Alterations of gut microbiome accelerate multiple myeloma progression by increasing the relative abundances of nitrogen-recycling bacteria

From BugSigDB
Reviewed Marked as Reviewed by Claregrieve1 on 2022/07/1
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
Authors
Jian X, Zhu Y, Ouyang J, Wang Y, Lei Q, Xia J, Guan Y, Zhang J, Guo J, He Y, Wang J, Li J, Lin J, Su M, Li G, Wu M, Qiu L, Xiang J, Xie L, Jia W, Zhou W
Journal
Microbiome
Year
2020
Keywords:
Fecal microbiota transplantation, Gut microbiome, Multiple myeloma, Nitrogen-recycling bacteria
BACKGROUND: Gut microbiome alterations are closely related to human health and linked to a variety of diseases. Although great efforts have been made to understand the risk factors for multiple myeloma (MM), little is known about the role of the gut microbiome and alterations of its metabolic functions in the development of MM. RESULTS: Here, in a cohort of newly diagnosed patients with MM and healthy controls (HCs), significant differences in metagenomic composition were discovered, for the first time, with higher bacterial diversity in MM. Specifically, nitrogen-recycling bacteria such as Klebsiella and Streptococcus were significantly enriched in MM. Also, the bacteria enriched in MM were significantly correlated with the host metabolome, suggesting strong metabolic interactions between microbes and the host. In addition, the MM-enriched bacteria likely result from the regulation of urea nitrogen accumulated during MM progression. Furthermore, by performing fecal microbiota transplantation (FMT) into 5TGM1 mice, we proposed a mechanistic explanation for the interaction between MM-enriched bacteria and MM progression via recycling urea nitrogen. Further experiments validated that Klebsiella pneumoniae promoted MM progression via de novo synthesis of glutamine in mice and that the mice fed with glutamine-deficient diet exhibited slower MM progression. CONCLUSIONS: Overall, our findings unveil a novel function of the altered gut microbiome in accelerating the malignant progression of MM and open new avenues for novel treatment strategies via manipulation of the intestinal microbiota of MM patients. Video abstract.

Experiment 1


Reviewed Marked as Reviewed by Claregrieve1 on 2022/07/1

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): Claregrieve1, WikiWorks, Victoria

Subjects

Location of subjects
China
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
Multiple myeloma Al amyloidosis,amyloidosis, systemic,Kahler disease,Kahler's disease,medullary plasmacytoma,multiple myeloma,multiple myeloma/plasma cell myeloma,myeloid neoplasm of plasma cell,myeloma,myeloma - multiple,myeloma, multiple,myeloma, plasma cell, malignant,myelomatosis,plasma cell myeloid neoplasm,plasma cell myeloma,Multiple myeloma
Group 0 name Corresponds to the control (unexposed) group for case-control studies
healthy control
Group 1 name Corresponds to the case (exposed) group for case-control studies
multiple myeloma patients
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
newly diagnosed multiple myeloma patients
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
19

Lab analysis

Sequencing type
16S
16S variable region One or more hypervariable region(s) of the bacterial 16S gene
V1-V2
Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
RT-qPCR

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
raw counts
Statistical test
DESeq2
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
Matched on Factors on which subjects have been matched on in a case-control study
age, sex

Alpha Diversity

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

Signature 1

Reviewed Marked as Reviewed by Claregrieve1 on 2022/07/1

Curated date: 2021/01/10

Curator: William Lam

Revision editor(s): WikiWorks

Source: Supplemental table S2

Description: The differential species and subspecies identified by DESeq2 (abs(log2(fold change)) > 1 and adjusted P < 0.05) enriched in multiple myeloma patients and healthy controls

Abundance in Group 1: increased abundance in multiple myeloma patients

NCBI Quality ControlLinks
Klebsiella pneumoniae
Klebsiella variicola
Streptococcus oralis
Streptococcus gordonii
Enterobacter cloacae
Streptococcus thermophilus
Streptococcus parasanguinis
Streptococcus salivarius
Bifidobacterium dentium
Citrobacter freundii
Collinsella aerofaciens
Streptococcus mitis
Klebsiella aerogenes
Xylanibacter ruminicola
Prevotella fusca
Streptococcus anginosus
Prevotella melaninogenica
Intestinimonas butyriciproducens
Streptococcus pneumoniae
Raoultella ornithinolytica
Bifidobacterium adolescentis
Aggregatibacter aphrophilus
Enterobacter asburiae
Megasphaera elsdenii
Oscillibacter valericigenes

Revision editor(s): WikiWorks

Signature 2

Reviewed Marked as Reviewed by Claregrieve1 on 2022/07/1

Curated date: 2021/01/10

Curator: William Lam

Revision editor(s): WikiWorks

Source: Supplemental table S2

Description: The differential species and subspecies identified by DESeq2 (abs(log2(Fold Change)) > 1 and adjusted P < 0.05) enriched in multiple myeloma patients and healthy controls

Abundance in Group 1: decreased abundance in multiple myeloma patients

NCBI Quality ControlLinks
Streptococcus pasteurianus
Lachnoclostridium phytofermentans
Clostridium baratii
Clostridium saccharobutylicum
Butyrivibrio proteoclasticus
Clostridioides difficile
Butyrivibrio hungatei
Bacteroides cellulosilyticus
Clostridium saccharoperbutylacetonicum
Parabacteroides sp.
Bacteroides ovatus
Herbinix luporum
Bacteroides thetaiotaomicron
Parabacteroides distasonis
Lachnospira eligens
Bacteroides caccae
Bifidobacterium catenulatum
Clostridium beijerinckii
Paraclostridium sordellii
Clostridium botulinum
Anaerostipes hadrus
Megamonas hypermegale
Clostridium butyricum
Bifidobacterium catenulatum subsp. kashiwanohense
Bifidobacterium pseudocatenulatum
Fusobacterium varium

Revision editor(s): WikiWorks

Experiment 2


Reviewed Marked as Reviewed by Claregrieve1 on 2022/07/1

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): Claregrieve1, WikiWorks, Victoria

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
healthy controls

Lab analysis

Sequencing type
WMS
16S variable region One or more hypervariable region(s) of the bacterial 16S gene
Not specified
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)
0.01

Alpha Diversity

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

Signature 1

Reviewed Marked as Reviewed by Claregrieve1 on 2022/07/1

Curated date: 2021/01/10

Curator: William Lam

Revision editor(s): Claregrieve1, WikiWorks

Source: Figure 2b, text

Description: Nitrogen- recycling bacteria species with differential abundance in multiple myeloma patients and healthy controls

Abundance in Group 1: increased abundance in multiple myeloma patients

NCBI Quality ControlLinks
Citrobacter freundii
Enterobacter cloacae
Klebsiella aerogenes
Klebsiella pneumoniae
Klebsiella variicola
Raoultella ornithinolytica
Streptococcus gordonii
Streptococcus oralis
Streptococcus pneumoniae
Streptococcus salivarius
Streptococcus mitis

Revision editor(s): Claregrieve1, WikiWorks

Signature 2

Reviewed Marked as Reviewed by Claregrieve1 on 2022/07/1

Curated date: 2021/01/10

Curator: William Lam

Revision editor(s): Claregrieve1, WikiWorks

Source: Figure 2b, text

Description: Nitrogen- recycling bacteria species with differential abundance in multiple myeloma patients and healthy controls

Abundance in Group 1: decreased abundance in multiple myeloma patients

NCBI Quality ControlLinks
Anaerostipes hadrus
Lacrimispora saccharolytica
Clostridium butyricum

Revision editor(s): Claregrieve1, WikiWorks