---
title: "B. animalis subsp. lactis V9 reverses CYFRA 21-1–linked immunochemotherapy resistance in NSCLC via"
id: "pubmed-42685222"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42685222"
content_type: "clinical_feed_article"
specialty: "Critical Care"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42685222/"
doi: "10.1126/sciadv.aeg8202"
published_at: "2026-09-04T00:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# B. animalis subsp. lactis V9 reverses CYFRA 21-1–linked immunochemotherapy resistance in NSCLC via
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42685222
- **Specialty:** [Critical Care](https://medichelpline.com/clinical-feed/critical-care.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42685222/)
- **DOI:** [10.1126/sciadv.aeg8202](https://doi.org/10.1126%2Fsciadv.aeg8202)
- **Published At:** 2026-09-04T00:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- Elevated serum **CYFRA 21-1** in advanced non–small cell lung cancer (**NSCLC**) patients is associated with **gut dysbiosis**, including depletion of **Bifidobacterium animalis** and reduced levels of immunomodulatory metabolites. - Fecal supernatant from patients with high CYFRA 21-1 reduced the efficacy of immunochemotherapy when transferred to tumor-bearing mice, implicating soluble microbial products rather than live bacteria alone. - Disrupted **tryptophan** and **phenylalanine** metabolic pathways were linked to the attenuated treatment response observed with high-CYFRA fecal supernatant. - Adjuvant **Bifidobacterium animalis subsp. lactis V9** improved tumor control and antitumor immune responses in experimental models, coinciding with increased levels of **quinaldic acid** and **catechol**. - The metabolites quinaldic acid and catechol were associated with mechanisms of cell death, specifically caspase-dependent apoptosis and **ferroptosis**, suggesting metabolite-mediated tumor suppression. - Cell-free fecal supernatant from treated donors could transfer antitumor effects to recipients without requiring bacterial colonization, indicating that microbial metabolites alone can modulate therapy response. - In a randomized, double-blind, placebo-controlled pilot clinical trial (n = 30), adjunctive **B. lactis V9** was associated with a higher objective response rate (47% vs 33%) and altered measures of disease control reported in the abstract; additional trial details and complete outcomes were not reported in the provided source excerpt. - Overall, the study links a circulating tumor marker (**CYFRA 21-1**), gut microbial composition, and microbial metabolites to immunochemotherapy resistance in NSCLC and identifies **B. lactis V9** and specific metabolites as potential modulators of therapeutic efficacy.
## Clinical Analysis & Structured Key Points
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Epub 2026 Sep 2. # _Bifidobacterium animalis_ subsp. _lactis_ V9 overcomes CYFRA 21-1-linked immunochemotherapy resistance in NSCLC via microbial metabolites [Cuijiao Feng](https://pubmed.ncbi.nlm.nih.gov/?term=Feng+C&cauthor_id=42685222)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42685222/#full-view-affiliation-1 "Inner Mongolia Key Laboratory of Dairy Biotechnology and Engineering, Inner Mongolia Agricultural University, Hohhot, China.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42685222/#full-view-affiliation-2 "Key Laboratory of Dairy Products Processing, Ministry of Agriculture and Rural Affairs, Inner Mongolia Agricultural University, Hohhot, China.")[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42685222/#full-view-affiliation-3 "Key Laboratory of Dairy Biotechnology and Engineering, Ministry of Education, Inner Mongolia Agricultural University, Hohhot, China."), [Guangqi Gao](https://pubmed.ncbi.nlm.nih.gov/?term=Gao+G&cauthor_id=42685222)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42685222/#full-view-affiliation-1 "Inner Mongolia Key Laboratory of Dairy Biotechnology and Engineering, Inner Mongolia Agricultural University, Hohhot, China.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42685222/#full-view-affiliation-2 "Key Laboratory of Dairy Products Processing, Ministry of Agriculture and Rural Affairs, Inner Mongolia Agricultural University, Hohhot, China.")[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42685222/#full-view-affiliation-3 "Key Laboratory of Dairy Biotechnology and Engineering, Ministry of Education, Inner Mongolia Agricultural University, Hohhot, China."), [Qiuwen He](https://pubmed.ncbi.nlm.nih.gov/?term=He+Q&cauthor_id=42685222)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42685222/#full-view-affiliation-1 "Inner Mongolia Key Laboratory of Dairy Biotechnology and Engineering, Inner Mongolia Agricultural University, Hohhot, China.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42685222/#full-view-affiliation-2 "Key Laboratory of Dairy Products Processing, Ministry of Agriculture and Rural Affairs, Inner Mongolia Agricultural University, Hohhot, China.")[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42685222/#full-view-affiliation-3 "Key Laboratory of Dairy Biotechnology and Engineering, Ministry of Education, Inner Mongolia Agricultural University, Hohhot, China."), [Lai-Yu Kwok](https://pubmed.ncbi.nlm.nih.gov/?term=Kwok+LY&cauthor_id=42685222)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42685222/#full-view-affiliation-1 "Inner Mongolia Key Laboratory of Dairy Biotechnology and Engineering, Inner Mongolia Agricultural University, Hohhot, China.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42685222/#full-view-affiliation-2 "Key Laboratory of Dairy Products Processing, Ministry of Agriculture and Rural Affairs, Inner Mongolia Agricultural University, Hohhot, China.")[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42685222/#full-view-affiliation-3 "Key Laboratory of Dairy Biotechnology and Engineering, Ministry of Education, Inner Mongolia Agricultural University, Hohhot, China."), [Cong Liu](https://pubmed.ncbi.nlm.nih.gov/?term=Liu+C&cauthor_id=42685222)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42685222/#full-view-affiliation-4 "Medical Oncology, Inner Mongolia People's Hospital, Hohhot, China."), [Chang Li](https://pubmed.ncbi.nlm.nih.gov/?term=Li+C&cauthor_id=42685222)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42685222/#full-view-affiliation-4 "Medical Oncology, Inner Mongolia People's Hospital, Hohhot, China."), [Li Dong](https://pubmed.ncbi.nlm.nih.gov/?term=Dong+L&cauthor_id=42685222)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42685222/#full-view-affiliation-4 "Medical Oncology, Inner Mongolia People's Hospital, Hohhot, China."), [Zhihong Sun](https://pubmed.ncbi.nlm.nih.gov/?term=Sun+Z&cauthor_id=42685222)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42685222/#full-view-affiliation-1 "Inner Mongolia Key Laboratory of Dairy Biotechnology and Engineering, Inner Mongolia Agricultural University, Hohhot, China.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42685222/#full-view-affiliation-2 "Key Laboratory of Dairy Products Processing, Ministry of Agriculture and Rural Affairs, Inner Mongolia Agricultural University, Hohhot, China.")[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42685222/#full-view-affiliation-3 "Key Laboratory of Dairy Biotechnology and Engineering, Ministry of Education, Inner Mongolia Agricultural University, Hohhot, China."), [Heping Zhang](https://pubmed.ncbi.nlm.nih.gov/?term=Zhang+H&cauthor_id=42685222)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42685222/#full-view-affiliation-1 "Inner Mongolia Key Laboratory of Dairy Biotechnology and Engineering, Inner Mongolia Agricultural University, Hohhot, China.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42685222/#full-view-affiliation-2 "Key Laboratory of Dairy Products Processing, Ministry of Agriculture and Rural Affairs, Inner Mongolia Agricultural University, Hohhot, China.")[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42685222/#full-view-affiliation-3 "Key Laboratory of Dairy Biotechnology and Engineering, Ministry of Education, Inner Mongolia Agricultural University, Hohhot, China.") Affiliations Expand ### Affiliations * 1 Inner Mongolia Key Laboratory of Dairy Biotechnology and Engineering, Inner Mongolia Agricultural University, Hohhot, China. * 2 Key Laboratory of Dairy Products Processing, Ministry of Agriculture and Rural Affairs, Inner Mongolia Agricultural University, Hohhot, China. * 3 Key Laboratory of Dairy Biotechnology and Engineering, Ministry of Education, Inner Mongolia Agricultural University, Hohhot, China. * 4 Medical Oncology, Inner Mongolia People's Hospital, Hohhot, China. * PMID: **42685222** * PMCID: [ PMC13537245 ](https://pmc.ncbi.nlm.nih.gov/articles/PMC13537245/) * DOI: [ 10.1126/sciadv.aeg8202 ](https://doi.org/10.1126/sciadv.aeg8202) Item in Clipboard Randomized Controlled Trial # _Bifidobacterium animalis_ subsp. _lactis_ V9 overcomes CYFRA 21-1-linked immunochemotherapy resistance in NSCLC via microbial metabolites Cuijiao Feng et al. Sci Adv. 2026. Show details Display options Display options Format Abstract PubMed PMID Sci Adv Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Sci+Adv%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Sci+Adv%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42685222/) . 2026 Sep 4;12(36):eaeg8202. doi: 10.1126/sciadv.aeg8202. Epub 2026 Sep 2. ### Authors [Cuijiao Feng](https://pubmed.ncbi.nlm.nih.gov/?term=Feng+C&cauthor_id=42685222)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42685222/#short-view-affiliation-1 "Inner Mongolia Key Laboratory of Dairy Biotechnology and Engineering, Inner Mongolia Agricultural University, Hohhot, China.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42685222/#short-view-affiliation-2 "Key Laboratory of Dairy Products Processing, Ministry of Agriculture and Rural Affairs, Inner Mongolia Agricultural University, Hohhot, China.")[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42685222/#short-view-affiliation-3 "Key Laboratory of Dairy Biotechnology and Engineering, Ministry of Education, Inner Mongolia Agricultural University, Hohhot, China."), [Guangqi Gao](https://pubmed.ncbi.nlm.nih.gov/?term=Gao+G&cauthor_id=42685222)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42685222/#short-view-affiliation-1 "Inner Mongolia Key Laboratory of Dairy Biotechnology and Engineering, Inner Mongolia Agricultural University, Hohhot, China.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42685222/#short-view-affiliation-2 "Key Laboratory of Dairy Products Processing, Ministry of Agriculture and Rural Affairs, Inner Mongolia Agricultural University, Hohhot, China.")[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42685222/#short-view-affiliation-3 "Key Laboratory of Dairy Biotechnology and Engineering, Ministry of Education, Inner Mongolia Agricultural University, Hohhot, China."), [Qiuwen He](https://pubmed.ncbi.nlm.nih.gov/?term=He+Q&cauthor_id=42685222)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42685222/#short-view-affiliation-1 "Inner Mongolia Key Laboratory of Dairy Biotechnology and Engineering, Inner Mongolia Agricultural University, Hohhot, China.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42685222/#short-view-affiliation-2 "Key Laboratory of Dairy Products Processing, Ministry of Agriculture and Rural Affairs, Inner Mongolia Agricultural University, Hohhot, China.")[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42685222/#short-view-affiliation-3 "Key Laboratory of Dairy Biotechnology and Engineering, Ministry of Education, Inner Mongolia Agricultural University, Hohhot, China."), [Lai-Yu Kwok](https://pubmed.ncbi.nlm.nih.gov/?term=Kwok+LY&cauthor_id=42685222)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42685222/#short-view-affiliation-1 "Inner Mongolia Key Laboratory of Dairy Biotechnology and Engineering, Inner Mongolia Agricultural University, Hohhot, China.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42685222/#short-view-affiliation-2 "Key Laboratory of Dairy Products Processing, Ministry of Agriculture and Rural Affairs, Inner Mongolia Agricultural University, Hohhot, China.")[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42685222/#short-view-affiliation-3 "Key Laboratory of Dairy Biotechnology and Engineering, Ministry of Education, Inner Mongolia Agricultural University, Hohhot, China."), [Cong Liu](https://pubmed.ncbi.nlm.nih.gov/?term=Liu+C&cauthor_id=42685222)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42685222/#short-view-affiliation-4 "Medical Oncology, Inner Mongolia People's Hospital, Hohhot, China."), [Chang Li](https://pubmed.ncbi.nlm.nih.gov/?term=Li+C&cauthor_id=42685222)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42685222/#short-view-affiliation-4 "Medical Oncology, Inner Mongolia People's Hospital, Hohhot, China."), [Li Dong](https://pubmed.ncbi.nlm.nih.gov/?term=Dong+L&cauthor_id=42685222)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42685222/#short-view-affiliation-4 "Medical Oncology, Inner Mongolia People's Hospital, Hohhot, China."), [Zhihong Sun](https://pubmed.ncbi.nlm.nih.gov/?term=Sun+Z&cauthor_id=42685222)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42685222/#short-view-affiliation-1 "Inner Mongolia Key Laboratory of Dairy Biotechnology and Engineering, Inner Mongolia Agricultural University, Hohhot, China.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42685222/#short-view-affiliation-2 "Key Laboratory of Dairy Products Processing, Ministry of Agriculture and Rural Affairs, Inner Mongolia Agricultural University, Hohhot, China.")[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42685222/#short-view-affiliation-3 "Key Laboratory of Dairy Biotechnology and Engineering, Ministry of Education, Inner Mongolia Agricultural University, Hohhot, China."), [Heping Zhang](https://pubmed.ncbi.nlm.nih.gov/?term=Zhang+H&cauthor_id=42685222)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42685222/#short-view-affiliation-1 "Inner Mongolia Key Laboratory of Dairy Biotechnology and Engineering, Inner Mongolia Agricultural University, Hohhot, China.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42685222/#short-view-affiliation-2 "Key Laboratory of Dairy Products Processing, Ministry of Agriculture and Rural Affairs, Inner Mongolia Agricultural University, Hohhot, China.")[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42685222/#short-view-affiliation-3 "Key Laboratory of Dairy Biotechnology and Engineering, Ministry of Education, Inner Mongolia Agricultural University, Hohhot, China.") ### Affiliations * 1 Inner Mongolia Key Laboratory of Dairy Biotechnology and Engineering, Inner Mongolia Agricultural University, Hohhot, China. * 2 Key Laboratory of Dairy Products Processing, Ministry of Agriculture and Rural Affairs, Inner Mongolia Agricultural University, Hohhot, China. * 3 Key Laboratory of Dairy Biotechnology and Engineering, Ministry of Education, Inner Mongolia Agricultural University, Hohhot, China. * 4 Medical Oncology, Inner Mongolia People's Hospital, Hohhot, China. * PMID: **42685222** * PMCID: [ PMC13537245 ](https://pmc.ncbi.nlm.nih.gov/articles/PMC13537245/) * DOI: [ 10.1126/sciadv.aeg8202 ](https://doi.org/10.1126/sciadv.aeg8202) Item in Clipboard Full text links Cite Display options Display options Format Abstract PubMed PMID ## Abstract 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
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