{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T22:19:20Z","timestamp":1789510760214,"version":"build-2803163510"},"reference-count":175,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T00:00:00Z","timestamp":1781654400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"PRIMA Programme (Partnership for Research and Innovation in the Mediterranean Area","award":["CUP H93C22000950001; HORIZON-HLTH-2022-STAYHLTH-01-05; Project 101080329"],"award-info":[{"award-number":["CUP H93C22000950001; HORIZON-HLTH-2022-STAYHLTH-01-05; Project 101080329"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>The gut microbiota is increasingly examined as a therapeutic target because it contributes to epithelial barrier integrity, microbial metabolite production, bile acid transformation, immune regulation, and communication between the gut and distant organs. This structured narrative review synthesizes evidence on microbiota involvement in metabolic, gastrointestinal, hepatic, cancer, and neuroimmune conditions, including MASLD\/MASH, inflammatory bowel disease, irritable bowel syndrome, obesity, type 2 diabetes, hypertension, colorectal cancer, Parkinson\u2019s disease, and autism spectrum disorder. Across these conditions, microbiome findings are biologically plausible but heterogeneous. Many associations are shaped by diet, geography, medication exposure, host genetics, disease stage, sampling methods, and analytical pipelines. Microbial alterations should therefore be interpreted as context-dependent signals and candidate modifiers rather than universal causal markers. Conventional microbiota targeted strategies include diet, physical activity, prebiotics, probiotics, synbiotics, postbiotics, and fecal microbiota transplantation. These approaches are clinically familiar, but their effects are often broad, host specific, strain dependent, and difficult to assign to one mechanism. Fecal microbiota transplantation has the clearest clinical role in recurrent Clostridioides difficile infection, while evidence for most other indications remains inconsistent. Engineered microbial therapeutics offer greater experimental precision through signal sensing, payload delivery, metabolic modulation, and genetic circuit design. However, most evidence remains preclinical or early translational. Progress requires stronger human trials, standardized methods, mechanistic validation, safety monitoring, ecological containment, transparent reporting, and proportionate regulation.<\/jats:p>","DOI":"10.3390\/nu18121958","type":"journal-article","created":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T15:11:22Z","timestamp":1781709082000},"page":"1958","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Targeting the Human Gut Microbiota\u2014Between Conventional Therapy and Precision Genetic Engineering"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-3405-4482","authenticated-orcid":false,"given":"Naomi-Adina","family":"Ciurea","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, \u201cGeorge Emil Palade\u201d University of Medicine, Pharmacy, Science and Technology of Targu Mures, 540139 Targu Mures, Romania"},{"name":"Doctoral School of Medicine and Pharmacy, \u201cGeorge Emil Palade\u201d University of Medicine, Pharmacy, Sciences and Technology of Targu Mures, 38 Gheorghe Marinescu Street, 540139 Targu Mures, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3190-331X","authenticated-orcid":false,"given":"Laura","family":"Mahdi","sequence":"additional","affiliation":[{"name":"Clinica Medica A. Murri, Department of Precision and Regenerative Medicine and Ionian Area (DiMePre-J), University of Bari Aldo Moro, Piazzale G. Cesare 11, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annarita","family":"Graziani","sequence":"additional","affiliation":[{"name":"Institut AllergoSan Pharmazeutische Produkte Forschungs- und Vertriebs GmbH, 8055 Graz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agostino","family":"Di Ciaula","sequence":"additional","affiliation":[{"name":"Clinica Medica A. Murri, Department of Precision and Regenerative Medicine and Ionian Area (DiMePre-J), University of Bari Aldo Moro, Piazzale G. Cesare 11, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5359-1471","authenticated-orcid":false,"given":"Piero","family":"Portincasa","sequence":"additional","affiliation":[{"name":"Clinica Medica A. 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