Bifidobacterium animalis subsp. lactis V9 Overcomes CYFRA 21-1-Linked Immunochemotherapy Resistance in NSCLC via Microbial Metabolites

ABSTRACT:

Elevated serum cytokeratin 19 fragment (CYFRA 21-1) marks aggressive disease

and poor response to immunochemotherapy in advanced non-small cell lung cancer

(NSCLC), but its link to gut microbiome dysfunction remains unclear. We show that

high CYFRA 21-1 levels correlate with depletion of Bifidobacterium animalis and

antitumor metabolites. Gut microbial metabolites from these patients suppress

immunochemotherapy efficacy in mice through dysregulated tryptophan and

phenylalanine metabolism. Adjuvant Bifidobacterium animalis subsp. lactis V9 (B.

lactis V9) restores gut microbial balance and increased quinaldic acid and catechol,

which enhance antitumor immunity and induce tumor cell death via caspase-dependent

apoptosis and ferroptosis. This benefit transfers via fecal supernatant, independent of

bacterial colonization. In a randomized, double-blind, placebo-controlled trial (n = 30),

adjunctive B. lactis V9 improves objective response rate (47% vs. 33%), disease control

rate (87% vs. 67%), and prolongs progression-free survival in responders, establishing

a metabolite-mediated strategy to overcome treatment resistance in high-CYFRA 21-1

NSCLC.

INSTRUMENT(S): Liquid Chromatography MS - negative - reverse phase, Liquid Chromatography MS - positive - reverse phase

PROVIDER: MTBLS13296 | MetaboLights | 2026-07-21

REPOSITORIES: MetaboLights