The oral microbiome of patients undergoing treatment for severe aplastic anemia: a pilot study

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Reviewed Marked as Reviewed by Atrayees on 2023-7-18
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
Authors
Ames NJ, Barb JJ, Ranucci A, Kim H, Mudra SE, Cashion AK, Townsley DM, Childs R, Paster BJ, Faller LL, Wallen GR
Journal
Annals of hematology
Year
2019
Keywords:
Immunosuppression and hematopoietic stem cell transplant, Oral microbiome, Tongue brushings
The microbiome, an intriguing component of the human body, composed of trillions of microorganisms, has prompted scientific exploration to identify and understand its function and role in health and disease. As associations between microbiome composition, disease, and symptoms accumulate, the future of medicine hinges upon a comprehensive knowledge of these microorganisms for patient care. The oral microbiome may provide valuable and efficient insight for predicting future changes in disease status, infection, or treatment course. The main aim of this pilot study was to characterize the oral microbiome in patients with severe aplastic anemia (SAA) during their therapeutic course. SAA is a hematologic disease characterized by bone marrow failure which if untreated is fatal. Treatment includes either hematopoietic stem cell transplantation (HSCT) or immunosuppressive therapy (IST). In this study, we examined the oral microbiome composition of 24 patients admitted to the National Institutes of Health (NIH) Clinical Center for experimental SAA treatment. Tongue brushings were collected to assess the effects of treatment on the oral microbiome. Twenty patients received standard IST (equine antithymocyte globulin and cyclosporine) plus eltrombopag. Four patients underwent HSCT. Oral specimens were obtained at three time points during treatment and clinical follow-up. Using a novel approach to 16S rRNA gene sequence analysis encompassing seven hypervariable regions, results demonstrated a predictable decrease in microbial diversity over time among the transplant patients. Linear discriminant analysis or LefSe reported a total of 14 statistically significant taxa (p < 0.05) across time points in the HSCT patients. One-way plots of relative abundance for two bacterial species (Haemophilus parainfluenzae and Rothia mucilaginosa) in the HSCT group, show the differences in abundance between time points. Only one bacterial species (Prevotella histicola) was noted in the IST group with a p value of 0.065. The patients receiving immunosuppressive therapy did not exhibit a clear change in diversity over time; however, patient-specific changes were noted. In addition, we compared our findings to tongue dorsum samples from healthy participants in the Human Microbiome Project (HMP) database and found among HSCT patients, approximately 35% of bacterial identifiers (N = 229) were unique to this study population and were not present in tongue dorsum specimens obtained from the HMP. Among IST-treated patients, 45% (N = 351) were unique to these patients and not identified by the HMP. Although antibiotic use may have likely influenced bacterial composition and diversity, some literature suggests a decreased impact of antimicrobials on the oral microbiome as compared to their effect on the gut microbiome. Future studies with larger sample sizes that focus on the oral microbiome and the effects of antibiotics in an immunosuppressed patient population may help establish these potential associations.

Experiment 1


Needs review

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): WikiWorks, Peace Sandy

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
Tongue Glossus,Tongue,tongue
Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Severe aplastic anemia SAA,Severe aplastic anemia,severe aplastic anemia
Group 0 name Corresponds to the control (unexposed) group for case-control studies
baseline
Group 1 name Corresponds to the case (exposed) group for case-control studies
hematopoietic stem cell transplantation engraftment
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
In HSCT patients, The first sample was obtained before transplant conditioning treatment. The second specimen was collected at engraftment, defined as two absolute neutrophil counts of greater than 500 per microliter for at least 2 days. The final specimen collection occurred at the participant’s scheduled clinic visit approximately 100 days following transplant.
Group 0 sample size Number of subjects in the control (unexposed) group
4
Group 1 sample size Number of subjects in the case (exposed) group
4

Lab analysis

Sequencing type
16S
16S variable region One or more hypervariable region(s) of the bacterial 16S gene
V2-V8
Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
Ion Torrent

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
relative abundances
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)?
No


Signature 1

Needs review

Curated date: 2021/01/10

Curator: Shaimaa Elsafoury

Revision editor(s): WikiWorks, Atrayees, Folakunmi

Source: figure 8a

Description: Statistically significant bacteria as determined by Lefse analysis for hematopoietic stem cell transplantation patients between the baseline timepoint and engraftment timepoint

Abundance in Group 1: increased abundance in hematopoietic stem cell transplantation engraftment

NCBI Quality ControlLinks
Haemophilus parainfluenzae
Rothia mucilaginosa
Actinomyces lingnae
Gemella sanguinis
Oribacterium sinus
Prevotella denticola
Gemella haemolysans
Neisseria
Fusobacterium periodonticum
Stomatobaculum
Hoylesella nanceiensis
Porphyromonas sp.

Revision editor(s): WikiWorks, Atrayees, Folakunmi

Experiment 2


Needs review

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): WikiWorks, Folakunmi, Victoria

Differences from previous experiment shown

Subjects

Lab analysis

16S variable region One or more hypervariable region(s) of the bacterial 16S gene
V3-V9

Statistical Analysis

Signature 1

Needs review

Curated date: 2021/01/10

Curator: Shaimaa Elsafoury

Revision editor(s): WikiWorks

Source: Figure 8&7

Description: Statistically significant bacteria as determined by Lefse analysis for (a) hematopoietic stem cell transplantation and (b) immunosuppressive therapy group.

Abundance in Group 1: decreased abundance in hematopoietic stem cell transplantation engraftment

NCBI Quality ControlLinks
Haemophilus parainfluenzae
Actinomyces lingnae
Gemella sanguinis
Oribacterium sinus
Neisseria
Hoylesella nanceiensis

Revision editor(s): WikiWorks

Experiment 3


Needs review

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): WikiWorks, Victoria

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
engraftment
Group 1 name Corresponds to the case (exposed) group for case-control studies
hematopoietic stem cell transplantation 100 days after the transplant

Lab analysis

16S variable region One or more hypervariable region(s) of the bacterial 16S gene
V2-V8

Statistical Analysis

Signature 1

Needs review

Curated date: 2021/01/10

Curator: Shaimaa Elsafoury

Revision editor(s): WikiWorks

Source: Figure 8&7

Description: Statistically significant bacteria as determined by Lefse analysis for (a) hematopoietic stem cell transplantation and (b) immunosuppressive therapy group.

Abundance in Group 1: increased abundance in hematopoietic stem cell transplantation 100 days after the transplant

NCBI Quality ControlLinks
Haemophilus parainfluenzae
Gemella sanguinis

Revision editor(s): WikiWorks

Experiment 4


Needs review

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): WikiWorks, Victoria

Differences from previous experiment shown

Subjects

Lab analysis

16S variable region One or more hypervariable region(s) of the bacterial 16S gene
V3-V9

Statistical Analysis

Signature 1

Needs review

Curated date: 2021/01/10

Curator: Shaimaa Elsafoury

Revision editor(s): WikiWorks

Source: Figure 8&7

Description: Statistically significant bacteria as determined by Lefse analysis for (a) hematopoietic stem cell transplantation and (b) immunosuppressive therapy group.

Abundance in Group 1: decreased abundance in hematopoietic stem cell transplantation 100 days after the transplant

NCBI Quality ControlLinks
Rothia mucilaginosa

Revision editor(s): WikiWorks