{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T05:47:58Z","timestamp":1782366478129,"version":"3.54.5"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T00:00:00Z","timestamp":1782345600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:p>The homeostasis of the human microbiome relies on \u201ccolonization resistance\u201d governed by complex ecological rules. However, severe perturbations such as broad-spectrum antibiotics can dismantle this defense, shifting the microbial community into a \u201cdysbiotic trap\u201d driven by pathogen niche construction\u2014an alternative stable state that is notoriously difficult to spontaneously reverse. This ecological mechanism explains the frequent failure of empirical therapies like fecal microbiota transplantation (FMT) and blind probiotic supplementation. Crucially, local ecological collapse triggers systemic cascades via the \u201cgut-lung axis.\u201d The depletion of core gut metabolites, such as short-chain fatty acids, impairs the metabolic reprogramming and antimicrobial capacity of distal alveolar macrophages. This cascade drastically increases host susceptibility to respiratory infections. To break this clinical deadlock, microbiome medicine must transition from \u201cempirical transplantation\u201d to \u201crational microbiome engineering.\u201d This review systematically outlines the core pillars of this translational framework: achieving \u201cprecision niche clearing\u201d via targeted bacteriophages; capturing optimal intervention windows to harness \u201cpriority effects\u201d; and ultimately engrafting \u201csynthetic microbial consortia\u201d (SMCs) rationally designed upon metabolic cross-feeding principles. This strategy offers a promising avenue to durably shatter the dysbiotic deadlock and restore host immune homeostasis across the gut and systemic levels.<\/jats:p>","DOI":"10.3389\/fmicb.2026.1871211","type":"journal-article","created":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T05:30:43Z","timestamp":1782365443000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Translating priority effects and niche engineering into rational microbiome therapeutics across the gut-lung axis"],"prefix":"10.3389","volume":"17","author":[{"given":"Huimin","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Pediatric Surgery, The Second Hospital of Jilin University","place":["Changchun, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery, The Second Hospital of Jilin University","place":["Changchun, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Bai","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery, The Second Hospital of Jilin University","place":["Changchun, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijie","family":"Yu","sequence":"additional","affiliation":[{"name":"Lishu County Traditional Chinese Medicine Hospital","place":["Siping, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ye","family":"Gu","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery, The Second Hospital of Jilin University","place":["Changchun, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,25]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1038\/s41579-022-00833-7","article-title":"Microbiota-mediated colonization resistance: Mechanisms and regulation.","volume":"21","author":"Caballero-Flores","year":"2023","journal-title":"Nat. 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