973556]
  2. National Key Research and Development Programme of China [2021YFA1301300]
  3. Project for Major New Drug Innovation and Development [2018ZX09711001-002-003]
  4. Project of State Key Laboratory of Natural Medicines, China Pharmaceutical University [SKLNMZZ202020]

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The interaction between microbial metabolites and host targets plays a crucial role in signal transmission and biological regulation. Understanding the interaction between microbial metabolites and host targets can provide new insights into host health and disease, expand the range of druggable targets, and inspire drug design and discovery.
The gut microbiome produces chemically diverse small molecules to interact with the host, conveying signals from the gut to the whole system. The microbial metabolites feature several unique modes of interaction with host targets, which fits well into the balanced and networked fashion of biological regulation. Hence, fully unveiling the targetome of signaling microbial metabolites may offer new insights into host health and disease, expand the repertoire of druggable targets, and enlighten a bioinspired path to drug design and discovery. In this review, we present an updated understanding of how microbial metabolite interaction with host targets finely orchestrates and integrates multiple signals to pathophysiological phenotypes, contributing new insights into organ crosstalk and holistic homeostasis maintenance in biological systems. We discuss strategies and open questions for mining and biomimicking the microbial metabolite-targetome interactions for pharmacological manipulation, which may lead to a new paradigm of drug discovery.

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