Characterization of oral and gut microbiome temporal variability in hospitalized cancer patients

Study information

Reviewed Marked as Reviewed by Claregrieve1 on 2022/11/5

study design

time series / longitudinal observational

Citation

PMID PubMed identifier for scientific articles.

28245856

DOI Digital object identifier for electronic documents.

10.1186/s13073-017-0409-1

URI

Authors

Galloway-Peña JR, Smith DP, Sahasrabhojane P, Wadsworth WD, Fellman BM, Ajami NJ, Shpall EJ, Daver N, Guindani M, Petrosino JF, Kontoyiannis DP, Shelburne SA

Journal

Genome medicine

Year

2017

Keywords:

Antibiotics, Chemotherapy, Leukemia, Microbiome, Temporal variability

BACKGROUND: Understanding longitudinal variability of the microbiome in ill patients is critical to moving microbiome-based measurements and therapeutics into clinical practice. However, the vast majority of data regarding microbiome stability are derived from healthy subjects. Herein, we sought to determine intra-patient temporal microbiota variability, the factors driving such variability, and its clinical impact in an extensive longitudinal cohort of hospitalized cancer patients during chemotherapy. METHODS: The stool (n = 365) and oral (n = 483) samples of 59 patients with acute myeloid leukemia (AML) undergoing induction chemotherapy (IC) were sampled from initiation of chemotherapy until neutrophil recovery. Microbiome characterization was performed via analysis of 16S rRNA gene sequencing. Temporal variability was determined using coefficients of variation (CV) of the Shannon diversity index (SDI) and unweighted and weighted UniFrac distances per patient, per site. Measurements of intra-patient temporal variability and patient stability categories were analyzed for their correlations with genera abundances. Groups of patients were analyzed to determine if patients with adverse outcomes had significantly different levels of microbiome temporal variability. Potential clinical drivers of microbiome temporal instability were determined using multivariable regression analyses. RESULTS: Our cohort evidenced a high degree of intra-patient temporal instability of stool and oral microbial diversity based on SDI CV. We identified statistically significant differences in the relative abundance of multiple taxa amongst individuals with different levels of microbiota temporal stability. Increased intra-patient temporal variability of the oral SDI was correlated with increased risk of infection during IC (P = 0.02), and higher stool SDI CVs were correlated with increased risk of infection 90 days post-IC (P = 0.04). Total days on antibiotics was significantly associated with increased temporal variability of both oral microbial diversity (P = 0.03) and community structure (P = 0.002). CONCLUSIONS: These data quantify the longitudinal variability of the oral and gut microbiota in AML patients, show that increased variability was correlated with adverse clinical outcomes, and offer the possibility of using stabilizing taxa as a method of focused microbiome repletion. Furthermore, these results support the importance of longitudinal microbiome sampling and analyses, rather than one time measurements, in research and future clinical practice.

Experiment 2

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Reviewed Marked as Reviewed by Claregrieve1 on 2022/11/5

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): Claregrieve1, WikiWorks, Victoria

Differences from previous experiment shown

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: Buccal mucosa Buccal mucosa,buccal mucosa

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology: Acute myeloid leukemia acute granulocytic leukemia,acute myeloblastic leukemia,acute myelocytic leukemia,acute myelogenous leukemia,acute myelogenous leukemias,acute myeloid leukemia,acute myeloid leukemia (AML),acute non lymphoblastic leukemia,acute Nonlymphocytic leukemia,acute nonlymphocytic leukemia,AML,AML - acute myeloid leukemia,ANLL,hematopoeitic - acute Myleogenous leukemia (AML),leukemia, acute myelogenous,leukemia, acute myeloid,leukemia, acute myeloid, susceptibility to,leukemia, myelocytic, acute,myeloid leukemia, acute,Acute myeloid leukemia

Group 0 name Corresponds to the control (unexposed) group for case-control studies: no infection

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

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: acute myeloid leukemia patients that were microbiologically documented with infection during induction chemotherapy before neutrophil recovery

Group 0 sample size Number of subjects in the control (unexposed) group: 30

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

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

Shannon Estimator of species richness and species evenness: more weight on species richness: increased

Signature 1

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Curated date: 2021/01/10

Curator: William Lam

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Source: Figure 5e

Description: Differential microbial abundance between patients who experienced infection and patients who did not

Abundance in Group 1: increased abundance in infection

NCBI	Quality Control	Links
Stenotrophomonas

Revision editor(s): Claregrieve1, WikiWorks

Signature 2

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Reviewed Marked as Reviewed by Claregrieve1 on 2022/11/5

Curated date: 2022/07/28

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Source: Figure 5e

Description: Differential microbial abundance between patients who experienced infection and patients who did not

Abundance in Group 1: decreased abundance in infection

NCBI	Quality Control	Links
Streptococcus

Revision editor(s): Claregrieve1

Experiment 3

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Reviewed Marked as Reviewed by Claregrieve1 on 2022/11/5

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): Claregrieve1, WikiWorks, Victoria

Differences from previous experiment shown

Subjects

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