Chemotherapy-driven dysbiosis in the intestinal microbiome

Study information

Reviewed Marked as Reviewed by Claregrieve1 on 2022/09/29

study design

prospective cohort

Citation

PMID PubMed identifier for scientific articles.

26147207

DOI Digital object identifier for electronic documents.

10.1111/apt.13302

URI

Authors

Montassier E, Gastinne T, Vangay P, Al-Ghalith GA, Bruley des Varannes S, Massart S, Moreau P, Potel G, de La Cochetière MF, Batard E, Knights D

Journal

Alimentary pharmacology & therapeutics

Year

2015

BACKGROUND: Chemotherapy is commonly used as myeloablative conditioning treatment to prepare patients for haematopoietic stem cell transplantation (HSCT). Chemotherapy leads to several side effects, with gastrointestinal (GI) mucositis being one of the most frequent. Current models of GI mucositis pathophysiology are generally silent on the role of the intestinal microbiome. AIM: To identify functional mechanisms by which the intestinal microbiome may play a key role in the pathophysiology of GI mucositis, we applied high-throughput DNA-sequencing analysis to identify microbes and microbial functions that are modulated following chemotherapy. METHODS: We amplified and sequenced 16S rRNA genes from faecal samples before and after chemotherapy in 28 patients with non-Hodgkin's lymphoma who received the same myeloablative conditioning regimen and no other concomitant therapy such as antibiotics. RESULTS: We found that faecal samples collected after chemotherapy exhibited significant decreases in abundances of Firmicutes (P = 0.0002) and Actinobacteria (P = 0.002) and significant increases in abundances of Proteobacteria (P = 0.0002) compared to samples collected before chemotherapy. Following chemotherapy, patients had reduced capacity for nucleotide metabolism (P = 0.0001), energy metabolism (P = 0.001), metabolism of cofactors and vitamins (P = 0.006), and increased capacity for glycan metabolism (P = 0.0002), signal transduction (P = 0.0002) and xenobiotics biodegradation (P = 0.002). CONCLUSIONS: Our study identifies a severe compositional and functional imbalance in the gut microbial community associated with chemotherapy-induced GI mucositis. The functional pathways implicated in our analysis suggest potential directions for the development of intestinal microbiome-targeted interventions in cancer patients.

Experiment 1

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Curated date: 2021/01/10

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Subjects

Location of subjects: France

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

Group 0 name Corresponds to the control (unexposed) group for case-control studies: pre-chemotherapy

Group 1 name Corresponds to the case (exposed) group for case-control studies: post-chemotherapy

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: non-Hodgkin's lymphoma patients post myeloablative conditiong regimen (chemotherapy) fecal sampling for 5 consecutive days of high-dose Carmustine, Etoposide, Aracytine and Melphalan and with no antibiotics treatment after starting regimen

Group 0 sample size Number of subjects in the control (unexposed) group: 28

Group 1 sample size Number of subjects in the case (exposed) group: 15

Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any): 1 month

Lab analysis

Sequencing type: 16S

16S variable region One or more hypervariable region(s) of the bacterial 16S gene: V5-V6

Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance: Roche454

Statistical Analysis

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

Statistical test: Mann-Whitney (Wilcoxon)

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)?: Yes

Alpha Diversity

Richness Number of species: decreased

Signature 1

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Reviewed Marked as Reviewed by Claregrieve1 on 2022/09/29

Curated date: 2021/01/10

Curator: William Lam

Revision editor(s): Claregrieve1, WikiWorks

Source: Supplemental Table S1a-c, text

Description: Differential microbial taxa abundance for non-Hodgkins Lymphoma patients from the fecal samples collected before and after chemotherapy

Abundance in Group 1: increased abundance in post-chemotherapy

NCBI	Quality Control	Links
Aerococcaceae
Carnobacteriaceae
Citrobacter
Enterobacteriaceae
Enterococcaceae
Enterococcus
Parabacteroides
Porphyromonadaceae
Pseudomonadota
Atopobium
Klebsiella

Revision editor(s): Claregrieve1, WikiWorks

Signature 2

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Reviewed Marked as Reviewed by Claregrieve1 on 2022/09/29

Curated date: 2021/01/10

Curator: William Lam

Revision editor(s): Claregrieve1, WikiWorks

Source: Supplemental Table S1a-c, text

Description: Differential microbial taxa abundance for non-Hodgkins Lymphoma patients from the fecal samples collected before and after chemotherapy

Abundance in Group 1: decreased abundance in post-chemotherapy

NCBI	Quality Control	Links
Actinomycetota
Adlercreutzia
Anaerococcus
Atopobium
Bifidobacteriaceae
Bifidobacterium
Blautia
Clostridium
Collinsella
Coprococcus
Coriobacteriaceae
Dorea
Enterobacteriaceae
Bacillota
Klebsiella
Lachnospira
Lachnospiraceae
Oscillospira
Oscillospiraceae
Roseburia
Ruminococcus
Clostridiales bacterium

Revision editor(s): Claregrieve1, WikiWorks