Gut Microbiota Profiling in Patients With HER2-Negative Metastatic Breast Cancer Receiving Metronomic Chemotherapy of Capecitabine Compared to Those Under Conventional Dosage

Study information

Reviewed Marked as Reviewed by Fatima on 2022/09/7

study design

prospective cohort

Citation

PMID PubMed identifier for scientific articles.

32733788

DOI Digital object identifier for electronic documents.

10.3389/fonc.2020.00902

URI

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7358584/

Authors

Guan X, Ma F, Sun X, Li C, Li L, Liang F, Li S, Yi Z, Liu B, Xu B

Journal

Frontiers in oncology

Year

2020

Keywords:

breast cancer, capecitabine, gut microbiota, maintenance chemotherapy, metronomic chemotherapy

Purpose: Low-dose metronomic chemotherapy can achieve disease control with reduced toxicity compared to conventional chemotherapy in maximum tolerated dose. Characterizing the gut microbiota of cancer patients under different dosage regimens may describe a new role of gut microbiota associated with drug efficacy. Therefore, we evaluated the composition and the function of gut microbiome associated with metronomic capecitabine compared to conventional dosage. Methods: The fecal samples of HER2-negative metastatic breast cancer patients treated with capecitabine as maintenance chemotherapy were collected and analyzed by 16S ribosome RNA gene sequencing. Results: A total of 15 patients treated with metronomic capecitabine were compared to 16 patients under a conventional dose. The unweighted-unifrac index of the metronomic group was statistically significantly lower than that of the routine group (P = 0.025). Besides that, the Bray-Curtis distance-based redundancy analysis illustrated that the microbial genera between the two groups can be separated partly. Nine Kyoto Encyclopedia of Genes and Genomes (KEGG) modules were enriched in the metronomic group, while no KEGG modules were significantly enriched in the routine group. Moreover, univariate and multivariate analyses suggested that the median progression-free survival (PFS) was significantly shorter in patients with the gut microbial composition of Slackia (9.2 vs. 32.7 months, P = 0.004), while the patients with Blautia obeum had a significantly prolonged PFS than those without (32.7 vs. 12.9 months, P = 0.013). Conclusions: The proof-of-principle study suggested that the gut microbiota of patients receiving metronomic chemotherapy was different in terms of diversity, composition, and function from those under conventional chemotherapy, and the presence of specific bacterial species may act as microbial markers associated with drug resistance monitoring and prognostic evaluation.

Experiment 1

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Reviewed Marked as Reviewed by Fatima on 2022/09/7

Curated date: 2022/08/29

Curator: Sharmilac

Revision editor(s): Sharmilac, Fatima, WikiWorks

Subjects

Location of subjects: China

Host species Species from which microbiome was sampled (if applicable): Homo sapiens

Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology: Feces Cow dung,Cow pat,Droppings,Dung,Excrement,Excreta,Faeces,Fecal material,Fecal matter,Fewmet,Frass,Guano,Matières fécales@fr,Merde@fr,Ordure,Partie de la merde@fr,Piece of shit,Porción de mierda@es,Portion of dung,Portion of excrement,Portion of faeces,Portion of fecal material,Portion of fecal matter,Portion of feces,Portion of guano,Portion of scat,Portionem cacas,Scat,Spoor,Spraint,Stool,Teil der fäkalien@de,Feces

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology: response to immunochemotherapy response to immunochemotherapy

Group 0 name Corresponds to the control (unexposed) group for case-control studies: non-responders (patients treated with conventional dose)
Group 1 name Corresponds to the case (exposed) group for case-control studies: responders (patients treated with metronomic dose of capecitabine)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: Patients with HER2-negative metastatic breast cancer who receive metronomic capecitabine as maintenance treatment.
Group 0 sample size Number of subjects in the control (unexposed) group: 16
Group 1 sample size Number of subjects in the case (exposed) group: 15

Lab analysis

Sequencing type: 16S

16S variable region One or more hypervariable region(s) of the bacterial 16S gene: V4

Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance: Illumina

Statistical Analysis

Statistical test: Mann-Whitney (Wilcoxon)

Significance threshold p-value or FDR threshold used for differential abundance testing (if any): 0.05

Alpha Diversity

Pielou Quantifies how equal the community is numerically: unchanged
Shannon Estimator of species richness and species evenness: more weight on species richness: unchanged

Signature 1

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Reviewed Marked as Reviewed by Fatima on 2022/09/7

Curated date: 2022/08/29

Curator: Sharmilac

Revision editor(s): Sharmilac, Merit

Source: Table 2, Figure 2B, text

Description: Comparison of the distribution of gut microbiota between the metronomic group and the routine group at different levels. (B) Distribution of the gut microbiota composition in the metronomic group and the routine group at the genus level.

Abundance in Group 1: increased abundance in responders (patients treated with metronomic dose of capecitabine)

NCBI	Quality Control	Links
Megamonas
Veillonellaceae
Veillonella
Veillonella sp.
Veillonellales
Megamonas sp.
unclassified Megamonas
unclassified Veillonella
unclassified Veillonellaceae