Targeting the human gut microbiome with small-molecule inhibitors
Abstract
The human gut microbiome is a complex microbial community that is strongly linked to both host health and disease. However, the detailed molecular mechanisms underlying the effects of these microorganisms on host biology remain largely uncharacterized. The development of non-lethal, small-molecule inhibitors that target specific gut microbial activities enables a powerful but underutilized approach to studying the gut microbiome and a promising therapeutic strategy. In this Review, we will discuss the challenges of studying this microbial community, the historic use of small-molecule inhibitors in microbial ecology, and recent applications of this strategy. We also discuss the evidence suggesting that host-targeted drugs can affect the growth and metabolism of gut microbes. Finally, we address the issues of developing and implementing microbiome-targeted small-molecule inhibitors and define important future directions for this research.
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It is difficult to predict and control the outcomes of microbiome manipulation by prebiotics because they affect the growth and activities of multiple microbial species.
“On the other hand, it is difficult to predict and control the outcomes of microbiome manipulation by prebiotics, as they affect the growth and activities of multiple microbial species.728,741”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [741]
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Alpha-Glucosidase Inhibitors Alter Gut Microbiota and Ameliorate Collagen-Induced Arthritis
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Pharmacomicrobiomics: The Role of the Gut Microbiome in Immunomodulation and Cancer Therapy
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Circulating Gut Microbe-Derived Metabolites Are Associated with Hepatocellular Carcinoma
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A Small-Molecule Inhibitor of Gut Bacterial Urease Protects the Host from Liver Injury
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- Authors
- Woo, A. Y. M., Aguilar Ramos, M. A., Narayan, R., Richards-Corke, K. C., Wang, M. L., Sandoval-Espinola, W. J., & Balskus, E. P.
- Affiliations
- Harvard University (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Balskus, Emily P.
- ORCID
- Venue
- Nature Reviews Chemistry
- Published
- 2023-04-18
- Volume
- 7
- Issue
- 5
- Pages
- 319-339
- ISSN
- 2397-3358 (ISSN-L)
- OpenAlex
- W4366277385
- Cited by
- 42
- References
- 244
- Citations by year
- 2026: 11 · 2025: 12 · 2024: 17 · 2023: 2
- FWCI
- 1.11
- Type
- journal article
- Language
- en
- Update notices
- correction (2023-06-13)
- Open access
- closed
- Licence
- Locations
- Nature Reviews Chemistry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Agricultural and Biological Sciences › Food Science › Probiotics and Fermented Foods
- Health Sciences › Medicine › Pharmacology › Microbial Natural Products and Biosynthesis
- Keywords
- gut microbiota, small molecule inhibitors, microbiota-based therapy, microbial metabolism, microbial ecology, drug design
- MeSH terms
- Gastrointestinal Microbiome, Humans, Microbiota
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