Minimal residual disease negativity in multiple myeloma is associated with intestinal microbiota composition

From BugSigDB
Needs review
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI Uniform resource identifier for web resources.
Authors
Pianko MJ, Devlin SM, Littmann ER, Chansakul A, Mastey D, Salcedo M, Fontana E, Ling L, Tavitian E, Slingerland JB, Slingerland AE, Clurman A, Gomes ALC, Taur Y, Pamer EG, Peled JU, van den Brink MRM, Landgren O, Lesokhin AM
Journal
Blood advances
Year
2019
Patients with multiple myeloma (MM) who achieve minimal residual disease (MRD) negativity after upfront treatment have superior outcomes compared with those who remain MRD+ Recently, associations have been shown between specific commensal microbes and development of plasma cell disorders. Here, we report the association between intestinal microbiota composition and treatment outcome in MM. Microbiota composition of fecal samples collected from 34 MM patients after induction therapy and at the time of flow cytometry-based bone marrow MRD testing was determined by 16S ribosomal RNA sequencing. We observed a higher relative abundance of Eubacterium hallii in the 16 MRD- patients relative to the 18 MRD+ patients. No association was observed between microbial relative abundance and autologous stem cell transplantation history or MM paraprotein isotype. No differences in microbiota α diversity were observed between MRD- and MRD+ patients. The potential association of microbiota composition with treatment response in MM patients is an important parameter for additional correlative and clinical investigation.

Experiment 1


Needs review

Curated date: 2021/01/10

Curator: WikiWorks743

Revision editor(s): WikiWorks753, WikiWorks743

Subjects

Location of subjects
United States of America
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
acute lymphoblastic leukemia acute lymphoblastic leukemia,acute lymphoblastic leukemia (ALL),acute lymphoblastic leukemia (disease),acute lymphoblastic leukemia/lymphoma,acute lymphocytic leukaemia,acute lymphocytic leukemia,acute lymphocytic leukemias,acute lymphogenous leukemia,acute lymphoid leukemia,ALL,ALL - acute lymphocytic leukemia,leukemia, lymphoblastic, malignant,lymphoblastic leukemia,lymphoblastic leukemia, acute,precursor cell lymphoblastic leukemia,precursor Lymphoblasic leukemia,precursor lymphoblastic leukemia
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Minimal Residual Disease- (positivity) with Allogenic Stem Cell Transplant
Group 1 name Corresponds to the case (exposed) group for case-control studies
Minimal Residual Disease- (negativity) with Allogenic Stem Cell Transplant
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Patients with multiple myeloma (MM) who achieve minimal residual disease (MRD) negativity (MRD-) after upfront treatment
Group 0 sample size Number of subjects in the control (unexposed) group
18
Group 1 sample size Number of subjects in the case (exposed) group
16

Lab analysis

Sequencing type
16S
16S variable region One or more hypervariable region(s) of the bacterial 16S gene
V4-V5
Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
Illumina

Statistical Analysis

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)?
Yes
LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
2


Alpha Diversity

Inverse Simpson Modification of Simpsons index D as 1/D to obtain high values in datasets of high diversity and vice versa
unchanged

Signature 1

Needs review

Curated date: 2020-05-16

Curator: William Lam

Revision editor(s): WikiWorks743

Source: Figure 1a

Description: Linear discriminant analysis (LDA) effect size analysis of microbiota differentially associated with MRD status with subclass of autologous stem cell transplantation (ASCT)

Abundance in Group 1: increased abundance in Minimal Residual Disease- (negativity) with Allogenic Stem Cell Transplant

NCBI Links
Faecalibacterium prausnitzii
Faecalibacterium
Anaerobutyricum hallii
Ethanoligenens harbinense
Ethanoligenens
Sporobacter termitidis
Sporobacter

Revision editor(s): WikiWorks743

Signature 2

Needs review

Curated date: 2020-05-16

Curator: William Lam

Revision editor(s): WikiWorks743

Source: Figure 1a

Description: Linear discriminant analysis (LDA) effect size analysis of microbiota differentially associated with MRD status with subclass of autologous stem cell transplantation (ASCT)

Abundance in Group 1: decreased abundance in Minimal Residual Disease- (negativity) with Allogenic Stem Cell Transplant

NCBI Links
Actinomyces israelii
Actinomyces naeslundii
Micrococcales
Micrococcaceae
Rothia
Rothia dentocariosa
Rothia mucilaginosa
[Clostridium] nexile
Streptococcus equinus

Revision editor(s): WikiWorks743

Experiment 2


Needs review

Curated date: 2021/01/10

Curator: WikiWorks743

Revision editor(s): WikiWorks753, WikiWorks743

Subjects

Location of subjects
United States of America
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
acute lymphoblastic leukemia acute lymphoblastic leukemia,acute lymphoblastic leukemia (ALL),acute lymphoblastic leukemia (disease),acute lymphoblastic leukemia/lymphoma,acute lymphocytic leukaemia,acute lymphocytic leukemia,acute lymphocytic leukemias,acute lymphogenous leukemia,acute lymphoid leukemia,ALL,ALL - acute lymphocytic leukemia,leukemia, lymphoblastic, malignant,lymphoblastic leukemia,lymphoblastic leukemia, acute,precursor cell lymphoblastic leukemia,precursor Lymphoblasic leukemia,precursor lymphoblastic leukemia
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Minimal Residual Disease- (positivity) with Allogenic Stem Cell Transplant
Group 1 name Corresponds to the case (exposed) group for case-control studies
Minimal Residual Disease- (negativity) with Allogenic Stem Cell Transplant
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Patients with multiple myeloma (MM) who achieve minimal residual disease (MRD) negativity (MRD-) after upfront treatment
Group 0 sample size Number of subjects in the control (unexposed) group
18
Group 1 sample size Number of subjects in the case (exposed) group
16

Lab analysis

Sequencing type
16S
Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
Illumina

Statistical Analysis

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)?
Yes
LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
2


Alpha Diversity

Richness Number of species
increased

Signature 1

Needs review

Curated date: 2020-05-16

Curator: William Lam

Revision editor(s): WikiWorks743

Source: Figure 1b

Description: Relative abundance of genera Eubacterium and Faecalibacterium by MRD status

Abundance in Group 1: increased abundance in Minimal Residual Disease- (negativity) with Allogenic Stem Cell Transplant

NCBI Links
Eubacterium

Revision editor(s): WikiWorks743

Signature 2

Needs review

Curated date: 2020-05-16

Curator: William Lam

Revision editor(s): WikiWorks743

Source: Figure 1b

Description: Relative abundance of genera Eubacterium and Faecalibacterium by MRD status

Abundance in Group 1: increased abundance in Minimal Residual Disease- (negativity) with Allogenic Stem Cell Transplant

NCBI Links
Faecalibacterium

Revision editor(s): WikiWorks743

Experiment 3


Needs review

Curated date: 2021/01/10

Curator: WikiWorks743

Revision editor(s): WikiWorks753, WikiWorks743

Subjects

Location of subjects
United States of America
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
acute lymphoblastic leukemia acute lymphoblastic leukemia,acute lymphoblastic leukemia (ALL),acute lymphoblastic leukemia (disease),acute lymphoblastic leukemia/lymphoma,acute lymphocytic leukaemia,acute lymphocytic leukemia,acute lymphocytic leukemias,acute lymphogenous leukemia,acute lymphoid leukemia,ALL,ALL - acute lymphocytic leukemia,leukemia, lymphoblastic, malignant,lymphoblastic leukemia,lymphoblastic leukemia, acute,precursor cell lymphoblastic leukemia,precursor Lymphoblasic leukemia,precursor lymphoblastic leukemia
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Minimal Residual Disease- (positivity) with Allogenic Stem Cell Transplant
Group 1 name Corresponds to the case (exposed) group for case-control studies
Minimal Residual Disease- (negativity) with Allogenic Stem Cell Transplant
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Patients with multiple myeloma (MM) who achieve minimal residual disease (MRD) negativity (MRD-) after upfront treatment
Group 0 sample size Number of subjects in the control (unexposed) group
18
Group 1 sample size Number of subjects in the case (exposed) group
16

Lab analysis

Sequencing type
16S
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
MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
Yes
LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
2


Alpha Diversity

Richness Number of species
increased

Signature 1

Needs review

Curated date: 2020-05-16

Curator: William Lam

Revision editor(s): WikiWorks743

Source: Figure 1c

Description: Forest plots showing effect of covariates on relative abundance of E hallii and F prausnitzii

Abundance in Group 1: increased abundance in Minimal Residual Disease- (negativity) with Allogenic Stem Cell Transplant

NCBI Links
Faecalibacterium prausnitzii

Revision editor(s): WikiWorks743

Experiment 4


Needs review

Curated date: 2021/01/10

Curator: WikiWorks743

Revision editor(s): WikiWorks753, WikiWorks743

Subjects

Location of subjects
United States of America
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
acute lymphoblastic leukemia acute lymphoblastic leukemia,acute lymphoblastic leukemia (ALL),acute lymphoblastic leukemia (disease),acute lymphoblastic leukemia/lymphoma,acute lymphocytic leukaemia,acute lymphocytic leukemia,acute lymphocytic leukemias,acute lymphogenous leukemia,acute lymphoid leukemia,ALL,ALL - acute lymphocytic leukemia,leukemia, lymphoblastic, malignant,lymphoblastic leukemia,lymphoblastic leukemia, acute,precursor cell lymphoblastic leukemia,precursor Lymphoblasic leukemia,precursor lymphoblastic leukemia
Group 0 name Corresponds to the control (unexposed) group for case-control studies
female
Group 1 name Corresponds to the case (exposed) group for case-control studies
males
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Patients with multiple myeloma (MM) who achieve minimal residual disease (MRD) negativity (MRD-) after upfront treatment
Group 0 sample size Number of subjects in the control (unexposed) group
18
Group 1 sample size Number of subjects in the case (exposed) group
16

Lab analysis

Sequencing type
16S
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
MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
Yes
LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
2


Alpha Diversity

Richness Number of species
increased

Signature 1

Needs review

Curated date: 2020-05-16

Curator: William Lam

Revision editor(s): WikiWorks743

Source: Figure 1c

Description: Forest plots showing effect of covariates on relative abundance of E hallii and F prausnitzii

Abundance in Group 1: increased abundance in males

NCBI Links
Faecalibacterium prausnitzii

Revision editor(s): WikiWorks743

Experiment 5


Needs review

Curated date: 2021/01/10

Curator: WikiWorks743

Revision editor(s): WikiWorks753, WikiWorks743

Subjects

Location of subjects
United States of America
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
acute lymphoblastic leukemia acute lymphoblastic leukemia,acute lymphoblastic leukemia (ALL),acute lymphoblastic leukemia (disease),acute lymphoblastic leukemia/lymphoma,acute lymphocytic leukaemia,acute lymphocytic leukemia,acute lymphocytic leukemias,acute lymphogenous leukemia,acute lymphoid leukemia,ALL,ALL - acute lymphocytic leukemia,leukemia, lymphoblastic, malignant,lymphoblastic leukemia,lymphoblastic leukemia, acute,precursor cell lymphoblastic leukemia,precursor Lymphoblasic leukemia,precursor lymphoblastic leukemia
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Minimal Residual Disease- (positivity) with Allogenic Stem Cell Transplant
Group 1 name Corresponds to the case (exposed) group for case-control studies
Minimal Residual Disease- (negativity) with Allogenic Stem Cell Transplant
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Patients with multiple myeloma (MM) who achieve minimal residual disease (MRD) negativity (MRD-) after upfront treatment
Group 0 sample size Number of subjects in the control (unexposed) group
18
Group 1 sample size Number of subjects in the case (exposed) group
16

Lab analysis

Sequencing type
16S
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
MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
Yes
LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
2


Alpha Diversity

Richness Number of species
increased

Signature 1

Needs review

Curated date: 2020-05-16

Curator: William Lam

Revision editor(s): WikiWorks743

Source: Figure 1c

Description: Forest plots showing effect of covariates on relative abundance of E hallii and F prausnitzii

Abundance in Group 1: increased abundance in Minimal Residual Disease- (negativity) with Allogenic Stem Cell Transplant

NCBI Links
Anaerobutyricum hallii

Revision editor(s): WikiWorks743

Experiment 6


Needs review

Curated date: 2021/01/10

Curator: WikiWorks743

Revision editor(s): WikiWorks753, WikiWorks743

Subjects

Location of subjects
United States of America
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
acute lymphoblastic leukemia acute lymphoblastic leukemia,acute lymphoblastic leukemia (ALL),acute lymphoblastic leukemia (disease),acute lymphoblastic leukemia/lymphoma,acute lymphocytic leukaemia,acute lymphocytic leukemia,acute lymphocytic leukemias,acute lymphogenous leukemia,acute lymphoid leukemia,ALL,ALL - acute lymphocytic leukemia,leukemia, lymphoblastic, malignant,lymphoblastic leukemia,lymphoblastic leukemia, acute,precursor cell lymphoblastic leukemia,precursor Lymphoblasic leukemia,precursor lymphoblastic leukemia
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Age greater than 65 years old
Group 1 name Corresponds to the case (exposed) group for case-control studies
Age less than 65 years old
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Patients with multiple myeloma (MM) who achieve minimal residual disease (MRD) negativity (MRD-) after upfront treatment
Group 0 sample size Number of subjects in the control (unexposed) group
18
Group 1 sample size Number of subjects in the case (exposed) group
16

Lab analysis

Sequencing type
16S
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
MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
Yes
LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
2


Alpha Diversity

Richness Number of species
increased

Signature 1

Needs review

Curated date: 2020-05-16

Curator: William Lam

Revision editor(s): WikiWorks743

Source: Figure 1c

Description: Forest plots showing effect of covariates on relative abundance of E hallii and F prausnitzii

Abundance in Group 1: increased abundance in Age less than 65 years old

NCBI Links
Anaerobutyricum hallii

Revision editor(s): WikiWorks743