Bifidobacterium animalis subsp. lactis V9 overcomes CYFRA 21-1–linked immunochemotherapy resistance in NSCLC via microbial metabolites
Menée à l'aide de modèles murins, d'échantillons fécaux et d'échantillons sériques issus de patients atteints d'un cancer du poumon non à petites cellules de stade avancé traité par immunochimiothérapie puis confirmée par essai clinique randomisé sur 30 patients, cette étude met en évidence une association entre un niveau élevé du fragment de la cytokératine 19 (CYFRA 21-1) et une dysbiose intestinale puis démontre que les métabolites de la bactérie Bifidobacterium animalis lactis V9 lèvent la résistance thérapeutique liée à CYFRA 21-1
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–small cell lung cancer (NSCLC) correlates with gut dysbiosis, including Bifidobacterium animalis 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 B. animalis subsp. lactis 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 = 30), adjunctive B. lactis 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 B. animalis and elevated quinaldic acid/catechol (area under the curve = 0.73/0.82). These findings suggest CYFRA 21-1 may identify a modifiable, microbiome-linked state of treatment resistance.
Science Advances , résumé, 2026