{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T00:58:08Z","timestamp":1789001888815,"version":"build-2803163510"},"reference-count":178,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T00:00:00Z","timestamp":1779408000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["32460015"],"award-info":[{"award-number":["32460015"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"award":["32460015"],"award-info":[{"award-number":["32460015"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Guangxi Special Project for Supporting the Cultivation of Maritime Economic Talents"},{"name":"Strengthening Foundations\u201d Action Plan of Guangxi Science and Technology Plan Project","award":["2025LT0103004"],"award-info":[{"award-number":["2025LT0103004"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>The gut microbiome, often termed the human \u201csecond genome\u201d, profoundly influences host physiology through metabolic interactions, immune modulation, and gut\u2013brain axis signaling. Dysbiosis is implicated in the pathogenesis of obesity, inflammatory bowel disease (IBD), malignancies, and neuropsychiatric disorders. However, traditional gut microbiota interventions, such as probiotic supplementation and fecal microbiota transplantation (FMT), still exhibit significant limitations in precision therapeutics. Probiotic intervention fails to achieve precise regulation at the strain or genetic level, and although FMT demonstrates definitive efficacy against recurrent Clostridioides difficile infection (rCDI), its therapeutic outcomes and safety profiles show marked interindividual variability in ulcerative colitis (UC), metabolic syndrome, and other diseases, with insufficient treatment specificity to meet the practical demands of clinical precision intervention. Recent advancements in genome editing technologies, particularly Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)\u2013CRISPR-associated (Cas) proteins systems and base editors, have enabled targeted functional manipulation of specific gut commensals and optimization of community architectures. These engineered strategies, combined with sophisticated delivery systems, demonstrate substantial potential in disease treatment, diagnostic monitoring, and immune modulation. This review systematically examines core editing methodologies, innovative delivery platforms, and targeted design strategies, elucidating their applications in metabolic disorders, IBD, cancer immunotherapy, and neuropsychiatric conditions. We critically analyze current technical bottlenecks and biosafety concerns while prospecting future directions, including in situ editing, artificial intelligence (AI)-driven design, and personalized engineering. Collectively, these insights aim to facilitate the clinical translation of gut microbiome engineering from bench to bedside.<\/jats:p>","DOI":"10.3390\/microorganisms14061174","type":"journal-article","created":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T16:06:08Z","timestamp":1779465968000},"page":"1174","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Engineering the Gut Microbiome: Emerging Genome-Editing Strategies and Therapeutic Applications"],"prefix":"10.3390","volume":"14","author":[{"given":"Liu","family":"Wu","sequence":"first","affiliation":[{"name":"College of Animal Science and Technology, Guangxi University, Nanning 530004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zongyan","family":"Li","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Guangxi University, Nanning 530004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinxuan","family":"Zhu","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Guangxi University, Nanning 530004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhigang","family":"Sun","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Guangxi University, Nanning 530004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lujun","family":"Yan","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Guangxi University, Nanning 530004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingzhan","family":"Luo","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Guangxi University, Nanning 530004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huahai","family":"Chen","sequence":"additional","affiliation":[{"name":"Guangxi Academy of Marine Sciences, Guangxi Academy of Sciences, Nanning 530007, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6866-5525","authenticated-orcid":false,"given":"Yeshi","family":"Yin","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology, Guangxi University, Nanning 530004, China"},{"name":"Guangxi Key Laboratory of Animal Reproduction, Breeding and Disease Control, Nanning 530004, China"},{"name":"Guangxi Zhuang Autonomous Region Engineering Research Center of Veterinary Biologics, Nanning 530004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Krishnamurthy, H.K., Pereira, M., Bosco, J., George, J., Jayaraman, V., Krishna, K., Wang, T., Bei, K., and Rajasekaran, J.J. 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