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Adv."],"published-print":{"date-parts":[[2026,9,4]]},"abstract":"<jats:p>\n                    Gut dysbiosis drives therapeutic resistance, yet the relationships among typical tumor markers, gut microbiota, and treatment efficacy remain poorly defined. Here, elevated serum CYFRA 21-1 in advanced non\u2013small cell lung cancer (NSCLC) correlates with gut dysbiosis, including\n                    <jats:italic toggle=\"yes\">Bifidobacterium animalis<\/jats:italic>\n                    depletion and reduced immunomodulatory metabolites. Fecal supernatant from patients with high-CYFRA attenuated immunochemotherapy efficacy in tumor-bearing mice, linked to disrupted tryptophan and phenylalanine metabolism. Adjuvant\n                    <jats:italic toggle=\"yes\">B. animalis<\/jats:italic>\n                    subsp.\n                    <jats:italic toggle=\"yes\">lactis<\/jats:italic>\n                    V9 enhanced tumor control and antitumor immunity, coinciding with elevated quinaldic acid and catechol, metabolites associated with caspase-dependent apoptosis and ferroptosis. Cell-free fecal supernatant transferred antitumor effects, independent of bacterial colonization. In a randomized, double-blind, placebo-controlled pilot trial (\n                    <jats:italic toggle=\"yes\">n<\/jats:italic>\n                    \u00a0=\u00a030), adjunctive\n                    <jats:italic toggle=\"yes\">B. lactis<\/jats:italic>\n                    V9 associated with a higher objective response rate (47% versus 33%), disease control rate (87% versus 67%), and prolonged progression-free survival in responders, who exhibited enriched\n                    <jats:italic toggle=\"yes\">B. animalis<\/jats:italic>\n                    and elevated quinaldic acid\/catechol (area under the curve\u00a0=\u00a00.73\/0.82). These findings suggest CYFRA 21-1 may identify a modifiable, microbiome-linked state of treatment resistance.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.aeg8202","type":"journal-article","created":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T17:59:26Z","timestamp":1788371966000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["<i>Bifidobacterium animalis<\/i>\n                    subsp.\n                    <i>lactis<\/i>\n                    V9 overcomes CYFRA 21-1\u2013linked immunochemotherapy resistance in NSCLC via microbial metabolites"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5113-6691","authenticated-orcid":true,"given":"Cuijiao","family":"Feng","sequence":"first","affiliation":[{"name":"Inner Mongolia Key Laboratory of Dairy Biotechnology and Engineering, Inner Mongolia Agricultural University, Hohhot, China."},{"name":"Key Laboratory of Dairy 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Biotechnology and Engineering, Inner Mongolia Agricultural University, Hohhot, China."},{"name":"Key Laboratory of Dairy Products Processing, Ministry of Agriculture and Rural Affairs, Inner Mongolia Agricultural University, Hohhot, China."},{"name":"Key Laboratory of Dairy Biotechnology and Engineering, Ministry of Education, Inner Mongolia Agricultural University, Hohhot, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lai-Yu","family":"Kwok","sequence":"additional","affiliation":[{"name":"Inner Mongolia Key Laboratory of Dairy Biotechnology and Engineering, Inner Mongolia Agricultural University, Hohhot, China."},{"name":"Key Laboratory of Dairy Products Processing, Ministry of Agriculture and Rural Affairs, Inner Mongolia Agricultural University, Hohhot, China."},{"name":"Key Laboratory of Dairy Biotechnology and Engineering, Ministry of Education, Inner Mongolia Agricultural University, Hohhot, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cong","family":"Liu","sequence":"additional","affiliation":[{"name":"Medical Oncology, Inner Mongolia People\u2019s Hospital, Hohhot, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang","family":"Li","sequence":"additional","affiliation":[{"name":"Medical Oncology, Inner Mongolia People\u2019s Hospital, Hohhot, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-5680-8563","authenticated-orcid":true,"given":"Li","family":"Dong","sequence":"additional","affiliation":[{"name":"Medical Oncology, Inner Mongolia People\u2019s Hospital, Hohhot, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7605-2048","authenticated-orcid":true,"given":"Zhihong","family":"Sun","sequence":"additional","affiliation":[{"name":"Inner Mongolia Key Laboratory of Dairy Biotechnology and Engineering, Inner 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