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The gut\u2013lung axis and microbial metabolites, such as short-chain fatty acids (SCFAs), have emerged as modulators of lung inflammation. We investigated the therapeutic effects of\n                    <jats:italic>Lactobacillus fermentum<\/jats:italic>\n                    HEM20792 (LF), identified through a colon mimetic personalized pharmaceutical meta-analytical screening (PMAS) platform using fecal samples from severe COPD patients. LF and\n                    <jats:italic>Lactobacillus sakei<\/jats:italic>\n                    HEM20224 (LS) were orally administered to smoke-exposed mice, followed by lung function testing, histopathology, RNA sequencing, single-cell transcriptomics, and fecal microbiome\/SCFAs analyses. LF attenuated emphysematous changes, improved compliance, and reduced macrophage and IL-17+ lymphocyte infiltration. Single-cell analysis showed restoration of alveolar macrophages and reduction of pathogenic C1q\n                    <jats:sup>+<\/jats:sup>\n                    macrophages, while transcriptomics revealed normalization of NF-\u03baB and arachidonic acid pathways and attenuation of IL-17\u2013 and SPP1-associated signaling. LF also increased fecal SCFAs levels. These findings provide preclinical evidence for LF as a promising microbiome-based therapeutic candidate for COPD.\n                  <\/jats:p>","DOI":"10.1038\/s41522-026-00978-w","type":"journal-article","created":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T14:55:10Z","timestamp":1776178510000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["A colon mimetic screening approach reveals Lactobacillus fermentum as a microbiome-based therapy for COPD"],"prefix":"10.1038","volume":"12","author":[{"given":"Na Hyun","family":"Kim","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaeik","family":"Oh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jang Ho","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sunyoung","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eun Sung","family":"Jung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong Ho","family":"Suh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hye-Ji","family":"Kang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bobae","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hye-Shin","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hae Rim","family":"Jung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heeseo","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I Na Rae","family":"Yun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yosep","family":"Ji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sung-Yup","family":"Cho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sei Won","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,14]]},"reference":[{"key":"978_CR1","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1111\/resp.12660","volume":"21","author":"JL L\u00f3pez-Campos","year":"2016","unstructured":"L\u00f3pez-Campos, J. 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