Gut microbiome diversity is an independent predictor of survival in cervical cancer patients receiving chemoradiation

Study information

Reviewed Marked as Reviewed by Chloe on 2023-3-20

study design

prospective cohort

Citation

PMID PubMed identifier for scientific articles.

33619320

DOI Digital object identifier for electronic documents.

10.1038/s42003-021-01741-x

URI

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7900251/pdf/42003_2021_Article_1741.pdf

Authors

Sims TT, El Alam MB, Karpinets TV, Dorta-Estremera S, Hegde VL, Nookala S, Yoshida-Court K, Wu X, Biegert GWG, Delgado Medrano AY, Solley T, Ahmed-Kaddar M, Chapman BV, Sastry KJ, Mezzari MP, Petrosino JF, Lin LL, Ramondetta L, Jhingran A, Schmeler KM, Ajami NJ, Wargo J, Colbert LE, Klopp AH

Journal

Communications biology

Year

2021

Diversity of the gut microbiome is associated with higher response rates for cancer patients receiving immunotherapy but has not been investigated in patients receiving radiation therapy. Additionally, current studies investigating the gut microbiome and outcomes in cancer patients may not have adjusted for established risk factors. Here, we sought to determine if diversity and composition of the gut microbiome was independently associated with survival in cervical cancer patients receiving chemoradiation. Our study demonstrates that the diversity of gut microbiota is associated with a favorable response to chemoradiation. Additionally, compositional variation among patients correlated with short term and long-term survival. Short term survivor fecal samples were significantly enriched in Porphyromonas, Porphyromonadaceae, and Dialister, whereas long term survivor samples were significantly enriched in Escherichia Shigella, Enterobacteriaceae, and Enterobacteriales. Moreover, analysis of immune cells from cervical tumor brush samples by flow cytometry revealed that patients with a high microbiome diversity had increased tumor infiltration of CD4+ lymphocytes as well as activated subsets of CD4 cells expressing ki67+ and CD69+ over the course of radiation therapy. Modulation of the gut microbiota before chemoradiation might provide an alternative way to enhance treatment efficacy and improve treatment outcomes in cervical cancer patients.

Experiment 1

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Reviewed Marked as Reviewed by Chloe on 2023-3-20

Curated date: 2023/03/14

Curator: BLESSING123

Revision editor(s): BLESSING123, Chloe

Subjects

Location of subjects: United States of America

Host species Species from which microbiome was sampled. Contact us to have more species added.: 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,feces

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology: Survival time survival,time of survival,Survival time,survival time

Group 0 name Corresponds to the control (unexposed) group for case-control studies: Long-term survivors

Group 1 name Corresponds to the case (exposed) group for case-control studies: Short-term surviviors

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: Cervical Cancer patients that had a follow-up of one year or less because of death

Group 0 sample size Number of subjects in the control (unexposed) group: 48

Group 1 sample size Number of subjects in the case (exposed) group: 7

Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any): None

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

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).: relative abundances

Statistical test: LEfSe

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

MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?: No

LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool: 3.5

Signature 1

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Reviewed Marked as Reviewed by Chloe on 2023-3-20

Curated date: 2023/03/16

Curator: BLESSING123

Revision editor(s): BLESSING123, Chloe

Source: Figure 2a

Description: The different abundance of bacterial taxa between the two groups were identified by LEfSe. It was significantly different when alpha value of the factorial Kruskal–Wallis test was <0.05 and the logarithmic LDA score was >3.5. The left histogram showed the LDA scores of taxa differentially abundant between the two groups. The taxonomy was listed, followed by its core group. Putative species (Specific OTUs) identified as significantly more enriched/depleted (Fisher/Wilcoxon test p value < 0.05) in patients with short-term vs longterm in baseline samples

Abundance in Group 1: increased abundance in Short-term surviviors

NCBI	Quality Control	Links
Bacilli
Campylobacter
Campylobacteraceae
Campylobacterales
Campylobacterota
Enterobacterales
Enterobacteriaceae
Escherichia/Shigella sp.
Haemophilus
Lactobacillaceae
Lactobacillus
Pasteurellaceae
Pasteurellales
Tyzzerella
Veillonella

Revision editor(s): BLESSING123, Chloe

Signature 2

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Reviewed Marked as Reviewed by Chloe on 2023-3-20

Curated date: 2023/03/16

Curator: BLESSING123

Revision editor(s): BLESSING123, Chloe

Source: Figure 2a

Description: The different abundance of bacterial taxa between the two groups were identified by LEfSe. It was significantly different when alpha value of the factorial Kruskal–Wallis test was <0.05 and the logarithmic LDA score was >3.5. The left histogram showed the LDA scores of taxa differentially abundant between the two groups. The taxonomy was listed, followed by its core group. Putative species (Specific OTUs) identified as significantly more enriched/depleted (Fisher/Wilcoxon test p value < 0.05) in patients with short-term vs longterm in baseline samples

Abundance in Group 1: decreased abundance in Short-term surviviors

NCBI	Quality Control	Links
Dialister
Porphyromonadaceae
Porphyromonas

Revision editor(s): BLESSING123, Chloe