Targeting the human gut microbiome with small-molecule inhibitors

Highly accurate protein structure prediction with AlphaFold

Jumper, J., Evans, R., Pritzel, A., Green, T., Figurnov, M., Ronneberger, O., Tunyasuvunakool, K., Bates, R., Žídek, A., Potapenko, A., et al. (2021) · Nature · doi:10.1038/s41586-021-03819-2 · Cited by 43,764

Structure, function and diversity of the healthy human microbiome

The Human Microbiome Project Consortium (2012) · Nature · doi:10.1038/nature11234 · Cited by 11,726

Dietary Modulation of the Human Colonic Microbiota: Introducing the Concept of Prebiotics

Gibson, G. R., & Roberfroid, M. B. (1995) · Journal of Nutrition · doi:10.1093/jn/125.6.1401 · Cited by 7,659

Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease

Wang, Z., Klipfell, E., Bennett, B. J., Koeth, R., Levison, B. S., DuGar, B., Feldstein, A. E., Britt, E. B., Fu, X., Chung, Y.-M., et al. (2011) · Nature · doi:10.1038/nature09922 · Cited by 5,597

Probiotics in man and animals

AFRC, R. F. (1989) · Journal of Applied Bacteriology · doi:10.1111/j.1365-2672.1989.tb05105.x · Cited by 4,831

Interaction between microbiota and immunity in health and disease

Zheng, D., Liwinski, T., & Elinav, E. (2020) · Cell Research · doi:10.1038/s41422-020-0332-7 · Cited by 3,947

Current understanding of the human microbiome

Gilbert, J. A., Blaser, M. J., Caporaso, J. G., Jansson, J. K., Lynch, S. V., & Knight, R. (2018) · Nature Medicine · doi:10.1038/nm.4517 · Cited by 2,609

Population-level analysis of gut microbiome variation

Falony, G., Joossens, M., Vieira-Silva, S., Wang, J., Darzi, Y., Faust, K., Kurilshikov, A., Bonder, M. J., Valles-Colomer, M., Vandeputte, D., et al. (2016) · Science · doi:10.1126/science.aad3503 · Cited by 2,400

Topoisomerase I inhibitors: camptothecins and beyond

Pommier, Y. G. (2006) · Nature reviews. Cancer · doi:10.1038/nrc1977 · Cited by 2,362

Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases

Loh, J. S., Mak, W. Q., Tan, L. K. S., Ng, C. X., Chan, H. H., Yeow, S. H., Foo, J. B., Ong, Y. S., How, C. W., & Khaw, K. Y. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01743-1 · Cited by 1,193

Another renaissance for bile acid gastrointestinal microbiology

Ridlon, J. M., & Gaskins, H. R. (2024) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-024-00896-2 · Cited by 205

Hydrogen sulfide produced by the gut microbiota impairs host metabolism via reducing GLP-1 levels in male mice

Qi, Q., Zhang, H., Jin, Z., Wang, C., Xia, M., Chen, B., Lv, B., Diaz, L. P., Li, X., Feng, R., et al. (2024) · Nature Metabolism · doi:10.1038/s42255-024-01068-x · Cited by 129

Horizon scanning the application of probiotics for wildlife

Garcías-Bonet, N., Roik, A., Tierney, B. T., García, F. C., Villela, H., Dungan, A. M., Quigley, K. M., Sweet, M. J., Berg, G., Gram, L., et al. (2023) · Trends in Microbiology · doi:10.1016/j.tim.2023.08.012 · Cited by 81

Pharmacomicrobiomics: The Role of the Gut Microbiome in Immunomodulation and Cancer Therapy

Bolte, L. A., Björk, J. R., Gaćeša, R., & Weersma, R. K. (2025) · Gastroenterology · doi:10.1053/j.gastro.2025.04.025 · Cited by 39

Recent developments in the enzymatic modifications of steroid scaffolds

Wang, H., & Abe, I. (2024) · Organic & Biomolecular Chemistry · doi:10.1039/d4ob00327f · Cited by 36

Circulating Gut Microbe-Derived Metabolites Are Associated with Hepatocellular Carcinoma

Banerjee, R., Wehrle, C. J., Wang, Z., Wilcox, J. D., Uppin, V., Varadharajan, V., Mrdjen, M., Hershberger, C. E., Reizes, O., Yu, J. S., et al. (2024) · Biomedicines · doi:10.3390/biomedicines12091946 · Cited by 25

The impact of the human gut microbiome on the treatment of autoimmune disease

Nayak, R. R., & Orellana, D. A. (2024) · Immunological Reviews · doi:10.1111/imr.13358 · Cited by 23

Emerging chemophysiological diversity of gut microbiota metabolites

Lin, X., He, K., Gu, Z., & Zhao, X. (2024) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2024.07.006 · Cited by 23

Review on the Function, Substrate Affinity, and Potential Application of Bile Salt Hydrolase Originated from Probiotic Strains of Lactobacillus, Bifidobacterium, and Enterococcus

Kang, M. H., Elnar, A. G., & Kim, G.-B. (2025) · Food Science of Animal Resources · doi:10.5851/kosfa.2025.e1 · Cited by 21

Therapeutic role of gut microbiota in lung injury-related cognitive impairment

Cheng, Y., Hu, G., Deng, L., Zan, Y., & Chen, X. (2025) · Frontiers in Nutrition · doi:10.3389/fnut.2024.1521214 · Cited by 19

Insights into the gut-liver axis: mechanisms and emerging therapies in hepatocellular carcinoma

Hu, Y., Gao, M., Chenghuang, J., & Bao, R. (2025) · Frontiers in Pharmacology · doi:10.3389/fphar.2025.1595853 · Cited by 16

Bacteroides intestinalis mediates the sensitivity to irinotecan toxicity via tryptophan catabolites

Hou, Y., Wu, H., Zhang, Z., Wang, J., Chen, Q., Lian, C., He, D., Li, Z., Wei, W., Lin, X., et al. (2025) · Gut · doi:10.1136/gutjnl-2024-334699 · Cited by 14

Chemical genetic approaches to dissect microbiota mechanisms in health and disease

Yang, X., & Hang, H. C. (2024) · Science · doi:10.1126/science.ado8548 · Cited by 16

Tissue-resident bacteria in metabolic diseases: emerging evidence and challenges

Massier, L., Musat, N., Stümvoll, M., Tremaroli, V., Chakaroun, R., & Kovacs, P. L. (2024) · Nature Metabolism · doi:10.1038/s42255-024-01065-0 · Cited by 15

B12‐Dependent Radical SAM Enzymes Catalyze C‐Fluoromethylation via a CH2F‐Cobalamin Intermediate

Kong, L., Zhang, J., Wang, H., Wei, Z., Wang, W., Hu, J., & Dong, M. (2024) · Angewandte Chemie International Edition · doi:10.1002/anie.202419815 · Cited by 13

Chemical inhibition of a bacterial immune system

Zang, Z., Duncan, O. K., Sabonis, D., Fedorova, I., Shi, Y., Miraj, G., Le, S., Deng, J., Zhu, Y., Cai, Y., et al. (2026) · Cell Host & Microbe · doi:10.1016/j.chom.2026.01.003 · Cited by 14

Tryptophan metabolites at the service of neuroimmune sensing of microbes

Wang, Y., Li, J., Lian, Z., Hao, H., & Zheng, X. (2025) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2025.10.009 · Cited by 10

Intestinal amino acid metabolic response and its roles in inflammatory bowel disease

Niu, Y., Wang, F., Liu, C. H., Liu, Z., & Hu, X. (2025) · Cell Communication and Signaling · doi:10.1186/s12964-025-02622-0 · Cited by 11

Emerging gut microbial glycoside hydrolase inhibitors

Kowalewski, M. E., & Redinbo, M. R. (2025) · RSC Chemical Biology · doi:10.1039/d5cb00050e · Cited by 12

Causal relationships between gut microbiota, plasma metabolites, and HIV infection: insights from Mendelian randomization and mediation analysis

Hu, J., Hu, J., & Han, D. (2024) · Virology Journal · doi:10.1186/s12985-024-02480-1 · Cited by 9

A Small-Molecule Inhibitor of Gut Bacterial Urease Protects the Host from Liver Injury

Richards-Corke, K. C., Jiang, Y., Yeliseyev, V., Zhang, Y., Franzosa, E. A., Wang, Z. A., Abeywardana, M. Y., Cole, P. A., Huttenhower, C., Bry, L., et al. (2025) · ACS Chemical Biology · doi:10.1021/acschembio.3c00556 · Cited by 10

Natural products from the human microbiome: an emergent frontier in organic synthesis and drug discovery

Sengupta, S., Pabbaraja, S., & Mehta, G. (2024) · Organic & Biomolecular Chemistry · doi:10.1039/d4ob00236a · Cited by 9

The phospho-ferrozine assay: a tool to study bacterial redox-active metabolites produced at the plant root

Giacalone, D., Schutt, E., & McRose, D. L. (2024) · Applied and Environmental Microbiology · doi:10.1128/aem.02194-24 · Cited by 7

Microbiota mechanisms in cancer progression and therapy

Zhang, X., Fam, K. T., Dai, T., & Hang, H. C. (2025) · Cell chemical biology · doi:10.1016/j.chembiol.2025.04.005 · Cited by 7

All Roads Lead to Carbinolamine: QM/MM Study of Enzymatic C–N Bond Cleavage in Anaerobic Glycyl Radical Enzyme Choline Trimethylamine-Lyase (CutC)

Hanževački, M., Güven, J. J., Hinchliffe, P., Shaw, J., Mey, A. S. J. S., Fey, N., SPENCER, J. M., & Mulholland, A. J. (2025) · The Journal of Physical Chemistry B · doi:10.1021/acs.jpcb.5c04023 · Cited by 5

Phenotypic high-throughput screening identifies modulators of gut microbial choline metabolism

Woo, A. Y. M., Sandoval-Espínola, W. J., Bollenbach, M., Wong, A., Sakanaka, M., Zhang, Q., Nieto, V., Rey, F. E., & Balskus, E. P. (2026) · mBio · doi:10.1128/mbio.01172-25 · Cited by 4

Cardiovascular–kidney–metabolic syndrome through the lens of gut‑derived uremic toxins

Xu, C., Snelson, M., & Marques, F. Z. (2026) · Gut Microbes · doi:10.1080/19490976.2026.2685906 · Cited by 4

Supplementation and Elimination of Microbiome‐Produced Metabolites in the Treatment of Human Disease

Malogan, J., Hallowell, H. A., Francis, B., & Suez, J. (2025) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.70103 · Cited by 3

Understanding the Role of Gut Microbial Enzyme in CMD

Zhuo, Y., Yu, L., Jiang, C., & Wang, K. (2026) · Circulation Research · doi:10.1161/circresaha.125.326979 · Cited by 3

Role of the gut microbiome in shaping drug response in immunocompromised hosts

Bejaoui, S., D’Amico, F., & Turroni, S. (2026) · Clinical Microbiology and Infection · doi:10.1016/j.cmi.2026.02.026 · Cited by 6

In vivo mechanism of the interaction between trimethylamine lyase expression and glycolytic pathways

Li, Q., Wu, D., Song, Y., Zhang, L., Wang, T., Chen, X., & Zhang, M. (2024) · Food & Function · doi:10.1039/d4fo03809f · Cited by 3

The Gut-Liver Axis in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD): Mechanisms, Microbiome Interactions and Therapeutic Targets

Sahu, P., & Satapathy, T. (2026) · Probiotics and Antimicrobial Proteins · doi:10.1007/s12602-026-11050-6 · Cited by 3

Discovering microbiota functions via chemical probe incorporation for targeted sequencing

Falco, N., & Griffin, M. E. (2024) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2024.102551 · Cited by 2

Beneficial modulation of the gut microbiome by leachates of Penicillium purpurogenum in the presence of clays: A model for the preparation and efficacy of historical Lemnian Earth

Milling, S. W. F., Ijaz, U. Z., Venieri, D., Christidis, G. E., Rattray, N. J. W., Gounaki, I., Andrusaite, A. T., Hareendran, A., Knapp, C. W., Jones, A. X., et al. (2024) · PLoS ONE · doi:10.1371/journal.pone.0313090 · Cited by 1

B12‐Dependent Radical SAM Enzymes Catalyze C‐Fluoromethylation via a CH2F‐Cobalamin Intermediate

Kong, L., Zhang, J., Wang, H., Wei, Z., Wang, W., Hu, J., & Dong, M. (2024) · Angewandte Chemie · doi:10.1002/ange.202419815 · Cited by 1

Eating our way to gut microbiome characterization

Sun, L., Lin, J., & Jiang, C. (2023) · Cell Host & Microbe · doi:10.1016/j.chom.2023.06.003

Desulfovibrio ‐Hydrogen Sulfide Mediates Capsaicin‐Induced Oxidative Stress and Gut Inflammation via TXNIP/NLRP3 Pathway

Zhu, L., Feng, X., Lu, X., Han, G., Zou, J., Dong, Z., Luo, T., Jin, J., Zhao, M., Ji, X., et al. (2026) · Food Bioengineering · doi:10.1002/fbe2.70047

Oral hydrogel systems in lower gastrointestinal disorders: From disease-based therapy to microbiota-guided design

Wu, H., Tian, J., Luo, W., Liu, J., Chen, Y., Yang, K., Zhou, J., Li, J., Yang, S. M., Zhang, Y., et al. (2026) · Materials Today Bio · doi:10.1016/j.mtbio.2026.103357 · Cited by 1

Modulating the human gut microbiome-host system: a new drug discovery paradigm

Colmenarejo, G. (2026) · Frontiers in Drug Discovery · doi:10.3389/fddsv.2026.1898583

The microbiota-host metabolic axis in cervical cancer: from homeostatic disruption to mechanisms of therapy resistance

He, Y., Zhao, Y., Ju, S., Zhou, P., Si, J., Pan, Y., & Jiang, Y. (2026) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2026.1890330

Smart-delivery systems for intestinal mucosal homeostasis: From barrier penetration to precision regulation

Shi, M., Li, X., Li, J., Huang, Y., Wang, W., Di, L., Chen, J., & Wang, R. (2026) · Journal of Controlled Release · doi:10.1016/j.jconrel.2026.115258

Drugging the gut microbiota: toward rational modulation of bacterial composition in the gut

Altamura, F., Maurice, C. F., & Castagner, B. (2019) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2019.09.005 · Cited by 17

Drugging the microbiome: targeting small microbiome molecules

Sharma, S., Hegde, P. V., Panda, S., Orimoloye, M. O., & Aldrich, C. C. (2022) · Current Opinion in Microbiology · doi:10.1016/j.mib.2022.102234 · Cited by 2

Probing and manipulating the gut microbiome with chemistry and chemical tools

Mantravadi, P. K., Kovi, B. S., Reddy, S. R., Pandian, G. N., Kalesh, K., & Parthasarathy, A. (2025) · Gut Microbiome · doi:10.1017/gmb.2025.4 · Cited by 4

Discovery of small molecule enzyme inhibitors from gut microbes as potential antiinflammatory and anticancer agents

Stierle, A. A. (2013) · Journal of Postgenomics Drug & Biomarker Development

Deciphering Human Microbiota–Host Chemical Interactions

Silpe, J. E., & Balskus, E. P. (2020) · ACS Central Science · doi:10.1021/acscentsci.0c01030 · Cited by 43