Dental Biofilm Microbiota Dysbiosis Is Associated With the Risk of Acute Graft-Versus-Host Disease After Allogeneic Hematopoietic Stem Cell Transplantation

Study information

Reviewed Marked as Reviewed by ChiomaBlessing on 2024-3-14

study design

time series / longitudinal observational

Citation

PMID PubMed identifier for scientific articles.

34220852

DOI Digital object identifier for electronic documents.

10.3389/fimmu.2021.692225

URI

Authors

Heidrich V, Bruno JS, Knebel FH, de Molla VC, Miranda-Silva W, Asprino PF, Tucunduva L, Rocha V, Novis Y, Arrais-Rodrigues C, Fregnani ER, Camargo AA

Journal

Frontiers in immunology

Year

2021

Keywords:

acute GVHD, allogeneic HSCT, bone marrow transplant, microbiome dysbiosis, oral microbiota, supragingival plaque

Acute graft-versus-host disease (aGVHD) is one of the major causes of death after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Recently, aGVHD onset was linked to intestinal microbiota (IM) dysbiosis. However, other bacterial-rich gastrointestinal sites, such as the mouth, which hosts several distinctive microbiotas, may also impact the risk of GVHD. The dental biofilm microbiota (DBM) is highly diverse and, like the IM, interacts with host cells and modulates immune homeostasis. We characterized changes in the DBM of patients during allo-HSCT and evaluated whether the DBM could be associated with the risk of aGVHD. DBM dysbiosis during allo-HSCT was marked by a gradual loss of bacterial diversity and changes in DBM genera composition, with commensal genera reductions and potentially pathogenic bacteria overgrowths. High Streptococcus and high Corynebacterium relative abundance at preconditioning were associated with a higher risk of aGVHD (67% vs. 33%; HR = 2.89, P = 0.04 and 73% vs. 37%; HR = 2.74, P = 0.04, respectively), while high Veillonella relative abundance was associated with a lower risk of aGVHD (27% vs. 73%; HR = 0.24, P < 0.01). Enterococcus faecalis bloom during allo-HSCT was observed in 17% of allo-HSCT recipients and was associated with a higher risk of aGVHD (100% vs. 40%; HR = 4.07, P < 0.001) and severe aGVHD (60% vs. 12%; HR = 6.82, P = 0.01). To the best of our knowledge, this is the first study demonstrating that DBM dysbiosis is associated with the aGVHD risk after allo-HSCT.

Experiment 1

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Reviewed Marked as Reviewed by ChiomaBlessing on 2024-3-14

Curated date: 2024/03/06

Curator: Joan Chuks

Revision editor(s): Joan Chuks, Victoria

Subjects

Location of subjects: Brazil

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: Supragingival dental plaque Supragingival plaque,Supragingival dental plaque,supragingival dental plaque

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology: Response to allogeneic hematopoietic stem cell transplant Response to allogeneic hematopoietic stem cell transplant,response to allogeneic hematopoietic stem cell transplant

Group 0 name Corresponds to the control (unexposed) group for case-control studies: Preconditioning (Patients Before Allogeneic Hematopoietic Stem Cell Transplantation)

Group 1 name Corresponds to the case (exposed) group for case-control studies: Engraftment (Patients After Allogeneic Hematopoietic Stem Cell Transplantation)

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: Patients at the final phase of Allogeneic Hematopoietic Stem Cell transplant, when the new transplanted stem cells start to grow and produce new blood cells.

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: 27

Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any): No

Lab analysis

Sequencing type: 16S

16S variable region One or more hypervariable region(s) of the bacterial 16S gene: V3-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).: centered log-ratio

Statistical test: ANCOM

Significance threshold p-value or FDR threshold used for differential abundance testing (if any): 0.7

MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?: No

Alpha Diversity

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

Simpson Estimator of species richness and species evenness: more weight on species evenness: decreased

Richness Number of species: decreased

Signature 1

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Reviewed Marked as Reviewed by ChiomaBlessing on 2024-3-14

Curated date: 2024/03/08

Curator: Joan Chuks

Revision editor(s): Joan Chuks, ChiomaBlessing

Source: Figure 1C

Description: Significant genera relative abundance in the engraftment (After transplantation) group compared to the preconditioning (Before transplantation) group according to ANCOM test (W > 0.7).

Abundance in Group 1: increased abundance in Engraftment (Patients After Allogeneic Hematopoietic Stem Cell Transplantation)

NCBI	Quality Control	Links
Enterococcus
Lactobacillus
Leuconostoc
Mycoplasma
Staphylococcus

Revision editor(s): Joan Chuks, ChiomaBlessing

Signature 2

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Reviewed Marked as Reviewed by ChiomaBlessing on 2024-3-14

Curated date: 2024/03/08

Curator: Joan Chuks

Revision editor(s): Joan Chuks, ChiomaBlessing

Source: Figure 1C

Description: Significant genera relative abundance in the engraftment (After transplantation) group compared to the preconditioning (Before transplantation) group according to ANCOM test (W > 0.7).

Abundance in Group 1: decreased abundance in Engraftment (Patients After Allogeneic Hematopoietic Stem Cell Transplantation)

NCBI	Quality Control	Links
Actinomyces
Gemella
Lachnoanaerobaculum
Leptotrichia
Streptococcus

Revision editor(s): Joan Chuks, ChiomaBlessing

Experiment 2

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Reviewed Marked as Reviewed by ChiomaBlessing on 2024-3-14

Curated date: 2024/03/14

Curator: ChiomaBlessing

Revision editor(s): ChiomaBlessing, Victoria

Differences from previous experiment shown

Subjects

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

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: Patients after the conditioning regimen, when the patient's bone marrow is intentionally depleted of cells, necessary for the success of the transplant

Group 1 sample size Number of subjects in the case (exposed) group: 30

Lab analysis

Statistical Analysis

Alpha Diversity

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

Simpson Estimator of species richness and species evenness: more weight on species evenness: decreased

Richness Number of species: decreased

Experiment 3

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Reviewed Marked as Reviewed by ChiomaBlessing on 2024-3-14

Curated date: 2024/03/14

Curator: ChiomaBlessing

Revision editor(s): ChiomaBlessing, Victoria

Differences from previous experiment shown

Subjects

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

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

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: Patients at the final phase of Allogeneic Hematopoietic Stem Cell transplant, when the new transplanted stem cells start to grow and produce new blood cells.