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REVIEW article

Front. Microbiol.

Sec. Microbiotechnology

Volume 16 - 2025 | doi: 10.3389/fmicb.2025.1610029

This article is part of the Research TopicSynthetic Biology for Non-Model MicrobesView all 6 articles

Microbiome Engineering: Unlocking Therapeutic Potential in Inflammatory Bowel Disease

Provisionally accepted
Chen KongChen Kong1Long-Bin HuangLong-Bin Huang1Mei-feng YangMei-feng Yang2Ning-Ning YueNing-Ning Yue1DUO LUODUO LUO2Yuan ZhangYuan Zhang3Cheng-mei TianCheng-mei Tian1Yang SongYang Song1*Dao-Ru WeiDao-Ru Wei1*Rui-Yue ShiRui-Yue Shi1*Yujie LiangYujie Liang4*Jun YaoJun Yao1*Li-sheng WangLi-sheng Wang1De-feng LiDe-feng Li1*
  • 1Shenzhen People's Hospital, Jinan University, Shenzhen, China
  • 2Guangzhou First People's Hospital, Guangzhou, Guangdong Province, China
  • 3Department of Medical Administration, Huizhou Institute of Occupational Diseases Control and Prevention, Huizhou, Guangdong Province, China
  • 4Shenzhen KangNing Hospital, Shenzhen, Guangdong Province, China

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The human gut microbiome, traditionally linked to infectious diseases, is now recognized as a hub of non-pathogenic microorganisms that play pivotal roles in host communication and homeostasis. Advances in microbiome engineering have enabled the design of "smart" living therapeutics for inflammatory bowel disease (IBD), leveraging engineered symbiotic bacteria, yeasts, and bacteriophages. This review synthesizes recent progress in reprogramming microbes using synthetic biology tools, emphasizing their capacity to sense pathological signals and deliver targeted therapies. We critically evaluate three key approaches: synthetic gene circuits in bacteria for precision drug delivery, phage-mediated modulation of dysbiotic microbiota, and yeast-based systems for metabolic intervention (e.g., butyrate production). Challenges in biocontainment, genetic stability, and clinical translation are discussed, alongside emerging strategies such as outer membrane vesicles (OMVs) for immunomodulation. By distilling these advances, we highlight a roadmap for translating engineered microbes into safe and effective IBD therapies.

Keywords: microbiome, Synthetic Biology, inflammatory bowel disease, extracellular vesicles, therapy

Received: 24 Apr 2025; Accepted: 29 Jul 2025.

Copyright: © 2025 Kong, Huang, Yang, Yue, LUO, Zhang, Tian, Song, Wei, Shi, Liang, Yao, Wang and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Yang Song, Shenzhen People's Hospital, Jinan University, Shenzhen, China
Dao-Ru Wei, Shenzhen People's Hospital, Jinan University, Shenzhen, China
Rui-Yue Shi, Shenzhen People's Hospital, Jinan University, Shenzhen, China
Yujie Liang, Shenzhen KangNing Hospital, Shenzhen, Guangdong Province, China
Jun Yao, Shenzhen People's Hospital, Jinan University, Shenzhen, China
De-feng Li, Shenzhen People's Hospital, Jinan University, Shenzhen, China

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

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