Chemotherapy-driven dysbiosis in the intestinal microbiome

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Reviewed Marked as Reviewed by Claregrieve1 on 2022/09/29
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
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


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

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): Claregrieve1, WikiWorks, Victoria

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
Non-Hodgkins lymphoma NHL,non-Hodgkin lymphoma,non-Hodgkin's lymphoma,non-Hodgkin's lymphoma (NHL),non-Hodgkins lymphoma,Non-Hodgkins lymphoma
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

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 ControlLinks
Aerococcaceae
Carnobacteriaceae
Citrobacter
Enterobacteriaceae
Enterococcaceae
Enterococcus
Parabacteroides
Porphyromonadaceae
Pseudomonadota
Atopobium
Klebsiella

Revision editor(s): Claregrieve1, WikiWorks

Signature 2

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 ControlLinks
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